Jennifer LaRocco, an advocate and writer at CerebralPalsyGuidance.com, regularly shares insights and support for individuals and families affected by cerebral palsy. With a personal connection to the condition, she offers empathy, understanding, and valuable information through her articles. Jennifer’s dedication to raising awareness, promoting inclusivity, and providing practical guidance reflects her commitment to improving the lives of those navigating the challenges of cerebral palsy. Her contributions serve as a beacon of support for the community, offering hope, empowerment, and a sense of belonging to individuals facing similar experiences.
This is the seventh and last part of our series about the condition based on our patient booklet “Fast Facts for Patients: Non-small Cell Lung Cancer with KRAS Mutation”. This article delves into the role of clinical trials and questions to ask your doctor.
There are different types of clinical trials, looking into screening or diagnosis for instance. The trials that are sometimes of most interest to people already diagnosed with cancer are trials that test new treatments.
Phases of Clinical Trials
A new treatment must go through several phases of clinical trials to prove that it works better than existing treatment and can be adopted into routine care. A potential treatment will only move on to the next phase of research if it is safe and shows promise.
Phase 0 and I Trials
The earliest-phase trials are Phase 0 and Phase I. These are usually very small trials, involving 10–50 people. Their aim is to find out if a potential new treatment is safe, what the side effects are, and what happens to the treatment in the body (how your body gets rid of a drug, for example). Researchers may include a number of different cancer types in these early-phase trials.
Phase II Trials
Once a treatment is found to be relatively safe, a Phase II trial may take place. This is a medium-sized trial, usually of fewer than 100 people. Phase II trials usually focus on one or two cancer types that the treatment worked best for in earlier trials.
The aim of Phase II trials is to find out more about side effects and see how well a treatment works for specific types of cancer. Sometimes Phase II trials are randomized, but generally not (there is more about randomization in the section below on Phase III trials).
Phase III Trials
Phase III is the largest phase of a clinical trial and is most likely what people think of when they think about research. The aim is to test a new treatment against a treatment that is already in use to see which works better for a particular type and stage of cancer. But Phase III trials also collect more side-effect data and look at the quality of life of those having each treatment.
Usually, hundreds or even thousands of people take part in a Phase III trial, and they are often international. These trials are usually randomized. Randomized means that participants are put into two or more groups to compare the existing treatment and the new treatment. The groups have to be as similar as possible. You can’t choose which group you’re in, because that could affect the results.
Participants in Phase III trials are monitored by the researchers for a number of years afterwards. This is to see how well each treatment works in the long term – whether it stops an early cancer coming back or controls an advanced cancer for longer. Phase III trials often take several years to show a result.
Phase IV Trials
Phase IV trials are often referred to as ‘post-marketing studies’, and are conducted after a treatment is approved. These trials provide additional information on the treatment, including risks, benefits, and best use.
The Benefits and Risks of Taking Part in a Trial
A common reason people have for entering a clinical trial is that it may give them access to an experimental treatment. Many people also feel that they are giving something back and that by taking part they can help people with cancer in the future.
Remember, if you enter a randomized trial, you may or may not get the experimental treatment. You may not know which treatment you’re getting, as many randomized trials are ‘blinded’. Blinded means the doctors and researchers running the trial don’t know who is having which treatment. This information is kept secret (‘blinded’) until it’s time to analyze the results.
With any experimental treatment, there is no absolute guarantee of safety. Treatments are tested thoroughly before they are given to people. With each phase of research, more is learned about possible side effects. But the treatment won’t have been given to large numbers of people, and not all side effects may be fully known.
As well as treatment, trials can often mean that you have more tests and scans than usual. Some people feel this is a benefit – they are having more check-ups and so feel reassured. Others find it stressful. There may be travel involved too, back and forth to the treatment center, though some costs may be covered by the organizer of the trial. It’s worth thinking about the time commitment too, and the impact more tests may have on your well-being before you join a trial.
Trials often have very strict entry (eligibility) criteria. This is so they can make accurate comparisons between groups of participants.
You will only be able to enter trials that are suitable for you. Suitable trials are those looking into treatment for your type and stage of cancer. There may also be restrictions on entry for treatments you’ve had in the past or other medical conditions you might have.
You have to give your formal consent to take part in a trial. Before you sign, the researchers have a legal obligation to tell you about:
- the trial aims
- the treatments
- the potential benefits and risks, including side effects
- the tests and check-ups you’ll need
- how long you’ll have to come for follow-up appointments
- whether they will be keeping tissue or blood samples for future research.
They’ll give you a patient information sheet to take away with you, with all of this information written down.
You don’t have to decide immediately whether you’ll join or not. It’s important to say if you’d like some time to think it over, and maybe talk things over with those closest to you. Ask if there’s a number you can call if you have further questions about participating.
Please don’t feel obliged to enter a trial. If you don’t, your doctor won’t be offended or upset, and it won’t affect your current treatment. And it’s important to know that you can withdraw from (leave) a trial whenever you want. You don’t have to give a reason.
How to Find Out about Clinical Trials
The easiest way to find out about clinical trials is to ask your own specialist. They have access to all of your test results and past treatments, so they can tell you which trials are suitable for you (and which you are likely to be eligible for).
Depending on where you live, you may also be able to find clinical trials online. There are cancer clinical trials databases based in the UK, Europe, and the USA.
The US National Library of Medicine (NLM) runs a clinical trials database that has information on trials running worldwide. It isn’t written for patients, so it can be difficult to understand. But you can search specifically for NSCLC trials and by country.
The European Union Drug Regulating Authorities Clinical Trials Database is the European database for all interventional clinical trials on medicinal products taking place in the European Union/European Economic Area. Again, this isn’t written for the public, so it can be difficult to read.
Cancer Research UK has a clinical trials database that is written specifically for the public, in plain English. It only lists trials that are active in the UK (but of course this does include some international trials). You can search for NSCLC trials, by trial phase, and for trials in England, Scotland, Wales, or Northern Ireland.
What to Ask about a Clinical Trial
If you are considering taking part in a clinical trial, it may be helpful to think through what you’d like to know before you join.
As well as finding out about the trial aims and treatments, there are practical concerns, such as how much time you’ll need to spend having tests, treatment, and check-ups. There may be hidden costs, such as parking and hotel stays. Ask if any financial support is available to help with these.
Questions for Your Doctor about Clinical Trials
- Are there any trials I could enter that are for my type and stage of cancer?
- What treatment can you offer if I decide not to enter a trial?
- What do the researchers hope to find out from this trial?
- What are the possible advantages and risks of taking part?
- Is the trial randomized?
- What will I have to do if I join the trial, including tests and check-ups?
- Can I have tests and treatment at my usual treatment center or will I have to travel?
- Is there any help available to cover costs?
- Will joining a trial mean that there are any medicines or treatments I can’t have?
- Is the trial insured?
- Will taking part in a trial affect my medical insurance?
Information based on Fast Facts for Patients: Non-small Cell Lung Cancer with KRAS Mutation (Karger, 2023).
This is the sixth part of our series about the condition based on our patient booklet “Fast Facts for Patients: Non-small Cell Lung Cancer with KRAS Mutation”. This article deals with how to talk to your doctor about your treatment and about finding further information and support.
Talking to Your Doctor about Your Treatment
The reason a doctor suggests a new treatment for advanced cancer is often because the treatment you’re on is no longer helping. This can be devastating to hear. It’s common for people to focus on it so much that they don’t hear anything else that’s said.
It may be more helpful to talk about any new treatment options at another appointment, when you’ve had time to sort out what you’d like to ask.
It’s a good idea to make a plan for the appointment by listing the questions you have. If you know you will be discussing something new with your doctor, it can help to take someone with you. They may pick up on things that you miss and vice versa.
Some doctors are happy for you to record consultations – but ask for permission first.
Your doctor has spent many years studying cancer care, and cancer is complicated. If you don’t understand something, ask your doctor to explain in a different way. You don’t have to know or use technical terms – but there is a guide to words and phrases in the back of this booklet if you want to know what they mean.
If you’re not eligible for current KRAS-targeted treatment, you may be eligible to participate in a clinical trial. If you’re interested, ask your doctor for more details.
Questions for Your Doctor about KRAS-Targeted Therapy
If you’re eligible for current KRAS-targeted therapy, questions for your doctor may include:
- What are the aims of this treatment?
- How do I take the treatment?
- How many times a day do I take it?
- Can I take the treatment at home?
- Can I continue to take other prescribed medicines?
- What should I do if I miss a dose?
- What should I do if I am sick after taking a dose?
- For how long will I take the treatment?
- What should I do if I have difficulty swallowing it?
- What are the most common side effects?
- How will I be monitored when I am on the treatment?
Finding Further Information and Support
It can be difficult to cope when you have an advanced cancer. But you don’t have to do it all alone. There may be times when you need the support of others. There are some steps you can take to try to make sure you have all the support you need.
Find Out about NSCLC and Its Treatment
People vary in how much they want to know when they have a life-threatening illness. Some people want to know everything, while others want to hear as little as possible about their illness or treatment. It’s completely up to you.
Being informed about your condition may help you to deal with it. It may give you back a sense of control. The more you know about a situation, the less scary it may seem. And, by being better placed to make decisions about your own treatment, you will be more in control.
You may also get more out of your consultations with your doctors and nurses. If you understand your condition and treatment, it may help you to communicate most effectively with them. And do ask for more explanation if there’s anything that’s not clear to you.
Share with Your Family and Friends
It’s often said that people don’t know what to say when someone close to them has cancer. That can be true. But most people are willing to talk about it – or better still, listen. They may not know whether you want to talk and are waiting for you to bring it up.
Of course, it’s entirely your choice who you tell and what you tell them. But sharing what you know and how you feel with your family and friends may help them to cope and to better support you. Tell them you don’t expect them to have answers, but that it helps to have someone to listen if you’re coming to an important decision.
Find Others in a Similar Situation
Finding others in a similar situation to you can be an important source of psychological support. Your specialist nurse may know of local support or patient advocacy groups that you can go to.
Local face-to-face support groups are usually for people with all types of cancer so you may not find people in exactly the same situation, but there are likely to be other people who’ve been told they have an advanced cancer, so they’ll have some idea of what it’s been like for you.
With online forums, finding other people with the same condition as you is easier than it used to be. A lot of people prefer to make contact online because it’s anonymous and can feel safe – you’re not so exposed. There are some details at the back of this booklet about support organizations you may find helpful.
Second Opinions
As we’ve said, your own specialist is best placed to advise you on treatment because they know you so well. However, it’s understandable to want to check that what you’ve been told about your situation is correct.
Most cancer specialists are used to people asking for a second opinion. They understand that you are not questioning their judgement but want to explore every avenue.
If you feel awkward asking your current specialist, you can ask your primary care (general) practitioner. If you are making a private approach to a cancer specialist, you may be able to make an appointment yourself. But it’s best to involve your specialist if you can. They will let the doctor providing the second opinion have access to all your scans and test results. If this isn’t possible, you may need to have some repeated.
Information based on Fast Facts for Patients: Non-small Cell Lung Cancer with KRAS Mutation (Karger, 2023).
This is the fifth part of our series about the condition based on our patient booklet “Fast Facts for Patients: Non-small Cell Lung Cancer with KRAS Mutation”. This article explains KRAS-targeted therapies and how they work in non-small cell lung cancer (NSCLC).
If you have an NSCLC that has a KRAS mutation, this information will tell your doctor which treatment option is likely to work best for you. This section tells you more about KRAS-targeted treatment and other treatment options that are in development for KRAS-positive NSCLC.
KRAS-Targeted Therapies
At the time of writing there are two KRAS-targeted therapies that are approved for treating NSCLCs with a G12C KRAS mutation. These therapies are sotorasib and adagrasib. To have this treatment, you must have:
- an NSCLC with the G12C KRAS mutation
- cancer that has spread from the lung into nearby body tissues or to somewhere else in the body
- already tried at least one other type of ‘systemic’ treatment for your cancer spread (such as chemotherapy or immunotherapy).
Treatments that target other less-common types of KRAS mutations are also being researched. There are also ‘universal’ KRAS-targeted therapies in development. These may work across several different types of KRAS mutation. If you don’t have a G12C mutation in your lung cancer cells, your doctor may suggest having one of these treatments as part of a clinical trial.
How KRAS-Targeted Treatment Works
To understand how this type of treatment works, it may help to think of it as a switch that turns off the cancer’s ability to grow.
As we’ve seen, the cancer cells produce an abnormal form of the KRAS protein. This permanently switches on the cells’ drive to divide and multiply, causing the cancer to grow.
KRAS-targeted treatment acts as a block on the abnormal protein. It attaches (binds) to it and stops it from delivering the message telling the cancer cells to divide.
Commonly Used Words
You may hear your doctor talk about systemic therapy.
A systemic therapy is one that circulates through the bloodstream and treats cancer wherever it is in the body. Any treatment you take as a tablet or have through a drip (IV [intravenous] infusion) into a vein is systemic.
In cancer care, chemotherapy, hormone therapy, immunotherapy, and targeted therapies given by mouth or by injection are called ‘systemic’.
Cancers that have spread are generally treated with systemic therapies because they can reach the cancer cells wherever they are in the body.
