What Happens in Acute Myeloid Leukemia?

Acute myeloid leukemia (AML) is an aggressive form of cancer that affects the precursor of many types of blood cells including cells that transport oxygen (red blood cells), fight infection (neutrophils), and help the blood clot and heal wounds (platelets). Since the precursor cells multiply a lot or, in other words, become cancerous and occupy the bone marrow, the production of these important blood cells is affected. Consequently, the symptoms of acute myeloid leukemia are tiredness due to anemia, risk of bleeding, and increased risk of infections.

Being an acute type of cancer, acute myeloid leukemia requires immediate treatment. Chemotherapy is the main first line of treatment method. Drugs, radiotherapy, and bone marrow transplant are recommended based on the condition. These therapies are often combined with blood transfusion since blood count will be low as well as antibiotics to reduce the risk of infections.

Refractory Acute Myeloid Leukemia

For acute myeloid leukemia, generally, 1 to 2 cycles of primary induction chemotherapy are administered to patients to start observing remission. However, being a complex disease, even after the standard treatment methods, some patients do not reach complete remission where all the signs and symptoms of the disease go away. The disease is now called refractory acute myeloid leukemia. In other cases, there can be a recurrence of cancer after the remission which is termed relapsed cancer.

These conditions, especially refractory acute myeloid leukemia, require assessing and modulating further treatment steps and are called salvage therapy. The options are limited for salvage therapy with the main method being intensive chemotherapy with modified regimens. A curative technique considered is stem cell transplant using cells derived from healthy donors. This technique is called allogeneic hematopoietic stem cell transplantation.

The new stem cells introduced from a healthy donor through the stem cell transplant can help in replacing diseases and damaged marrow and potentially even fight the cancer cells. The main disadvantage of using donor cells, even after careful matching to the recipient, is that there is always a risk of immune response and rejection of the foreign cells. Hence, in most cases, the bone marrow transplant is not considered when not in remission.

Stem Cell Transplantation and Salvage Chemotherapy

For both refractory and relapsed leukemia, the question that arises is which is the best treatment option? While the mainstay is salvage chemotherapy, the latest study, “Chemotherapy or Allogeneic Stem Cell Transplantation as Salvage Therapy for Patients with Refractory Acute Myeloid Leukemia: A Multicenter Analysis”, asks the question whether stem cell transplant without salvage chemotherapy can be considered.

The group looked at treatment information and outcome of 220 patients who had refractory or relapsed acute myeloid leukemia. Of these patients, 191 were given salvage chemotherapy treatment and only 42% achieved complete remission. Among the remaining 29 patients who were directly given stem cell transplants without any salvage chemotherapy, around 90% reached complete remission. When those given stem cell transplants were further monitored, the survival rate of these patients over 4 years (called 4-year survival rate) was close to 52%. This showed that stem cell transplant can be effective.

Even among those patients who were first given salvage chemotherapy, when it was followed by stem cell transplant their 4-year survival rate was 36–46% compared to a rate of 3–11% without transplant treatment. In short, if the first line of treatment for these patients was salvage chemotherapy, then following it with a stem cell transplant increased their chances of 4-year survival considerably.

The main caveat of the study was the number of patients, especially those who underwent direct stem cell transplants. Secondly, the fact that the study was done in retrospect means that it will be hard to make a direct comparison of different conditions and procedures. It is important to do these in larger-scale studies to conclusively change treatment recommendations for now.

Take-Home Message

Acute myeloid leukemia is a difficult disease to treat. There are some standard lines of chemotherapy and stem cell transplant treatments, along with new lines of treatment being developed. However, through different studies, the order and administration of these treatments to attain better outcomes have to be considered. For now, based on the study described above, it can be said that stem cell transplantation without salvage chemotherapy is an option that clinicians should consider when treating patients with refractory or relapsed acute myeloid leukemia.