How KRAS-Targeted Treatment Is Helping
Before treatments were developed, people with KRAS-positive advanced NSCLC didn’t do as well as those without a KRAS mutation in their tumors. But KRAS-targeted treatment may change that.
Clinical trials have looked at treating advanced NSCLC with the G12C mutation. More than 1 in 3 (33%) patients who participated in the trials had their cancer shrink or stop growing for a few months. These were early Phase I and II trials. Research is ongoing in later-phase randomized trials.
Sadly, we know that the treatment currently available will not permanently stop advanced lung cancer from growing. In these trials, the treatment controlled advanced disease for approximately 6 to 7 months.
Important: Statistics apply to the overall population of trial participants and can’t predict what will happen in your case. They can only be a general guide to what may help you. It’s best to discuss this with your own specialist, who has all the test results that apply to you.
Trials are now looking into whether KRAS-targeted therapy may help when combined with other types of treatment, such as chemotherapy or immunotherapy.
So far, we only know that KRAS-targeting treatments can help with advanced disease. But now researchers are starting to look into whether the treatment could help people with early-stage lung cancer.
KRAS Vaccines and Genetic Engineering
Researchers are currently looking into creating vaccines that target KRAS mutations in people with advanced lung cancer and at modifying a patient’s own immune system cells to help them target cancer cells. Both these types of treatment are still in the early stages of research.
Information based on Fast Facts for Patients: Non-small Cell Lung Cancer with KRAS Mutation (Karger, 2023).
This is the fourth part of our series about the condition based on our patient booklet “Fast Facts for Patients: Non-small Cell Lung Cancer with KRAS Mutation”. This article shows how your doctor knows your cancer is KRAS-positive and gives more information on KRAS in non-small cell lung cancer (NSCLC).
How Your Doctor Knows Your Cancer Is KRAS-Positive
To find out if your cancer is KRAS-positive, your doctor took a sample of cancer cells for testing (a biopsy). You may have had this done when you were first diagnosed, through a bronchoscopy or a needle biopsy. Or the cells may have been tested when you had surgery to remove your primary cancer.
Mutations can change in cancers as they grow, so your doctor may have re-tested your cancer cells. You may have had a blood test to do this, as genetic material from the cancer can in some cases be detected in blood samples. Your doctor may call this a ‘liquid biopsy’. Or you may have had a sample of secondary cancer taken, for example through a liver biopsy or a lymph-node biopsy.
More about KRAS
KRAS and its importance in the development of cancers was discovered over 30 years ago. It was first found in human cancer cells in the early 1980s. Soon, scientists had identified KRAS mutations in a whole range of cancers and realized its importance. They now calculate that some type of KRAS mutation is found in more than 1 in 5 (20%) of all cancers. Around 1 in 4 (25%) NSCLCs have KRAS mutations.
KRAS is associated with some cancer types more than others. KRAS mutations are nearly always found in adenocarcinomas (cancers that develop from gland cells in the lung). They are also more common in:
- people who are or were tobacco smokers
- people who were exposed to asbestos in the past
- some ethnic groups compared with others: for example, they are found in up to 1 in 2 (50%) lung cancers diagnosed in White populations compared with 1 in 6 (around 17%) diagnosed in populations with lung cancer from Asia.
KRAS Subtypes in NSCLC
We now know that there are different types of KRAS mutations. These are named after the point in the gene where the mutation occurs and the change that takes place. As you can see, the G12C mutation is much more common than the others. The mutation occurs at position 12 in the KRAS gene and the amino acid C (cysteine) is substituted for the G (glycine) amino acid. Amino acids link together to form proteins.
Treatments are being developed by several pharmaceutical companies that specifically target this mutation. Other treatments are being developed that hopefully will work for several types of KRAS mutation. Ask your specialist what type of mutations they’ve found in your lung cancer cells. It’ll help you to understand which treatments may help.
Questions for Your Doctor on Lung Cancer Mutation(s)
- Have any mutations been found in my lung cancer cells?
- What are the implications of the mutation(s) for my lung cancer?
- Is there any treatment that targets the lung cancer mutation(s) I have?
Information based on Fast Facts for Patients: Non-small Cell Lung Cancer with KRAS Mutation (Karger, 2023).
Chronic lymphocytic leukemia (CLL) is a slow-growing type of blood cancer and the most common form of leukemia in adults. If you or a loved one is affected by CLL, the book “Fast Facts for Patients: Chronic Lymphocytic Leukemia” by Kathryn Huntley, Professor Anna Schuh, and Dr Alessandra Tedeschi is your go-to resource.
September 1 is World CLL Day. In 2023 the focus lies on mental health. To learn more about the condition, the awareness day and its theme, visit the CLL Advocates Network.
We asked Leanne Kennedy, who contributed to the booklet, about the impact of CLL on mental health. These are her thoughts:
“Silence the mind to hear the heart.”
These words resonated with me as I find I need to silence my mind from negative self-defeating thoughts to find peace and quiet. I know it is natural and healthy to allow yourself to feel sad and worried whilst coming to terms with all the twists and turns of the CLL journey, from being diagnosed to watch and wait, treatment and then fear around remission. For me, though, I realised that if I stay in that sad and worried state of mind for too long, I go into a ‘why bother’ state of mind which is a miserable and sometimes harmful place to be. After experiencing this throughout my journey I am aware that if I try to look after my mental, physical and spiritual well-being – whether that be going for a walk and enjoying nature, eating well, doing activities that I enjoy or simply reaching out to a friend or family – that any positive and kind thing I can do for myself propels me into a happier, healthier me. My brother shared a beautiful quote with me the other day:
“We have two lives, and the second begins when we realize we only have one.” (Confucius)
This is the third part of our series about the condition based on our patient booklet “Fast Facts for Patients: Non-small Cell Lung Cancer with KRAS Mutation”. This article explains the role of genes, oncogenes, driver mutations and biomarkers in non-small cell lung cancer (NSCLC).
More about Genes and Cancer
Cancer treatment has been developing over the past few decades. Genes can become abnormal, enabling cancers to grow and spread; researchers are now finding ways to target these abnormal genes. To understand this type of treatment, which is often referred to as ‘targeted treatment’, it helps to understand a bit about how cancers start.
Everything that cells do starts with their genes, which are made of DNA and carry instructions for making proteins. Normal cells need these proteins to work properly. Proteins control how cells grow and become specialized, as well as controlling every function of each cell.
Gene Mutations and Cancer
Cells can become cancerous because they have changes (mutations) in their genes. Some mutations are inherited from a parent, are present from birth, and can be passed on to children. Others develop during a person’s lifetime and can’t be passed on.
Mutations cause the affected genes to make abnormal proteins that can prevent the cell from working properly. Not all mutations result in a cancer. But some give the cell properties that make it more likely to become cancerous if it collects a few more mutations.
The most obvious cancer-causing mutations are those that cause the cell to keep multiplying when it shouldn’t. Normally in adults, most cells only reproduce to replace worn-out cells and repair damage. But cancer cells carry on multiplying much more quickly than normal cells do. The excess cells form a lump – a tumor.
There are other mutations that mean the cells lose their ability to stick together. This is one reason why cancers are able to spread. Cancer cells can break away and travel through the blood and lymphatic system to another part of the body and start growing there. Once a cell has a mutation, it will pass it on every time it divides.
Oncogenes and Cancer
Mutated forms of genes involved in normal cell division are called oncogenes. They can encourage cancer growth and development.
Sometimes oncogene mutations that lead to cancer are inherited – the breast cancer genes BRCA1 and BRCA2, for instance. More commonly, mutations happen because of cancer-causing substances we’re exposed to, such as ultraviolet rays from the sun or smoking tobacco. These mutations are only found in cells that have become damaged. So, if you’re told your lung cancer has a mutation in the KRAS oncogene, this mutation is only in the lung cancer cells. You weren’t born with the mutation, it isn’t in any of the other cells of your body, and you can’t pass it on to your children.
Other Types of Cancer-Causing Gene Mutations
As well as oncogenes, there are other types of genes that contribute to cancer growth and development. One group is called tumor suppressor genes. The normal function of these genes is to stop cells from dividing when they shouldn’t. In many tumors, however, mutations in these genes mean they are lost or inactivated. This allows the cells to continue to divide and the cancer develops.
Other cancer-causing genes are called DNA repair genes. In normal cells, these genes repair damage caused to the DNA. If the DNA damage is too bad, the DNA repair gene will tell the cell to self-destruct.
Cells with mutations in these DNA repair genes are less able to repair cancer-causing mutations. They are also able to survive with DNA damage that would cause normal cells to die.
Driver Mutations
The most important gene changes in the development of cancer cells are called driver mutations – because they drive the development of a cancer. An abnormal protein produced because of a driver mutation may be key to encouraging cancer cells to keep on dividing, for example.
These important mutations are being researched as potential targets for treatment. If treatments can block the proteins that these genes make, they can help to stop cancer growth and might keep people healthy for longer.
KRAS Mutations Are Driver Mutations
Normal KRAS protein is important in the control of cell replacement and development. But KRAS mutations can produce abnormal proteins that are permanently active, instead of only working when they need to. These proteins encourage cells to multiply all the time.
There are several different mutations in the KRAS gene that we know are possible driver mutations for lung cancer. Each individual cancer is likely to have only one type of driver mutation.
Driver Mutations and Biomarkers
A biomarker is a characteristic of the body that can be measured. There are different types of biomarkers. For instance, a biomarker may be used to diagnose a disease, measure a normal body process, or show how a treatment is working.
If a diagnostic biomarker is present, that confirms a diagnosis. Some biomarkers are used to monitor a condition. For example, excess PSA is made by prostate cancer cells, so levels rise when a prostate cancer is growing.
Types of Question that Can Sometimes Be Answered by Cancer Biomarkers
- Prognostic: How aggressive is the cancer likely to be?
- Diagnostic: What type of cancer is it?
- Predictive: Is this the optimal drug for my cancer?
- Recurrence: Will the cancer return?
Driver mutations can also be biomarkers. If a treatment has been developed that targets a driver mutation, the presence of the abnormal protein produced as a result of the mutation in your cancer cells shows your doctor that this type of treatment could work for you. But not all cancers have a specific driver mutation.
Biomarkers in Lung Cancer
There are several different biomarkers in lung cancer. The most common include EGFR, ALK, and KRAS.
- EGFR is a gene that normally encourages cells to divide. But if mutated, it causes too much cell division, which can result in a cancer. There are several different EGFR mutations that can lead to lung cancer. Some of these can be targets for treatments called EGFR inhibitors.
- ALK is a gene that normally helps in the development of the gut and nervous system, and is switched off after this is completed in the womb. Sometimes ALK gets switched back on again, fuses with another gene, and causes lung cancer. Treatments that target ALK are called ALK inhibitors.
- KRAS is the biomarker that we’re most interested in here. You’ve been given this booklet because your lung cancer has tested positive for a specific KRAS mutation and might respond to treatment that blocks the abnormal protein made by it.
Information based on Fast Facts for Patients: Non-small Cell Lung Cancer with KRAS Mutation (Karger, 2023).
This is the second part of our series about the condition based on our patient booklet “Fast Facts for Patients: Non-small Cell Lung Cancer with KRAS Mutation”. This article provides details on what metastatic non-small cell lung cancer (NSCLC) is.
Metastatic cancer (also known as ‘advanced cancer’) means that a cancer has spread from where it first started in the body. A metastatic lung cancer is one that has spread from the lung to another body organ. The cancer cells do this by breaking away from the tumor and traveling through the bloodstream or the lymphatic system. The cells settle somewhere else and start to grow into new tumors.
Primary and Secondary Cancer
Where the cancer starts is called the primary cancer. Where the cancer spreads to is called a secondary cancer.
NSCLC can spread to several places, such as the bones, liver, and brain. Because the cells that have spread are lung cancer cells, it’s still a lung cancer, not a liver or bone cancer. It’s important to understand this. Because these secondary cancers are made of lung cancer cells, they will respond best to treatment that has been proven to treat lung cancer, not primary liver cancer or primary bone cancer.
Sometimes cancers aren’t found until they’ve already spread. A primary cancer may be small and cause few or no symptoms. But if cells have broken away from the main tumor and started to grow elsewhere, these secondary cancers may cause symptoms that lead to diagnosis.
Finding Out That You Have Metastatic Cancer
It’s a shock to find out a cancer has spread. Whether it’s come back after earlier treatment for a primary cancer or had already spread when you were diagnosed, it’s difficult news to hear. It’s also difficult news to pass on to your close friends and family.
People may tell you to ‘keep positive’ or even that ‘being positive will help fight your cancer’. But there’s no right or wrong way to feel. You don’t have to keep up a cheerful front all the time. You can have a positive attitude and still feel worried or upset.
Reliable sources of support and information are important. It may help to talk to others in the same situation as you. The internet makes this easier than ever. There are also likely to be local support groups where you can meet other people affected by cancer. Ask at your cancer center. You can also ask your healthcare team about available mental health/counseling resources, care giver support, or financial planning help.
Positivity also means being hopeful. New treatments are being developed all the time. In fact, that’s what this booklet is about. There are now more treatments for metastatic lung cancer than ever before. Even if it’s not possible to completely get rid of your cancer, there are treatments that might control it.
Your family and friends will want to support you, even if they are worried and not sure how best to do it. Let them know what you need. Just listening to you while you talk through concerns can be a great help.
Commonly Used Words
There are lots of different terms that doctors use about cancer, and it helps to know what they mean.
The primary cancer site is where the cancer first started growing in the body. With NSCLC, the primary cancer site is the lung.
A secondary cancer site is where a primary cancer has spread to. It’s the same type of cancer as the primary cancer, just growing somewhere else in the body.
Metastatic cancer (sometimes called mets) means a cancer that has spread to another part of the body.
You may hear your doctor talk about staging. This is how doctors describe how far a cancer has grown and whether it has spread. There are usually four main cancer stages. A small, localized cancer is stage 1. A stage 4 cancer means the same as metastatic cancer – a cancer that has spread to another part of the body.
Information based on Fast Facts for Patients: Non-small Cell Lung Cancer with KRAS Mutation (Karger, 2023).
This is the first part of our series about the condition based on our patient booklet “Fast Facts for Patients: Non-small Cell Lung Cancer with KRAS Mutation”. This article explains what non-small cell lung cancer (NSCLC) is and how lung cancer can develop.
First, the Facts
- Non-small cell lung cancer (NSCLC) is one of two main types of lung cancer.
- Some lung cancers spread to other parts of the body before they are diagnosed. A cancer that has spread is called ‘metastatic’.
- New lung cancer treatments are being developed that directly target the gene mutations that control how cancers grow and spread.
- The most important gene mutations in cancer are called ‘driver mutations’. In NSCLC, this includes KRAS mutations, which can be used as targets for treatment.
- There are new treatments designed for lung cancers with a KRAS mutation that are already available. And more are being developed.
- Treatments in development are tested in clinical trials. There are several different phases of clinical trials that people with cancer can take part in.
What Is Non-Small Cell Lung Cancer?
Non-small cell lung cancer – abbreviated to NSCLC – is one of the two main types of lung cancer; 85% of lung cancers are NSCLC, the other 15% are called small cell lung cancers.
There are three main types of NSCLC that develop from different types of lung cells.
Adenocarcinoma develops from gland cells in the lungs, which produce mucus. The mucus helps to trap any irritants that get into your airways so you can get rid of them by coughing. Around 4 in 10 lung cancers (40%) are this type.
Squamous cell carcinoma develops from flat cells that line the inside of the airways of the lungs. Around 3 in 10 lung cancers (30%) are this type.
Large cell carcinoma usually develops in the outer area of the lungs. It’s called that because the cancer cells look particularly large under a microscope. These cancers are sometimes called ‘undifferentiated’. That means the cells are not specialized as normal lung cells are. About 1 in 10 lung cancers (10%) are this type.
There are other subtypes of NSCLC that are much rarer. Together, they make up about 1 in 20 cases (5%).
How Can Lung Cancer Develop?
We can’t tell exactly what causes each case of lung cancer. But there are risk factors we do know about.
Tobacco smoke is the main risk factor for lung cancer, causing about 8 out of 10 cases (80%).
Some people get lung cancer because of substances they’ve been exposed to. Asbestos – a fibre used for insulation – is a severe lung irritant that can cause cancer many years later. It’s now banned in many countries, but people working in the building industry may come into contact with it. Silica and diesel exhaust fumes are other workplace risk factors.
Air pollution can cause lung cancer. The risk varies, depending on the levels of pollution where you live and work.
There is radiation that occurs naturally in rocks, water, and air, as well as cosmic radiation that comes from space. Radon gas is produced by the natural decay of uranium. Levels are higher in some areas than others and can increase the risk of lung cancer, particularly for people with a history of smoking.
Why Do Some People Get Cancer and Not Others?
Everyone is at risk of developing lung cancer, irrespective of their smoking history. However, smoking can interact with other factors and increase your risk. Some people are more prone to cancer than others, particularly if there are other cases in their close family.
Some cancers occur randomly, and we never know the cause. And some may be due to risk factors we don’t know about yet.
Information based on Fast Facts for Patients: Non-small Cell Lung Cancer with KRAS Mutation (Karger, 2023).
This is the seventh and last part of our series about the condition based on our patient booklet “Fast Facts for Patients: Beta Thalassemia”. This article offers information on how to live with beta thalassemia (BT) and about asking for help.
Living with Beta Thalassemia
Getting a diagnosis of BT – whether for yourself or your child – can be a shock, even if you know BT is in your family background. You are likely to have a lot of questions. It’s important to find out as much as you can about BT and about your own situation.
To do that, it’s best to talk to a knowledgeable healthcare professional or use other trusted sources of information about BT. Genetic counseling can also help you to understand your condition and its implications.
It can be difficult to know which websites on BT are accurate and have up-to-date information.
BT is complicated so it’s easy to get confused. It may help to write down a list of the things you need to know or questions you want to ask and take it to your doctor’s appointment. It may also help to take someone with you, so you can compare notes afterwards.
Treatment is improving all the time for BT. Many children born with the condition are now expected to have a normal life span, and there are things you can do to help yourself stay as healthy as possible.
Have Treatment When You Need It
The best way to avoid complications is to stick to any treatment schedules and go to all your check-up appointments.
Important: Contact your doctor promptly if you have any signs of infection or other illness and make sure you keep your vaccinations up to date – especially if you’ve had your spleen removed.
Your Diet
When you have thalassemia you may have low levels of some vitamins and minerals, such as vitamin C, zinc, folic acid and vitamin D. This is partly because of the anemia and partly because of high iron levels and the treatment used to remove iron. Your doctor may check your levels and give you supplements of anything that you’re lacking.
Some doctors suggest avoiding foods that contain lots of iron and some think that this has little effect in preventing iron overload. It may be useful to check the iron content of packaged foods and medications and, in case of doubt, ask your healthcare team for advice.
It’s always best to discuss your diet with your BT healthcare team.
Keep Fit for Healthy Bones
Regular physical exercise has many benefits. It can improve your mood and help strengthen your bones. Alcohol and smoking are best avoided.
Asking for Help
Do ask questions and tell your healthcare team about anything that’s concerning you. They know how complex BT is and won’t mind, even if you ask the same questions more than once.
Questions for Your Doctor
- I’ve been told I’m a carrier of a BT gene – what are the implications for me and for my children?
- What is the likelihood of me having a/another child with BT?
- Is there anything that can be done to reduce the risk of having a child with BT?
- What type of BT do I/does my child have?
- What impact will BT have on me/my child?
- Are there any particular warning signs I need to be aware of at home?
- Will I/they need regular treatment?
- Will my/their need for treatment change as I/they get older?
- What are the likely side effects of treatment?
- What complications could there be and how likely are they?
- Will my child with BT be able to have children and what do they need to know beforehand?
Information based on Fast Facts for Patients: Beta Thalassemia (Karger, 2023).
This is the sixth part of our series about the condition based on our patient booklet “Fast Facts for Patients: Beta Thalassemia”. This article lists new treatment developments as well as new treatments for beta thalassemia (BT).
New Treatment Developments
If you are interested in new treatments, you may want to ask your doctor about clinical trials. A new treatment must go through several phases of testing before it can be proven to work better than existing treatment and be adopted into routine care. A potential treatment will only move on to the next phase of research if it is safe and shows promise.
Clinical Trial Phases
The first phase of testing – phase I – is to make sure a new treatment is safe, find out about its side effects and decide the best dosage. These trials are usually small, with only a few people in each one.
- Phase II trials are larger and find out whether a new treatment is likely to work for a particular medical condition.
- Phase III trials test the new treatment against the standard existing treatment to see which works best. These are the largest trials and are often international, particularly for rare conditions.
- Phase III trials have to be randomized. In randomized trials, patients are put into different groups. A computer is used to decide who is in which group. You cannot choose which group you are in and so some people will not take the new treatment. Randomizing means that the researchers can be more sure that differences in the results at the end of the trial are caused by the treatment being tested.
New Treatments for Beta Thalassemia
There are a few new treatments being tested for BT:
- gene therapy
- treatment to improve red blood cell health and function
- treatment to reduce iron absorption.
Gene Therapy
This type of treatment is showing promising results in treating BT. Scientists take some of your own blood stem cells and insert a Hb gene into them in the laboratory. You then have treatment to destroy your bone marrow cells, before you have the engineered stem cells put back into your bloodstream through a drip.
The process is very similar to having a SCT from a donor, except that your own cells are used. This means the treatment is possible for people who don’t have a donor.
Like having a SCT, gene therapy isn’t easy treatment to get through. You need to have chemotherapy, with all the side effects that brings. However, after the procedure you won’t have to take drugs to damp down your immune system as you’ve had your own blood stem cells and not cells from someone else.
Several trials of gene therapy have been carried out in people with transfusion-dependent BT and other trials are continuing.
A gene therapy was approved in 2022 in the US for people with transfusion-dependent BT.
Improving Red Blood Cell Health
Clinical trials are looking into treating anemia with medication to improve the health, function and survival of red blood cells. In BT, it may mean you don’t need transfusions so often.
Mitapivat is a new treatment that is being tested in people with alpha thalassemia or BT. It’s a tablet that you take twice a day. It’s already used to treat another genetic condition, called pyruvate kinase deficiency.
Mitapivat increases the level of an enzyme that red blood cells need to function properly. This enzyme is low in thalassemic red blood cells.
Early trial results show that mitapivat may help to reduce anemia in people with BT who don’t need regular blood transfusions. Side effects found so far include difficulty sleeping, headache and dizziness.
Mitapivat is being tested in phase III trials for people with BT who don’t need regular transfusions, as well as those who do.
Reducing Iron Absorption
Researchers have identified a natural body hormone called hepcidin that reduces the absorption of iron from the digestive system and helps regulate iron levels in the body. Early trials used drugs that mimic hepcidin. These showed positive effects on iron levels in BT and also on red blood cell production.
A more recent approach uses treatments that target the main regulators of hepcidin. The first clinical trials of these treatments are under way.
Information based on Fast Facts for Patients: Beta Thalassemia (Karger, 2023).
This is the fifth part of our series about the condition based on our patient booklet “Fast Facts for Patients: Beta Thalassemia”. This article gives an overview of the treatment options for beta thalassemia (BT).
BT is complex and needs specialist care. Your treatment should be managed at a specialist center for blood disorders and overseen by a doctor with experience in these diseases.
Specialist centers will often have a thalassemia clinical nurse specialist who you can contact if you have any queries when you’re at home. Some centers also have psychologists and social workers who are familiar with the issues that BT can cause.
The two main treatments for BT are:
- blood transfusions to combat anemia and associated complications
- chelation therapy to control iron overload.
You may also receive:
- treatment for complications, such as an enlarged spleen and gallstones
- medication to improve the production of red blood cells
- stem cell transplant – an intensive treatment that is a potential cure for BT.
What treatment you have will depend on a number of things, including whether your BT is transfusion dependent or non-transfusion dependent.
Non-Transfusion-Dependent Beta Thalassemia
You won’t need regular blood transfusions if your bone marrow is making enough Hb for you to have a good quality of life and a low risk of disease-related complications. But this can change with time. As you get older, you may need to have transfusions more often. With any added physical stress, such as infection or pregnancy, you are also more likely to need a top-up of red blood cells from a transfusion.
Iron can build up in your body even if you don’t have regular transfusions. Your doctor will monitor your iron levels and treat any overload as necessary.
Transfusion-Dependent Beta Thalassemia
If your BT is transfusion dependent, you need lifelong treatment with blood transfusions to correct serious anemia and prevent disease-related complications. You will also need chelation therapy to keep your iron levels within safe limits. Having this treatment regularly is vital for preventing complications and ensuring normal growth, development and lifespan.
If your spleen becomes enlarged and hyperactive, your doctor may suggest removing it. But they will try to avoid surgery if at all possible. There are important long-term side effects associated with removing your spleen.
Stem cell transplant is now a possible cure for BT. But it is very intensive treatment and is only considered for BT major.
Blood Transfusions
Blood transfusions top up your levels of normal healthy Hb. How often you need blood transfusions will depend on your Hb level. Your doctors will want to keep this high enough to:
- prevent severe anemia
- allow normal growth and development
- prevent the bone changes associated with BT.
If you have transfusion-dependent BT, you may need blood as often as every 2–4 weeks. The number of units of blood you will need depends on your body size. Your Hb level is a better guide for your treatment than the time since your last transfusion.
The blood you receive is carefully matched specifically for you, so that you don’t have a reaction to the donor’s red cells.
Chelation Therapy
As explained in the iron overload section, iron can build up in your body if you have BT. Too much iron is toxic so you will need iron chelation therapy to remove it.
Your doctor will monitor your iron levels with regular blood tests. If your levels seem high, you may have an MRI scan to measure the iron concentration in your heart and liver. This will show whether you need to start chelation therapy.
If you have regular transfusions for your BT, you’ll need to start iron chelation therapy after you’ve had 10–20 units of blood. It is very important for your health to follow your doctor’s instructions about iron chelation therapy.
Your doctor will prescribe an iron chelating medicine for you. There are three different drugs available for chelation therapy. Two of them are available as oral medication and can be taken daily by mouth. One is a daily injection under the skin or it can be given through a drip (intravenous infusion or IVI). Sometimes, doctors prescribe two iron chelators in combination.
Stem Cell Transplant
There is now a potential cure for BT, called stem cell transplant (SCT). This is intensive treatment that isn’t available everywhere. Your doctor will carefully consider the decision to undertake SCT as the procedure has side effects, some of which can be life threatening. In the past SCT was reserved for younger children with BT. Today, young adults whose BT is well controlled are also considered for transplant.
Stem cells are cells in the bone marrow that are capable of developing into all the different types of blood cell, including red cells. In a transplant, the stem cells in your bone marrow are destroyed to make room for healthy cells from a donor. The donor has to be someone whose blood cells closely match yours, and this is usually a close family member. If you do not have a family member whose blood cells match yours, it is possible to search for an appropriate donor in bone marrow donor registries. Your doctor will need to find someone who is not related to you, but whose cells are a close match for yours.
The aim of SCT is that the donor stem cells will start to grow inside your bones and provide new blood stem cells to replace yours. This process is called ‘engraftment’. The new stem cells will be able to make all the different types of blood cells you need, including healthy red cells.
The chemotherapy you have as part of your transplant increases your risk of infection. You will need to be nursed in complete isolation for some time after having your stem cell infusion. Other side effects of SCT include hair loss, sore mouth, sickness, diarrhea, bruising, bleeding and infertility.
For some months after the procedure, you will need to take drugs to lower the activity of your immune system (this is called ‘immunosuppression’). This reduces the risk of your own cells attacking the ones from your donor. Doctors call this ‘rejection’.
Stimulating the Production of Red Blood Cells
A medicine called luspatercept has been approved in Europe, the USA, Australia and many other countries, to treat adults with transfusion-dependent BT.
Luspatercept helps red blood cells to develop better in the bone marrow and so reduces the need for transfusions in BT. Some patients who were previously transfusion dependent may even be able to manage without further blood transfusions.
You have luspatercept as a small injection under the skin (subcutaneously) every 3 weeks. Some people have side effects, including headache and bone pain. Your doctor will be able to tell you if luspatercept is available and whether it is suitable for you.
Luspatercept is now being investigated in clinical trials to see if it can help with non-transfusion-dependent BT and to see if it can be used in children.
Information based on Fast Facts for Patients: Beta Thalassemia (Karger, 2023).
This is the fourth part of our series about the condition based on our patient booklet “Fast Facts for Patients: Beta Thalassemia”. This article lists complications associated with beta thalassemia (BT) and how they can be treated.
Complications
There are a number of complications that you may develop if you have BT. Some of these are the result of the disease itself, particularly if you don’t have the treatment you need. Others are the result of a combination of the disease and its treatment.
Bone Changes
Children with BT major (and some with BT intermedia) who don’t receive treatment may have bone deformities that develop slowly over time. The skull expands and heavy brows develop. Your doctor may call this ‘bossing’. The cheekbones get bigger, which alters the shape of the face, nose and eyes. It also affects the placement of the teeth.
‘Bossing’ does not mean that the bones become harder – in fact they are thinner and more fragile. Your doctor may call this osteopenia or osteoporosis. This increases the risk of fractures, mainly in the spine, ribs, pelvis and long bones.
Osteopenia means that your bones have started to become thinner and more fragile. Osteoporosis means you have more severe bone thinning.
Why Do Bone Deformities Occur?
Normally, blood cells are made inside the bones by a tissue called bone marrow. In BT there are fewer circulating red blood cells and less Hb than normal. To try to make up for this, the bone marrow becomes overactive and produces more and more red blood cells. But as these are abnormal, they die early and don’t help to correct the anemia.
As the bone marrow continues to try to correct the anemia, it expands and this causes the bones to become bigger. It is this that causes the typical bone changes of BT. The more severe the form of BT, the more noticeable these changes will be. Treatment is with red blood cell transfusions.
An Enlarged Spleen
Some people with BT major may also develop an enlarged liver (hepatomegaly) and spleen (splenomegaly), leading to abdominal swelling. This happens because the spleen removes faulty red blood cells and also because the liver and spleen become alternative sites for red blood cell production.
A very enlarged spleen can cause abdominal discomfort and make anemia worse. So, it may have to be removed. Splenomegaly is more common and severe if you have non-transfusion-dependent BT. If you are having transfusions you will be receiving healthy normal red blood cells from donors and your spleen won’t have to work so hard.
If you have BT trait, you may also have a slightly enlarged spleen, but not enough to cause symptoms.
Gallstones
Gallstones can develop because of high levels of bilirubin in the liver caused by the chronic hemolysis. Hemolysis is the destruction of red blood cells.
If you have gallstones, you may feel bloated and sick (nauseated) and have abdominal pain. You may need surgery to have your gallbladder and the stones removed.
Blood Clots
There is an increased risk of blood clots (thrombosis) as you get older, particularly if you have non-transfusion-dependent BT. The risk is higher if you’ve had your spleen removed.
Benign Masses
Sometimes in BT, if the bone marrow isn’t able to make enough blood cells, they can be made outside the bone marrow, in the liver and spleen. This can cause the liver and spleen to get bigger. But it can also cause small slow-growing lumps of tissue to develop, usually in the chest near the spine. These lumps (masses) are harmless but they can sometimes press on spinal nerves and cause problems. Although they are completely benign (not cancerous), doctors need to distinguish them from tumors on scans and X-rays and this can be difficult. Blood transfusions can prevent these from developing.
When red blood cells are made in tissues other than the bone marrow, this is called extramedullary erythropoiesis. Common sites of extramedullary erythropoiesis include organs such as the liver and spleen, as well as lymphatic tissue, especially all along the spine.
Leg Ulcers
Untreated BT intermedia can lead to problems with wound healing. Even minor wounds on the legs, particularly the ankles, don’t heal and may get worse and become infected. These are treated with dressings to help them heal and antibiotics if infected.
Iron-Related Complications: Iron Overload
Normally, when ageing red blood cells are broken down in the body, the iron that’s released is recycled into new cells. When a person has regular blood transfusions, iron overload can also happen as donor red cells contain iron. Iron overload is when there is too much iron in your body. As the body can’t get rid of all the extra iron, it builds up and can cause damage.
Iron overload can also develop in people who don’t have regular transfusions (non-transfusion-dependent BT), but it develops more slowly. The buildup occurs because the overactive bone marrow sends signals to the gut to absorb much more iron from the diet. This happens because the body tries to correct the anemia by making more red blood cells and for this it needs iron.
Iron buildup can damage the liver, causing fibrosis. Fibrosis is scar tissue that replaces damaged liver tissue. If not controlled, fibrosis can develop into cirrhosis and liver failure.
Iron overload can also cause heart damage, leading to abnormal heart rhythms (arrhythmia) and eventually heart failure. Excess iron can also damage your bones and joints, increasing the risk of weakened bones (osteoporosis).
Hormone levels can be affected by iron overload too. Your thyroid hormone levels may be low, which can cause fatigue, weight gain and constipation.
You may be at a higher risk for diabetes. Iron affects the production of insulin in the pancreas, which controls blood sugar levels.
You may also have low levels of sex hormones. Puberty is often later than usual in children with BT. The low hormone levels may cause reduced fertility.
To help prevent all the problems caused by iron toxicity, your iron levels may need to be controlled with treatment called chelation therapy. Iron levels can be kept low and safe by the daily use of medicines called iron chelators.
Pregnancy-Related Complications
There are no particular complications from carrying a baby with BT. But if you have BT, pregnancy can put an extra strain on your body and make your symptoms worse. You may also have difficulty becoming pregnant, as iron overload can affect fertility (because of the effect on hormone levels).
You will need extra tests to check your heart, liver and bone health. If you are on chelation therapy, you will have to stop for the first half of the pregnancy because the medicines could be toxic for the baby.
Your Hb levels will be closely monitored and you may need transfusions more often, particularly as the pregnancy progresses.
Treatment for Complications
Some people need surgery for complications of BT, such as an enlarged spleen or gallstones.
Enlarged Spleen
A very enlarged spleen can cause abdominal discomfort and make anemia worse, so it may have to be removed. In BT, removing the spleen improves anemia and reduces the need for such frequent blood transfusions in some people.
Because BT is now much better controlled with transfusions, fewer people develop a very enlarged spleen and so splenectomy (surgery to remove the spleen) isn’t done as often. However, people with non-transfusion dependent thalassemia may also need a splenectomy, as their thalassemia isn’t managed with transfusions.
Splenectomy is a major operation and will require a stay in hospital and you will need time to recover. You may have open surgery (one larger incision) or laparoscopic surgery (several small incisions). Laparoscopic surgery is sometimes called keyhole surgery or bandaid surgery. With keyhole surgery, your hospital stay is generally shorter and recovery from surgery is faster.
There can be other problems after you’ve had your spleen removed.
In BT, removing the spleen increases your risk of developing blood clots (thrombosis). This risk is lifelong and is the main reason why the benefits of surgery must be carefully weighed against the risks.
The spleen is part of your body’s defense against infection so you are more at risk without it. To give you added protection, you will need some vaccinations, ideally before your surgery. If your child has their spleen removed, your doctor may also want them to take antibiotics daily for a couple of years after surgery to prevent infection. Or you may have an antibiotic prescription at home, so you can start taking them quickly if needed.
Gallstones
Stones in your gallbladder can be very painful and make you feel very unwell.
The treatment is usually surgery to remove your gallbladder. You may have open surgery or keyhole surgery.
Keyhole surgery usually means a shorter stay in hospital and a quicker recovery as there is no large incision.
Blood Clots
People with BT may develop blood clots. The risk is higher in certain circumstances, such as before planned surgery, during pregnancy or after having your spleen removed. Your doctor may suggest you take medicines to reduce the risk of your blood clotting. You will have to have these if you’ve had your spleen removed. These medicines are called anticoagulants and include low-dose aspirin and heparin-like medicines.
Information based on Fast Facts for Patients: Beta Thalassemia (Karger, 2023).
This is the third part of our series about the condition based on our patient booklet “Fast Facts for Patients: Beta Thalassemia”. This article focuses on the screening for and diagnosis of beta thalassemia (BT).
Newborn Screening
In some parts of the world all newborn babies are screened for several genetic conditions. A nurse will prick the baby’s heel with a fine needle and squeeze out a drop of blood, which is then used for the testing. The heel prick test is not a reliable test for all types of thalassemia but it can pick up BT major.
Diagnostic Testing
Children with the most severe forms of BT can develop symptoms from 3 months of age.
If your child has symptoms that suggest they may have BT, your doctor will request blood tests. These tests look for iron deficiency to rule out the commonest cause of anemia.
The blood tests will also analyze the Hb level, the shape and size of the red blood cells and look for changes in the structure of the Hb molecule. Carriers of a BT gene change and people with BT have red blood cells that are smaller than normal. This is a particular feature of BT called microcytosis. The specific test for BT is usually HPLC – high performance liquid chromatography – or sometimes electrophoresis.
Microcytosis is the term used to describe red blood cells that are unusually small.
DNA Tests
More than 400 gene changes are associated with BT. DNA (genetic) tests need to be done on a blood sample to identify the specific ones you have. The sample may need to be sent to a specialized laboratory for these tests.
Pregnancy Screening
Depending on your ethnic background or family history, your doctor may suggest you have blood tests for thalassemia if you are planning to start a family.
Ideally, tests for BT should be carried out before the start of pregnancy. But in practice, most women usually have blood tests when they first go to their doctor after becoming pregnant. If your blood test shows anemia and/or small red blood cells, your doctor is likely to suggest further testing for BT. If you are found to have BT trait (one changed gene), the baby’s father will also need to be tested, to see if there is a risk your baby could be born with BT.
Genetic Counseling and Pregnancy
If your doctor suspects you have a BT gene change, they may suggest genetic counseling for you and your partner. The counselor will help you understand why you are considered a ‘couple at risk’ for BT and will explain what your test results mean.
If the blood test results show there is a risk that your child could be born with BT, the counselor will continue to provide support. You will also be able to discuss your options when planning a pregnancy. Some couples opt to have in vitro fertilization (IVF or a test tube baby) so that genetic testing can be carried out before the fertilized egg is implanted. This makes sure that the baby doesn’t have BT.
If you are already pregnant and there is a risk that the baby has BT, it’s possible for the baby to be tested while still in the womb. This is usually done in one of two ways:
- taking a small sample of the placenta (chorionic villus sampling)
- testing the fluid surrounding the baby (amniocentesis).
Which test you have depends on how far through the pregnancy you are. Both tests carry a small risk of miscarriage, so your doctor will only suggest testing if absolutely necessary.
There are some non-invasive tests that are under investigation, such as testing fetal DNA found in the mother’s bloodstream. These may be useful in future, but they are currently not accurate enough to use for thalassemia and give high levels of wrong results.
If tests suggest that a baby may be born with severe BT, your counselor may guide you through the difficult decision of whether to continue with the pregnancy. There is no single answer that suits every couple. The decision depends on lots of different factors, including cultural, social, spiritual and religious beliefs. Being fully informed about the disease will help you make a decision.
Information based on Fast Facts for Patients: Beta Thalassemia (Karger, 2023).
This is the second part of our series about the condition based on our patient booklet “Fast Facts for Patients: Beta Thalassemia”. This article explains the different types of beta thalassemia (BT), this is: trait, intermedia, and major.
Symptoms of BT vary depending on which kind of gene change you have inherited. Because it’s complex and to make things simpler, doctors generally put people with BT into two groups, regardless of the gene changes they have – people who depend on regular blood transfusions and those who don’t. So, your BT may be described as transfusion dependent or non-transfusion dependent. People who need regular blood transfusions have more severe anemia (fewer healthy red blood cells).
You may also hear the terms beta thalassemia intermedia and beta thalassemia major.
- BT intermedia describes less severe disease that does not need regular blood transfusions (although you may need more transfusions as you get older). It generally occurs when one or both gene changes are less severe.
- BT major describes severe disease since early childhood requiring lifelong regular blood transfusions. It generally results from a combination of two severe gene changes.
Other Types of Inherited Blood Disorders
Sometimes people inherit a combination of a BT gene change and a change in a gene that causes another condition that affects Hb production. For example, some people have one BT gene change and the gene change that causes sickle cell disease: this combination causes a disease called sickle BT. Another condition is alpha gene triplication.
Beta Thalassemia Trait
If you have only one changed HBB gene, you are a healthy carrier of BT but do not have, and will never develop, the disease. This is called beta thalassemia trait or beta thalassemia minor.
Normally BT trait doesn’t cause symptoms so you may not know you have a BT gene change. A routine blood test may raise suspicions that you are a carrier but cannot prove this – you need to have specific DNA (genetic) tests carried out on a blood sample to find any thalassemia changes.
BT carriers are healthy people who don’t have thalassemia. You may have mild anemia, but this doesn’t generally need treatment. You may have a pale complexion.
Under a microscope, your red blood cells will look small (microcytosis). A doctor who doesn’t know your medical history may assume this is due to low iron, but it’s not and you don’t need iron supplements. In fact, you shouldn’t take iron supplements unless a specific blood test shows that you are definitely deficient.
What Is the Risk If I Have Children?
If you carry a mutated HBB gene you have a 1 in 2 risk (50%) of passing it on to a child for each pregnancy that you conceive.
If your partner also has BT trait, there is a 1 in 4 chance (25%) of a baby having BT and a 1 in 4 chance (25%) of them not inheriting the gene mutation at all.
Your doctor may suggest you have genetic counseling if you have BT trait.
What Can I Do to Help Myself?
You may feel tired if you have mild anemia, particularly if your body is under any extra strain, such as during pregnancy, or if you have an infection or have had surgery.
You can help yourself to stay healthy by
- eating healthily
- exercising regularly
- not smoking or drinking too much alcohol.
Should I Tell Other People?
When and how should you tell people that you are a thalassemia carrier? The simple answer is: whenever you are ready. Mostly, you don’t have to tell people if you don’t want to. But you particularly need to be open with your partner if you are thinking of starting a family in the future. They will need to be tested too.
Talking about a genetic problem can be difficult. People sometimes feel it’s their fault. But you have no control over the genes you inherit. You can use this booklet to help others understand more about BT.
Beta Thalassemia Intermedia
Symptoms of BT intermedia can appear at any point. You may not need transfusions as it depends on the severity of your anemia and whether you need to prevent or control long-term complications. Your doctor will advise you about this.
Signs and Symptoms
You may:
- look pale
- lack energy when active or exercising
- not grow as much as expected
- not gain as much weight as expected
- have abdominal swelling, caused by the spleen getting bigger.
These may be the only symptoms if the condition is diagnosed early.
The spleen enlarges because one of its functions is to recycle and remove old and faulty red blood cells.
Symptoms can get worse when the body is under stress, because the need for oxygen is higher. Stress includes having an infection, recovering from surgery and during pregnancy.
Beta Thalassemia Major
BT major is a lifelong condition, with symptoms usually appearing during the first 2 years of life.
Signs and Symptoms
BT major causes severe signs and symptoms because the body is not able to make normal Hb. It is a transfusion-dependent condition.
Babies with BT major become thin and pale during their first year because of severe anemia. They also show early signs of bone changes.
Why Is Treatment Important?
It’s important for all children and adults with BT major to have treatment to control the disease and try to prevent complications as far as possible. If you don’t, you are more likely to develop further problems as your body tries to cope with the faulty red blood cells.
Information based on Fast Facts for Patients: Beta Thalassemia (Karger, 2023).
This is the first part of our series about the condition based on our patient booklet “Fast Facts for Patients: Beta Thalassemia”. This article shows what beta thalassemia (BT) is and what causes it.
First, the Facts
- Beta thalassemia (BT) is a blood condition you’re born with. It affects your red blood cells.
- BT is a disease caused by changes (mutations) in genes that are passed on from parent to child. You have BT when you inherit a gene change from both of your parents.
- There are two types of BT disease – BT major and BT intermedia. A person can also be a healthy carrier of BT without having the disease. This is called BT trait (or BT minor).
- Treatment depends on the type of BT disease you have. People with BT major will require regular blood transfusions throughout their life.
- New treatments for BT have recently been approved or are being tested in clinical trials around the world, with promising results.
What Is Beta Thalassemia?
Thalassemia is a condition you are born with. It affects red blood cells. There are two main types: alpha thalassemia and beta thalassemia (BT). This booklet is about BT.
In BT, the body doesn’t make enough normal hemoglobin (Hb). Hb is the protein in red blood cells that enables them to carry oxygen around the body. There are also too few healthy red blood cells.
This is called anemia. Anemia can be mild or serious. Serious anemia can damage organs and can be fatal.
Types of BT
There are different types of BT. How severe your condition is and how bad your symptoms are depends on the type you have. You may have no symptoms, or you may need lifelong treatment.
Why Isn’t the Hemoglobin Made Properly?
Each molecule of normal adult Hb is made up of four protein chains – two alpha chains and two beta chains. If you have BT, your body is not producing enough of the beta chain. That means you cannot make enough normal Hb, so less oxygen can be carried around your body.
What Causes Beta Thalassemia?
BT is a genetic condition. This means it is caused by a change (also called a mutation) in a gene. There can be different types of change – some cause the beta chains of Hb to be missing completely, while others cause a decrease in beta chain production.
What Are Genes?
Your genes carry instructions for the growth, development and function of your entire body.
Genes are found on chromosomes. Every cell in the human body has 23 pairs of chromosomes – so 46 chromosomes in total. Every chromosome has anywhere from 55 to 20 000 genes.
Genes are in pairs too – you inherit one copy from your mother and one copy from your father. A pair of genes is carried on a pair of chromosomes (one gene on each chromosome).
Each pair of genes carries the code to make a single protein.
The gene that carries the instructions for making the beta chain protein of Hb is called HBB.
Who Gets BT?
BT is more common in some parts of the world where malaria is, or has been, a problem (for example, the Mediterranean, the Middle East, North Africa, India and Southeast Asia) and in people with ancestry originating from these areas. This is because the gene changes that cause BT also give some protection against malaria.
Over time, the proportion of people in the population with a BT gene change has increased and, as people migrate around the world, BT has become more common in other regions too.
Inheriting Beta Thalassemia
BT is nearly always a recessive genetic condition. In recessive conditions, both genes in a pair have to be affected to produce disease. This means you have to inherit a mutated gene from both of your parents to have the condition. So, either your parents have BT themselves, or, more commonly, they are ‘carriers’ of a mutated HBB gene.
Carriers have one mutated HBB gene and one healthy HBB gene. Because they have one healthy gene, they can still make enough healthy Hb beta chain protein. They will never develop BT, but they can pass on the mutated gene to their children.
Being a carrier of a single mutated HBB gene is called beta thalassemia trait or beta thalassemia minor.
How Do Gene Changes Cause Beta Thalassemia?
There are many different changes to the HBB gene that can cause BT. How severely you are affected will depend on the type of gene change that you have. There are two main types of changes:
- Those that result in less beta chain protein than normal being made. Doctors write this as β+.
- Those that result in no beta chain protein being made. Doctors write this as β0.
Because there are two HBB genes, a person can have a combination of these types of change. You may have β+/β+, β+/β0 or β0/β0.
If only one gene of the pair is affected (BT trait), you may have β+/β or β0/β.
There is another possible gene change, called HbE. This results in the production of an abnormal type of Hb known as hemoglobin E. So, you can also have the gene combinations β+/E+ or β0/E+.
Information based on Fast Facts for Patients: Beta Thalassemia (Karger, 2023).
This is the ninth and last part of our series about the condition based on our patient booklet “Fast Facts for Patients: Alpha Thalassemia”. This article provides information on living with alpha thalassemia (AT).
Some people with AT already know that it runs in their family. For others, it’s a complete shock when they are diagnosed with AT because of anemia symptoms or when a baby is diagnosed shortly after birth. Genetic counseling can help you to understand your condition and its implications, including the risk to any future children you may have.
You are likely to have a lot of questions. It’s important to find out as much as you can about AT and about your own situation.
AT is complicated and it’s easy to get confused. It may help to write down a list of the things you need to know or questions you want to ask and take it to your doctor’s appointment. It may also help to take someone with you, so you can compare notes afterwards.
Should I Tell Other People?
When should you tell people that you are a thalassemia carrier or have AT trait? The simple answer is: whenever you are ready. Mostly, you don’t have to tell people if you don’t want to. But you particularly need to be open with your partner if you are thinking of starting a family in the future. They will need to be tested too.
Talking about a genetic problem can be difficult. People sometimes feel it’s their fault. But you have no control over the genes you inherit. You can use this booklet to help others understand more about AT.
Important: Living a healthy life is important for everyone. When you have thalassemia, healthy choices are particularly important.
The best way to avoid complications is to stick to any treatment schedules and go to all your check-up appointments.
Important: Contact your doctor promptly if you have any signs of infection or other illness, and make sure you keep your vaccinations up to date – especially if you’ve had your spleen removed.
Your Diet
It’s important to look after your general health. Make sure you eat well.
People with thalassemia often have low levels of some vitamins and minerals, such as zinc. This is partly because of the anemia, and partly because of high iron levels and the treatment used to remove iron. Your doctor may give you supplements.
Some doctors suggest avoiding foods that contain iron, but others think that this has little effect in preventing iron overload. It’s best to discuss your diet with your own AT healthcare team.
Keep Fit for Healthy Bones
Regular physical exercise has many benefits. It can improve your mood and help strengthen your bones. Alcohol and smoking are best avoided.
Ask for Help If You Need to
Do ask questions and tell your healthcare team about anything that’s concerning you. They know how complex AT is and won’t mind, even if you ask the same questions more than once.
Questions for Your Doctor
- What type of AT do I/does my child have?
- How many gene changes are there?
- Are they deletional or non-deletional gene changes?
- What are the implications of the gene changes I have?
- What impact will AT have on me/my child?
- Will I/they need regular treatment?
- What are the likely side effects of treatment?
- What complications could there be and how likely are they?
- What is the likelihood of me having another child with AT?
- Is there anything that can be done to reduce the risk of having another child with AT?
- Will my child with AT be able to have children and what do they need to know beforehand?
Please check out the other posts of our series here:
Information based on Fast Facts for Patients: Alpha Thalassemia (Karger, 2023).
This is the eighth part of our series about the condition based on our patient booklet “Fast Facts for Patients: Alpha Thalassemia”. This article shows what clinical trials are and which new treatments are on the horizon.
Clinical Trials
If you are interested in new treatments, you may want to ask your doctor about clinical trials. All new medical treatments have to be tested in clinical trials. A new treatment must go through several phases of testing before it can be proven to work better than existing treatment and be adopted into routine care. A potential treatment will only move on to the next phase of research if it is safe and shows promise.
New Treatments for Alpha Thalassemia
Slowing the Breakdown of Red Blood Cells
There has been some research looking into treating anemia in people with AT with medication to reduce the destruction of red blood cells.
Mitapivat is a new treatment that is being tested in people with AT or beta thalassemia. It’s a tablet that you take twice a day. It’s already used to treat another genetic condition that causes anemia, called pyruvate kinase deficiency.
This treatment helps to activate an enzyme that is needed for red blood cells to function properly. Early trial results show that it may be able to reduce anemia in people with AT who don’t need regular blood transfusions. Side effects found so far include difficulty sleeping, headache and dizziness.
Mitapivat is being tested in a Phase III trial for people with AT who do and do not require regular transfusions.
Stem Cell Transplant
The only way to potentially cure AT is with a stem cell transplant from a donor. Stem cell transplant is currently only suitable for AT major, as the treatment itself has many side effects, some of which can be life-threatening.
Stem cells are cells in the bone marrow that can develop into all the different types of blood cell in the body, including red blood cells.
When you have a transplant, the stem cells in your bone marrow are destroyed and replaced with healthy cells from the donor. The donor must be someone whose blood cells closely match yours, and this is usually a close family member.
The aim is for the donor stem cells to start to grow inside your bones and provide new blood stem cells to replace yours. This process is called ‘engraftment’. The new stem cells will produce all the different types of blood cells, including healthy red blood cells.
Until the new stem cells have started to work, you have a very high risk of infection. So, you need to be nursed in isolation for some time after having your stem cell infusion.
Please check out the other posts of our series here:
Information based on Fast Facts for Patients: Alpha Thalassemia (Karger, 2023).
This is the seventh part of our series about the condition based on our patient booklet “Fast Facts for Patients: Alpha Thalassemia”. This article lists the symptoms and treatment of alpha thalassemia (AT).
How Will AT Affect Me or My Child?
Symptoms of AT vary depending on which type of AT you have. Some people have no symptoms while others have severe symptoms that need lifelong treatment.
Complications are health problems caused by the disease (AT) or by the treatment. Complications also vary from mild to severe.
Silent carrier. As a silent carrier, you won’t have any symptoms of AT and will have no health problems related to AT.
AT trait. With AT trait, symptoms vary from none to mild anemia. This can cause fatigue, particularly after exercise, and pale skin and you may feel weak.
HbH AT. Symptoms and complications are more severe in people with HbH AT. They include anemia, enlarged liver and spleen, gallstones, abnormal bone development, blood clots and iron overload (see below).
AT major. Children and adults with AT major will need regular treatment to prevent severe anemia. They are also at risk of all the complications that can happen with HbH AT.
Anemia
People with more severe HbH AT and AT major will have more severe anemia, which causes increased fatigue, difficulty breathing, weakness and dizziness.
Anemia can sometimes get worse with age or when the body is under stress: for example, if you have an infection or during pregnancy.
Babies born with HbH AT may have anemia but don’t usually need regular treatment.
Children and adults with AT major will need regular treatment for anemia.
Treatment
The main treatment for anemia is blood transfusions. Blood transfusions provide healthy red blood cells.
How Often Will I Need Blood Transfusions?
How often people with HbH AT (three gene changes) need blood transfusions varies. It depends on how severe their anemia is and it also depends on their age. Some people with HbH AT need regular transfusions by the time they reach their teens or 20s.
People with AT major (four gene changes) will need regular transfusions throughout their lives. Transfusions can happen every couple of weeks.
You receive blood through a small plastic tube inserted into one of the blood vessels in your arm. The procedure usually happens in a hospital or a special clinic for blood diseases. Babies, children and adults can have transfusions. The procedure will take a few hours each time.
Doctors also sometimes prescribe folic acid tablets to help with anemia. Folic acid is a kind of vitamin which helps to produce red blood cells.
Enlarged Liver and Spleen
HbH AT and AT major can cause the liver and spleen to get bigger than normal, and your abdomen may feel uncomfortable. You may have pain too. It happens because the spleen has to work hard to get rid of the faulty red blood cells and the liver has to work hard to process the resulting waste products.
Treatment
If an enlarged spleen is causing discomfort and pain, you may need surgery to remove it. The removal of a spleen is called splenectomy. Blood transfusions can also help to shrink an enlarged spleen. People who have had a splenectomy have a higher risk of infections. Your hematologist and general surgeon will discuss the risks and benefits with you.
Gallstones
These can develop because of high levels of bilirubin (a waste product from the processing of red blood cells). Some people with gallstones have no symptoms, but others may feel bloated and sick (nauseated) and have abdomen pain.
Treatment
The treatment is usually laparoscopic surgery (sometimes called keyhole or bandaid surgery) to remove your gallbladder. Keyhole surgery usually means that you recover more quickly because there is no major incision.
Abnormal Bone Development
Normally, blood cells are made inside the bones by a tissue called bone marrow. In AT there are fewer circulating red blood cells and less Hb than normal. To try to make up for this, the bone marrow becomes overactive and produces more and more red blood cells. But as these are abnormal, they die early and don’t help to correct the anemia. As the bone marrow continues to try to correct the anemia, it expands and this may cause the bones to become bigger, particularly in the face, causing a ‘heavy’ forehead and overgrowth of the brows and jaw. Your doctor may call this bossing.
With untreated AT, limbs can also be shorter than usual because the long bones stop growing early. Bones may also become weakened and break more easily. Your doctor may call this osteoporosis or osteopenia.
Treatment
If you or your child have HbH AT or AT major, you will have regular health checks so that any abnormal bone development is found early. Regular blood transfusions and the treatment for iron overload usually helps prevent bone problems.
Blood Clots
People with AT have a slightly increased risk of blood clots. The risk is higher in people who have had their spleen removed and the risk increases with age. Blood clots are more common in women.
Treatment
Treatment for blood clots varies but may include aspirin or low-dose blood thinners. These are called anticoagulants.
Leg Ulcers
HbH AT can cause problems with wound healing. Even minor wounds on the legs, particularly the ankles, don’t heal and may become infected and need antibiotics.
Iron Overload
Iron overload is a common complication of AT major and HbH AT.
Normally, when aging red blood cells are broken down in the body, the iron that’s released is recycled into new cells. When a person has regular blood transfusions, iron overload can happen as donor blood also contains iron. Iron overload is when there is too much iron in your body. It can also develop in people with HbH AT who do not have regular transfusions but it happens more slowly. The buildup occurs because the overactive bone marrow sends signals to the gut to absorb much more iron from the diet. This happens because the body tries to correct the anemia by making more red blood cells and for this it needs iron.
Why Is Iron Overload a Problem?
Too much iron is toxic to the body as the body is not able to remove it. The excess iron increases over time and can damage your organs.
Iron buildup can damage the liver. The damaged liver tissue is replaced by fibrous tissue, also called scar tissue. This process is called fibrosis. A research study found that around 1 in 5 people (20%) with HbH AT have liver tissue that has been replaced with fibrous tissue (fibrosis). If fibrosis gets worse, it can develop into liver cirrhosis and liver failure.
Iron overload can cause heart damage, leading to abnormal heart rhythms (arrhythmia) and eventually heart failure.
It can also damage your bones and joints. People with AT major and HbH AT are prone to weakened bones (osteoporosis). This is partly due to the thalassemia, but iron overload also contributes because iron can collect in the bones and cause damage.
Hormone levels can be affected by iron overload. Your thyroid hormone levels may be low, leading to fatigue, weight gain and constipation. You may also be more at risk of developing diabetes, because iron affects the production of insulin in the pancreas, which controls your blood sugar levels.
If you are receiving blood transfusions, you may have low levels of sex hormones. In children with AT, this can mean that puberty is later than usual. This is less common these days, because many children have well-managed anemia and iron levels after their AT diagnosis.
Treatment
To help prevent all the problems caused by iron toxicity, your iron levels may need to be controlled by a treatment called chelation therapy. There are three types of chelation therapy. You may have it through continuous intravenous infusion (directly into a vein), through your skin (subcutaneously) or by mouth (orally). Your doctor will discuss the choice of chelation therapy with you and any possible side effects.
Your doctor will monitor your iron level with blood tests. If it seems high, you may have an MRI (magnetic resonance imaging) scan to measure the iron concentration in your liver and/or your heart. This will show whether you need chelation therapy.
Important: If your doctor says you need chelation therapy, it is very important that you follow their instructions. Iron overload can be fatal.
Your Healthcare Team
AT is a complex health condition and needs specialist care. Your treatment should be managed by a specialist center for blood disorders and overseen by a consultant hematologist (a doctor that specializes in treating blood disorders and diseases).
Specialist centers will often have a thalassemia clinical nurse specialist, who you can contact if you have any questions when you’re at home.
Please check out the other posts of our series here:
Information based on Fast Facts for Patients: Alpha Thalassemia (Karger, 2023).
This is the sixth part of our series about the condition based on our patient booklet “Fast Facts for Patients: Alpha Thalassemia”. This article focuses on the aspects of screening and diagnosis in alpha thalassemia (AT).
Newborn Screening
In some parts of the world, all newborn babies have a blood test for thalassemia. A nurse pricks the baby’s heel with a fine needle and squeezes out a drop of blood. This is used to test for other genetic conditions as well.
It is unlikely that the test will find one or two gene changes but it is likely to find HbH AT (three gene changes).
Diagnostic Testing in Children and Adults
A doctor may suggest testing for thalassemia because you (or your child) show some of the symptoms of AT or if a routine blood test shows that you or your child have mild microcytic anemia.
Often, doctors test for iron deficiency first because it’s a common cause of microcytic anemia. They will do other tests to look for HbH AT and AT trait.
These tests can’t show how many AT genes are affected though.
To identify the exact genetic changes, you’ll need to have DNA tests done on a blood sample.
Genetic Counseling
Before having screening tests for thalassemia, you may be offered genetic counseling. This is to make sure you understand any tests you might have and what the results may mean.
Usually, the partners of people with two gene changes on the same chromosome or three gene changes (HbH AT) will also need to have a DNA test.
The counselor will continue to provide support after testing if results show that there is a risk that your children could have three or four gene changes. You will be able to discuss the options when planning a pregnancy.
Some couples decide to have in vitro fertilization (also known as IVF or a ‘test-tube baby’) so that genetic testing can be carried out before the fertilized egg is implanted in the womb. Depending on the gene changes that the parents have, genetic testing can make sure that the baby doesn’t have AT major or doesn’t have any AT gene changes at all.
Pregnancy Screening
If you’re already pregnant, your doctor will want to do genetic testing early in the pregnancy in case your baby needs treatment before birth. This helps to prevent premature birth and avoid serious complications for the mother.
If there is a risk that the baby could have AT major, the doctor will suggest testing the baby while still in the womb.
There are different ways to do the test:
- taking a sample of blood from the umbilical cord (cordocentesis)
- testing the fluid surrounding the baby (amniocentesis)
- taking a sample of the placenta (chorionic villus sampling).
Which test you have depends on how far through the pregnancy you are. All the tests carry a small risk of miscarriage, so your doctor will only suggest testing if it is absolutely necessary.
Ultrasound analysis may be used and some non-invasive tests are currently under investigation, such as testing fetal DNA found in the mother’s bloodstream. These may be useful in future, but they are currently not accurate enough to use for thalassemia and give high levels of wrong results.
Invasive sampling means a sample of tissue or fluid is taken from inside the body. This is done via a cut in the skin or through a body opening.
Babies and AT Major
Birth defects are more likely in babies born with AT major, even if they have blood transfusions in the womb. The most common birth defects are minor abnormalities of the genitals in boys. For example, the opening of the urethra (the tube you pee through) can be on the underside of the penis. This is called hypospadias and can be fixed with surgery.
Around 1 in 6 babies (about 17%) have a limb abnormality. These vary in how severe they are. Examples include having hands of different sizes or part of a foot that hasn’t fully developed.
A baby with AT major who does not receive an intrauterine transfusion before he is born will be likely to die in the womb.
Depending on the results of the tests, your counselor may take you through the difficult decision of whether to continue with the pregnancy. There is no single answer that suits every couple. The decision depends on many factors, including cultural, social, spiritual and religious beliefs.
Pregnancy
A pregnant woman with AT needs special care during her pregnancy. Anemia can become more severe. A condition called pre-eclampsia is also more common, which can be fatal if not detected. Signs of pre-eclampsia include rising blood pressure and protein in the urine (signs of damage to the liver or kidneys).
The mother will have regular tests for these during her pregnancy and will often take medication to lower blood pressure.
Please check out the other posts of our series here:
Information based on Fast Facts for Patients: Alpha Thalassemia (Karger, 2023).
This is the fifth part of our series about the condition based on our patient booklet “Fast Facts for Patients: Alpha Thalassemia”. This article explains four gene changes in alpha thalassemia (AT).
If you have four gene changes, you have no genes that make alpha chains properly. This is called AT major or Hb Barts disease. This is the most serious form of AT.
What Does This Mean?
When a baby starts to develop in the womb, the first type of Hb its body makes is called embryonic Hb, which doesn’t include any alpha chains. By 16 weeks, the baby begins to make another type of Hb called fetal Hb, which needs alpha chains.
A baby with four gene changes can’t make alpha chains, so fetal Hb cannot develop. Instead, a type of Hb called Hb Barts is made. The baby will develop severe anemia and will die in the womb without treatment. Doctors call this ‘hydrops fetalis’ (or just ‘hydrops’ for short).
It may be possible for the baby to have red blood cell transfusions while still inside the womb (this is called intrauterine transfusion), so the chance of the baby living until birth is greatly increased. However, there is still a high risk of premature birth.
Your health will also be closely monitored throughout your pregnancy. Your medical team will do everything they can to lower the risk of complications for both you and the baby.
What Is the Risk If I Have Children?
If one parent has four gene changes and their partner has two gene changes on the same chromosome, for each pregnancy there is a:
- 1 in 2 chance (50%) the baby will have AT major (four gene changes)
- 1 in 2 chance (50%) the baby will have AT trait (two AT genes on the same chromosome).
If one parent has four gene changes and their partner has two gene changes on different chromosomes, every child will have HbH AT (three gene changes).
If one parent has four gene changes and their partner has HbH AT (three gene changes), for each pregnancy there is a:
- 1 in 2 chance (50%) the baby will have AT major (four gene changes)
- 1 in 2 chance (50%) the baby will have HbH AT (three gene changes).
Please check out the other posts of our series here:
Information based on Fast Facts for Patients: Alpha Thalassemia (Karger, 2023).
This is the fourth part of our series about the condition based on our patient booklet “Fast Facts for Patients: Alpha Thalassemia”. This article focuses on three gene changes in alpha thalassemia.
If you have three gene changes, you have Hemoglobin H AT (HbH AT).
What Does This Mean?
The symptoms and complications you experience will depend on the type of gene change you have.
People with non-deletional HbH tend to have more severe disease than people with missing AT genes (deletional HbH).
You may have only mild anemia or it may be severe enough for you to need regular blood transfusions from a young age.
What Is the Risk If I Have Children?
If one parent has three gene changes but the other parent has no changes, for each pregnancy there is a:
- 1 in 2 chance (50%) the baby will be a carrier (one gene change)
- 1 in 2 chance (50%) the baby will have AT trait (two gene changes on the same chromosome).
If one parent has three gene changes and the other has one gene change, for each pregnancy there is a:
- 1 in 4 chance (25%) the baby will be a carrier (one gene change)
- 1 in 2 chance (50%) the baby will have AT trait (two gene changes)
- 1 in 4 chance (25%) the baby will have HbH AT (three gene changes).
If one parent has three gene changes and the other has two gene changes on the same chromosome, for each pregnancy there is a:
- 1 in 4 chance (25%) the baby will be a carrier (one gene change)
- 1 in 4 chance (25%) the baby will have AT trait (two gene changes on the same chromosome)
- 1 in 4 chance (25%) the baby will have HbH AT (three gene changes)
- 1 in 4 chance (25%) the baby will have AT major (four gene changes).
If one parent has three gene changes and the other has two gene changes, one on each chromosome, for each pregnancy there is a:
- 1 in 2 chance (50%) the baby will have AT trait (two gene changes changes, one on each chromosome)
- 1 in 2 chance (50%) the baby will have HbH AT (three gene changes).
If both parents have three gene changes, for each pregnancy there is a:
- 1 in 4 chance (25%) the baby will have AT trait (two gene changes on the same chromosome)
- 1 in 2 chance (50%) the baby will have HbH AT (three gene changes)
- 1 in 4 chance (25%) the baby will have AT major (four gene changes).
Please check out the other posts of our series here:
Information based on Fast Facts for Patients: Alpha Thalassemia (Karger, 2023).
This is the third part of our series about the condition based on our patient booklet “Fast Facts for Patients: Alpha Thalassemia”. This article provides information on two gene changes in alpha thalassemia (AT).
If you have two gene changes, you are said to have AT trait, which is also called AT minor.
What Does This Mean?
Most people with two gene changes don’t have any serious health problems related to AT, apart from mild anemia (a shortage of healthy red blood cells). Anemia can cause fatigue, particularly after exercise).
Under a microscope, your red blood cells will look smaller than usual. Doctors call small red blood cells microcytosis. The cells look like this because of a lack of Hb.
Important: If you’re anemic, make sure your doctor knows that you have AT trait (or that there is thalassemia in your family if you haven’t been tested). If the doctor doesn’t know this, they may prescribe an iron supplement for your anemia but that’s something you definitely don’t need if you have AT because you may develop ‘iron overload’. Iron overload is harmful.
Microcytosis is the term used to describe red blood cells that are unusually small.
When one parent has two gene changes on the same chromosome and the other parent has no gene changes, for each pregnancy there is a:
- 1 in 2 chance (50%) the baby will have AT trait (two gene changes)
- 1 in 2 chance (50%) the baby won’t have any gene changes.
If both parents have two gene changes on the same chromosome, for each pregnancy there is a:
- 1 in 4 chance (25%) the baby will have AT major (four gene changes)
- 1 in 2 chance (50%) the baby will have AT trait with two gene changes on the same chromosome
- 1 in 4 chance (25%) the baby won’t have any gene changes.
If one parent has gene changes on each chromosome but the other parent has no gene changes, every child will be a carrier.
If both parents have gene changes on each chromosome, every child will have AT trait.
Please check out the other posts of our series here:
Information based on Fast Facts for Patients: Alpha Thalassemia (Karger, 2023).
This is the second part of our series about the condition based on our patient booklet “Fast Facts for Patients: Alpha Thalassemia”. This article explains genes and genetic inheritance as well as one gene change in alpha thalassemia (AT).
Genes and Genetic Inheritance
Genes are carried on chromosomes. Every cell in our bodies has 23 pairs of chromosomes – so 46 in total. Every chromosome carries anywhere from 55 to 20 000 genes.
Genes are in pairs too. You inherit one copy from your mother and one copy from your father. A pair of genes is carried on a pair of chromosomes (one gene on each chromosome). Each pair of genes carries the code to make a single protein. Proteins are chains of chemical building blocks called amino acids and they are vital for the body to function.
Altogether, your genes carry the blueprint for the growth, development and function of your entire body.
Which Genes Are Involved?
Production of the Hb alpha chains is controlled by two pairs of genes – HBA1 and HBA2. The codes they carry are the same.
Each person inherits one copy of each gene from their father and another copy of each gene from their mother. This means that there are four gene copies that can potentially cause AT:
- Two HBA1 genes
- Two HBA2 genes.
Deletional and Non-Deletional Gene Changes
There are two important types of gene change in AT.
- If a gene is completely missing, it is called deletional thalassemia.
- If a gene is not missing but is damaged, it is called non‑deletional thalassemia. Non-deletional gene changes tend to cause more severe symptoms than deletional ones.
Location of Gene Changes
If you have two gene changes, the missing or damaged genes can both be on the same chromosome. This is called a ‘cis’ mutation (gene change). You may see this written as aa/– in your notes.
Or there may be one gene change on each chromosome. This is called a ‘trans’ mutation. You may see this written as a-/a in your notes.
Why Is It Important to Know More about My Condition?
If you are pregnant or planning to become pregnant, it is important to understand more about your genetic condition. Understanding more means you are better informed about the risks to your unborn child.
It is important for parents to know if the gene changes are on the same chromosome or on different chromosomes.
Ask your doctor about your gene changes and write the information down.
One Gene Change
If you have only one AT gene change, you are said to be a silent carrier. This is also called AT minima.
What Does This Mean?
You won’t have any signs of AT and will have no health problems related to it.
If you are a carrier and you have a child with someone who is also a carrier, for each pregnancy there is a:
- 1 in 4 chance (25%) the baby will have AT trait (two gene changes)
- 1 in 2 chance (50%) the baby will be a silent carrier (one gene change)
- 1 in 4 chance (25%) the baby won’t have any gene changes.
Very rarely, and only with certain kinds of gene change, there is a chance of having a child with AT.
Please check out the other posts of our series here:
Information based on Fast Facts for Patients: Alpha Thalassemia (Karger, 2023).
This is the first part of our series about the condition based on our patient booklet “Fast Facts for Patients: Alpha Thalassemia”. This article explains what alpha thalassemia (AT) is, what causes it and who gets it.
First, the Facts
- Alpha thalassemia (AT) is a blood condition you are born with. You have to inherit a gene change from both parents to have AT.
- If you inherit a gene change from one parent, you are a carrier but don’t have the condition. If your partner is also a carrier, you have a chance of having a child with AT.
- AT is most common in people with ancestry from Southeast and South Asia, Africa, the Middle East and around the Mediterranean.
- There are two pairs of genes involved in AT – you may have one, two, three or four gene changes. There are also different types of gene changes – the gene can either be missing or damaged.
- How severe your AT is depends on the number and type of gene changes you have.
- AT major (four gene changes) is typically fatal before or shortly after birth without intervention. It remains a lifelong condition but can now be managed with treatment.
Thalassemia
Thalassemia is a condition you are born with. It affects red blood cells. There are two main types: alpha thalassemia (AT) and beta thalassemia (BT). This post is about AT.
In AT, the body doesn’t make enough healthy hemoglobin (Hb) and there are too few red blood cells. Hb is the protein in red blood cells that enables them to carry oxygen around the body.
Why Isn’t the Hemoglobin Made Properly?
Hb is the protein molecule in red blood cells that carries oxygen from the lungs to the tissues of the body. Carbon dioxide is also transported by Hb from the tissues back to the lungs. Hb helps maintain the shape of a red blood cell.
Normal adult Hb is made up of four protein chains – two alpha chains and two beta chains. If you have AT, your body either makes abnormal alpha chains or doesn’t produce enough of them, so you can’t make enough healthy Hb.
When there aren’t enough healthy red blood cells and Hb, oxygen does not reach the tissues of the body, and a person can feel weak, tired and have difficulty breathing. This is called anemia. It can be mild or serious. Serious anemia can damage organs and can be fatal.
What Causes AT and Who Gets It?
Causes of AT
AT is a genetic condition. This means it is caused by a change (mutation) in one or more genes. There can be different types of change – some cause the alpha chains of Hb to be missing completely, while others cause a decrease in alpha chain production.
AT is more common in some parts of the world where malaria is, or has been, a problem (for example, the Middle East, northern Africa, India and Southeast Asia) and in people with ancestry originating from these areas. This is because the gene changes that cause AT also give some protection against malaria.
Over time, the proportion of people in the population with an AT gene change has increased and, as people migrate around the world, AT has become more common in other regions too.
Types of AT
The type of AT you have and how it affects you depends on:
- how many genes are changed and which ones
- the combination of genes that are affected
- whether each affected gene is completely missing or damaged.
Four Types of AT
Silent carrier. Blood tests are usually normal. You will often have no symptoms, but you can pass the damaged gene on to your child.
Alpha thalassemia minor/trait. You may have mild anemia with small red blood cells that may be mistaken for iron deficiency anemia. Two genes are affected.
Hemoglobin H (HbH) AT. There is just one working alpha gene. You may have moderate to severe anemia. You have a greater risk of having a child with AT major.
Alpha thalassemia major. All four genes are missing. This causes severe anemia. In most cases, a baby with this condition will die before birth unless they are treated in the womb.
Please check out the other posts of our series here:
Information based on Fast Facts for Patients: Alpha Thalassemia (Karger, 2023).
This is the third and last post of a three-part series dealing with the most frequently asked questions about migraine and headache, based on the Karger publication “Migräne & Kopfschmerzen. Ein Fachbuch für Hausärzte, Fachärzte, Therapeuten und Betroffene” (“Migraine & Headache. A Reference Book for General Practitioners, Specialists, Therapists and Persons Concerned”).
This article focuses on and answers seven frequently asked questions about migraine.
Tension headache or migraine?
Tension headaches are usually dull and pressing; migraine headaches are usually strong and pulsating. There are exceptions in both cases, so the accompanying symptoms are the key differentiator.
What does migraine pain typically feel like?
Typical migraine pain is severe, pulsating, one-sided, and disabling in everyday life. However, it can also be less severe, constant, and holocranial, i.e., distributed over the entire head. The most important distinguishing feature from tension headache is the complete absence of accompanying symptoms such as nausea, vomiting, hypersensitivity to light, noise and smell.
Do migraine attacks occur more frequently during menopause?
In general, women are more frequently affected by migraine than men (menstrual migraine, menopausal migraine). In at least one third of all female migraine patients, migraine attacks accumulate before, during or after menstruation, but also around the time of ovulation. Eighty percent of all migraine patients notice a significant decrease in the frequency of migraine attacks during pregnancy. After the birth of the child, they then suffer from migraines again as frequently as before. After menopause, the frequency and severity of migraines usually decrease slowly.
At what age do migraines usually occur?
Most often between the ages of 12 and about 50, but also as early as infancy and old age.
How does a migraine develop?
The development of migraine is now understood as an interaction of several subsystems of the autonomic nervous system, whereby firstly the pain pattern in the head and neck is altered, secondly sensory organs become hypersensitive and thirdly control circuits of the gastrointestinal tract, alertness, blood vessels and other organ systems deviate from their normal function. However, how individual attacks are triggered is still unclear. Dysfunctions of nerve cells seem to be in the foreground.
Is migraine inherited?
Migraine is clearly an inherited predisposition, but it is controlled by numerous known and as yet unknown genes with quite different penetrance. This is a measure of how strongly individual genes actually affect life. Identical twins have a concordance (migraine occurs in both) of about 80%, while in normal siblings this is about 40%. The chance that somebody affected by migraine will have others affected by migraine among first- and second-degree relatives is about 80%. Since migraine is about three times more common among women, maternal inheritance seems to be present, but this is probably an artifact.
How is migraine treated?
Migraine treatment is based on three pillars: 1. attack treatment, 2. drug prophylaxis, 3. complementary medicine prophylaxis. For the treatment of attacks, highly effective triptans are available today, in case the conventionally applied painkillers do not work. Far too many people affected by migraines treat themselves inadequately with conventional painkillers.
Information based on “Migräne & Kopfschmerzen. Ein Fachbuch für Hausärzte, Fachärzte, Therapeuten und Betroffene” (Karger, 2015).
This is the second post of a three-part series dealing with the most frequently asked questions about migraine and headache, based on the Karger publication “Migräne & Kopfschmerzen. Ein Fachbuch für Hausärzte, Fachärzte, Therapeuten und Betroffene” (“Migraine & Headache. A Reference Book for General Practitioners, Specialists, Therapists and Persons Concerned”).
This article gives answers to six frequently asked questions about cluster headaches.
What are cluster headaches?
Cluster headaches are primary headaches because their causes are still unclear. These headaches are exceptionally severe and always occur on the same side of the head. They are accompanied by so-called autonomic signs such as reddened eye, runny nose and others. The attacks are much shorter than in migraine and tension headaches, but often occur several times a day. The word cluster indicates a typical cluster of attacks in the spring. After these episodes, cluster attacks often disappear for months to years.
What are the causes of cluster headaches?
Dilatation or inflammation of blood vessels is not the cause of cluster headache, as previously thought, but rather its consequence. Features of inflammation in the cavernous sinus have not been demonstrated in studies.
Certain pain-conducting pathways in the area of the trigeminal nerve are probably stimulated by as yet unknown influences, leading to a cascade of changes in brain metabolism. The origin of the disorder is thought to be in the hypothalamus or thalamus, two “switching centers” of the diencephalon and, in the case of the hypothalamus, center for the control of major regulatory circuits, such as the sleep-wake rhythm. The diurnal distribution patterns of cluster headaches, the striking frequency of episodes in spring and autumn, and the frequent disturbances in cluster headache patients of hormones that control the diurnal rhythm, such as melatonin, are indicative of such a disturbance.
What factors can trigger a cluster headache attack?
Cluster headache attacks are usually sparked by triggers. These are not the actual cause, but possible triggers of pain attacks. Known triggers are alcohol, histamines, nitroglycerin, flickering or bright light, food additives such as glutamate, potassium nitrite, sodium nitrite, odors (solvents, gasoline, adhesives, perfume), cheese, noise, chocolate, citrus fruits. Other possible triggers: heat, sleep disturbances, sleep apnea syndrome, prolonged exposure to chemicals, extreme anger or emotions, prolonged physical exertion, large changes in altitude. The effect of the various trigger factors varies greatly among patients.
How often do attacks of cluster headache usually occur?
An important feature of cluster headache is that the attacks occur several times a day. Typically, those affected by them report two to four attacks per day, but they may report up to ten or more.
What accompanying symptoms are associated with cluster headache?
Redness of one eye, tearing of the eyes, runny nose, drooping and swollen eyelid, constricted pupil, sweating on the head and others. Apart from sweating, these signs of autonomic nervous system disorder are always on the same side as the headache.
How are cluster headaches treated?
As with most headaches, a distinction must be made between attack and basic treatment. In cluster attacks, the time to onset of action is what counts because of the excruciating pain. Sumatriptan as a subcutaneous injection or pure oxygen via a face mask are the fastest and most effective. The nasal spray zolmitriptan has also proven effective. Before the introduction of sumatriptan, ergotamines were administered intravenously, but these very often led to vomiting and other unpleasant side effects. Intranasal lidocaine 4% can also act very quickly. All tablets are secondary because of the longer absorption time, but can also do a good job.
In basic treatment, i.e., prevention of further attacks, verapamil has gained worldwide acceptance, although very high doses are often necessary under medical supervision. Furthermore, prednisone (mostly initially concomitant until verapamil is increased), topiramate, lithium, melatonin, methysergide, ergotamine, valproate, gabapentin, Botox, electrical stimulators and others. All prophylactics are so-called off-label applications.
Information based on “Migräne & Kopfschmerzen. Ein Fachbuch für Hausärzte, Fachärzte, Therapeuten und Betroffene” (Karger, 2015).
This is the first post of a three-part series dealing with the most frequently asked questions about migraine and headache, based on the Karger publication “Migräne & Kopfschmerzen. Ein Fachbuch für Hausärzte, Fachärzte, Therapeuten und Betroffene” (“Migraine & Headache. A Reference Book for General Practitioners, Specialists, Therapists and Persons Concerned”).
This article provides answers to six frequently asked questions about tension headaches.
Tension headache or migraine?
Tension headaches are usually dull and pressing; migraine headaches are usually strong and pulsating. There are exceptions in both cases, so the accompanying symptoms are the key differentiator.
How do tension-type headaches typically manifest themselves?
When it comes to the perception of tension-type headaches, the rule is that the pain is constant, moderately severe, and distributed over the entire head. However, pulsating and disabling pain also occurs. The most important distinguishing feature from migraine is the complete absence of accompanying symptoms such as nausea, vomiting, hypersensitivity to light, noise, and smell. Tension headache (also often referred to as tension-type headache) can be briefly summarized as “pure headache”. Tension headache is the most common type of headache of all and occurs as an attack headache, but also as a chronic, constant daily headache.
Are neck tensions the cause of tension headache?
Neck tension is rather rarely a cause of headache. Similar to migraine, it is often difficult to distinguish whether the neck tension is the cause of the headache or whether it is merely an accompanying pain in the neck. Tension headaches can be divided into those with and those without muscular tension in the head and neck region. However, this distinction does not seem to help in terms of cause or treatment.
When do we speak of chronic tension headaches?
The term “chronic” is ambiguous: On the one hand, it refers to the duration of the headache, i.e., at least three months; on the other hand, it is much more significant how many days per month a headache is present, i.e., at least 15 days per month.
What favors the development of tension headache?
In the foreground is an individual tendency to react to internal and external stimuli with headaches, migraines or tension headaches. These are often an expression of overload, self-inflicted as well as externally inflicted. Typically, tension headaches develop during the day, indicating increasing fatigue. This is aggravated by sleep problems, depressive moods and psychosocial problems. If sleep problems, alcohol consumption, medication overuse are suspected as causes, they are so-called secondary headaches.
How often may one take tablets for tension headaches?
“May” implies, on the one hand, medical limits in the use of tablets, but also, not insignificantly, socio-psychological rules and a kind of moral prescription. Medical limits for “may” would be, for example, that paracetamol should not exceed the daily total of four grams per day, because otherwise this exceeds the capacity of the liver to break down paracetamol. Frequently exceeding four grams per day can cause severe liver damage. Or, depending on individual predisposition, acetylsalicylic acid can cause spontaneous bleeding and stomach problems. The triptans, however, know no such critical side effects. With “may” in the socio-psychological sense is also connected a kind of bad conscience and fear (e.g. of addiction and dependence).
Apart from side effects probably all attack medications can lead to medication overuse headache (MOH), if a certain number of takings per month occurs. One speaks of MOH with pain medicines and related medicines starting from 15 tablets or administrations per month, while with triptans already starting from 10 applications per month.
Information based on “Migräne & Kopfschmerzen. Ein Fachbuch für Hausärzte, Fachärzte, Therapeuten und Betroffene” (Karger, 2015).
This is the eleventh part of our series about the condition based on our patient booklet “Fast Facts for Patients: Waldenström Macroglobulinemia”. This article shows what to do when Waldenström macroglobulinemia (WM) comes back. Furthermore, approaches in research as well as new treatments are addressed.
When WM Comes Back
When WM comes back, it can be treated again. The type of treatment will depend on the effects of previous treatments, how long it is since the last course of treatment and your general health. The same treatment can be used again if a year or more has passed since its initial use.
If the WM relapses more quickly than this, a different drug or a combination of drugs or a stem cell transplant might be considered.
In most people with WM, relapsed disease responds well to treatment and further remissions can be expected.
High-Grade Transformation
In a small number of people, WM turns into a faster-growing type of lymphoma. If this happens, it usually causes new symptoms and is detected by tests such as a lymph node biopsy. This is called transformation and, although it sounds worrying, it can be treated using more intensive chemotherapy that is normally used for high-grade lymphomas.
Active Monitoring
It is very important that all treatment decisions are made with good judgment and care. A new treatment should be started for clinical reasons (symptoms) and not at the first sign that the IgM paraprotein level is rising.
The time it takes for a relapse to result in symptoms can span many months or even a few years. So, in the absence of emergency situations such as hyperviscosity, you may have a period of active monitoring that lasts a few months before treatment is started.
Research and New Treatments
Clinical Trials
You may be asked if you would like to take part in a clinical trial. Clinical trials are research studies that test new medical treatments or different combinations of existing treatments.
Some newer treatments are only available in a clinical trial. Not all hospitals take part in clinical trials and there may not be a trial that is suitable for you when you are diagnosed or relapse, but this is something to discuss with your specialist when planning treatment.
You do not have to take part in a clinical trial – you can always opt to have the standard treatment instead.
Studying Genetic Changes
Research is looking at the significance of genetic mutations such as MYD88 and CXCR4 mutations to see if medications can target them to disrupt the disease. Other genetic changes have been identified and are also being studied.
CAR T-Cell Therapy
You may have heard about a new type of treatment called CAR T-cell therapy (CAR stands for chimeric antigen receptor). It is currently being developed to treat different types of B-cell leukemia and lymphoma, but it is not yet a viable option for patients with WM.
Registry Data
Apart from clinical trials of new therapies, efforts are under way to capture so-called “real-world data” using registries, which are comprehensive electronic databases with data protection measures in place. In a rare condition like WM, this kind of evidence can help researchers understand how people live with their WM, and the effects of different treatments on their WM and their lives. This information can also help healthcare funders decide on the value of treatments in the care of patients.
Check out the other posts of our series here:
Information based on Fast Facts for Patients: Waldenström Macroglobulinemia (Karger, 2022).
This is the tenth part of our series about the condition based on our patient booklet “Fast Facts for Patients: Waldenström Macroglobulinemia”. This blog posts focuses on supportive treatments for Waldenström macroglobulinemia (WM).
Supportive treatments are designed to counteract some of the symptoms of the disease and the side effects of treatment. In WM, supportive treatments include antibiotics to prevent infections (which may occur during chemotherapy cycles), blood transfusions, iron infusions, and plasmapheresis and intravenous immunoglobulin (IVIG).
Iron Replacement
Iron is crucial for many bodily processes, including the production of red blood cells. In some people with WM, iron is not used correctly in the body. This can lead to anemia, even if there is not a large number of LPL cells in the bone marrow.
Taking iron in tablet form (oral) or in the form of a drip into the vein (intravenous) may be helpful in these circumstances. Receiving iron replacement can boost the hemoglobin and improve energy levels, delaying the need to start chemotherapy. It is important that other causes of iron deficiency (such as bleeding) are excluded first, though. Intravenous iron given once or twice a week apart is generally more effective than taking iron orally.
Blood Transfusions
Your blood counts can decrease as a result of the WM itself or because chemotherapy is affecting your bone marrow as a side effect. If the counts fall to levels that cause troublesome symptoms, the medical team will consider giving you red blood cell or platelet transfusions. Transfusions are given through a cannula (a thin flexible tube) into a vein; this can be done either as a day case or as an inpatient.
Growth Factors
Having a low white blood cell count increases the risk of infection. White blood cells cannot be given by transfusion. Instead, growth factors can be used to boost the number of white blood cells. Growth factors are given by injection under the skin (subcutaneous) – the number of injections needed depends on individual circumstances.
Plasmapheresis or Plasma Exchange
Plasmapheresis can help with the effects of hyperviscosity which develops in up to 3 in 10 people with WM. It causes symptoms that may include nosebleeds, blurring or loss of vision, dizziness, headaches, drowsiness, poor concentration, confusion and shortness of breath.
During plasma exchange, you are hooked up to a sophisticated machine via two of your veins. Your blood leaves your body from one vein, is processed by the closed system in the machine and returned to your bloodstream through the other vein. The outpatient process typically takes 3–4 hours and is carried out in a specialist unit.
Your clinical team will work out how many plasma exchanges you need, and how often, before you start to have your main treatment.
Prevention of Infection
If you are receiving chemotherapy you may need to take medications to help prevent bacterial, viral and fungal infections as your immune system may be temporarily weakened.
This may involve taking an antibiotic, antiviral or antifungal medication. Prescribing of these varies in different centers. Sometimes a short-term antibiotic is needed, for example before an invasive dental or surgical procedure.
Vaccinations
It is important to get all the vaccines that your doctor recommends.
You should be offered pneumococcal vaccination in the form of pneumococcal conjugate vaccine followed by pneumococcal polysaccharide vaccine at least 2 months later (this is the guidance in the UK – it may differ in other countries). If you develop recurrent infections, you may benefit from a wider range of vaccines against other bacteria that cause pneumonia and meningitis.
Live vaccines against polio, herpes zoster (shingles) and yellow fever are not recommended. However, there is a non-live vaccine against herpes zoster that is approved for use in immunocompromised patients. Ask your doctor about this.
Individuals with blood cancer can be vaccinated against COVID-19 as the vaccines do not pose a risk of infection. If you are receiving chemotherapy or immunosuppression, talk to your hospital doctor about when to get vaccinated. You may respond less well to vaccines if your immune system is diminished by your WM or treatment.
Intravenous Immunoglobulin
If you are less able to produce antibodies in response to infection because of your WM or your treatment, you may experience recurrent infections, such as chest infections, sinus infections or bladder infections. If you develop back-to-back infections and require repeated courses of antibiotics or admissions to hospital, then ask your doctor to check your immunoglobulin levels.
Your immunoglobulin levels give a measure of your capacity to produce antibodies. If they are low, in particular if your IgG level is less than 4 g/L, you may benefit from IVIG infusions, which can be given monthly into a vein.
IVIG consists of antibodies extracted from blood donations that have gone through manufacturing steps to the risk of transmitting an infection.
IVIG is a precious resource that is in short supply, so your case for receiving it is likely to be assessed by a panel of experts. Certain conditions need to be met, such as vaccination against bacterial infections, as mentioned above. Once IVIG is started, its use is limited to the smallest effective dose, frequency and duration.
Check out the other posts of our series here:
Information based on Fast Facts for Patients: Waldenström Macroglobulinemia (Karger, 2022).
