Treatment Options for Acute Myelogenous Leukemia

Stem Cell Transplantation for Acute Myelogenous Leukemia

What are Stem Cells?

Stem cells are immature, special cells located in the bone marrow (the spongy material found inside long-bones) that mature into the three major types of blood cells:

• Red blood cells - carry oxygen to all tissues and organs of the body
• White blood cells - components of the body's immune system responsible for fighting infections
• Platelets - specialized cells in the bloodstream that are responsible for clotting of blood (stop bleeding when a person sustains a cut or an injury to blood vessels)

High-dose chemotherapy used to destroy cancer cells, unfortunately, also kills most the patient's blood-forming bone marrow and stem cells. Without these critical cells, the patient is susceptible to a variety of potentially life-threatening problems including increased susceptibility to infections and bleeding complications. Bone marrow and stem cell transplantation enables doctors to replace the critical blood-forming cells after high-dose chemotherapy to kill cancer cells has been completed.

The source of stem cells used for transplantation is either bone marrow usually harvested (removed) from the hip bone (bone marrow transplantation) or the stem cells can be obtained from the peripheral bloodstream via a procedure called apheresis (peripheral blood stem cell transplantation). In both cases, the stem cells are frozen and stored for later use until the patient has completed their course of high-dose chemotherapy and are then administered to the patient by intravenous infusion. For the purposes of this discussion the terms "bone marrow transplantation" and "stem cell transplantation" are used interchangeably.

The Role of Stem Cell Transplantation in Acute Myelogenous Leukemia

Stem cell transplantation allows the use of very high doses of chemotherapy while preserving the blood-producing stem cells. Stem cells are collected either from the bone marrow or the bloodstream of either the individual patient or a suitable donor (related or not related). The type of stem cell transplantation (autologous - from the patient or allogeneic - from another person) and the timing are determined after comprehensive analysis of the subtype of acute myelogenous leukemia (AML), patient age and performance status, cytogenetics, availability of appropriate stem cells, as well as other factors.

Following chemotherapy, with or without whole body radiation, the stored stem cells ("graft") are given to the person as a blood transfusion. Usually around 14-21 days after the graft infusion, the stem cells begin making red blood cells, white blood cells, and platelets. When stem cells from a donor are used (allogeneic transplant), drugs are given to prevent rejection of the graft or graft-vs-host disease - a potentially fatal condition in which the graft mediates damage to the host's intestines, liver, and skin.

Considerable debate has taken place regarding the advisability of a stem cell transplant, rather than continued chemotherapy without stem cell transplantation, when the patient enters complete remission. In general the data accumulated so far suggests that survival is similar with both approaches. Thus, while stem cell transplantation appears to decrease the risk of relapse of acute myelogenous leukemia, it also increases the chance of death in complete remission, with these balancing out to yield equivalence in survival. An important question is whether some patients would do better with, while others without, a stem cell transplant.

Patients with acute promyelocytic leukemia or core-binding factor AML are so unlikely to relapse with chemotherapy alone that the risk of stem cell transplantation in first complete remission is difficult to justify. In contrast, very young patients (less than age 18) have such a low-risk of transplant-related mortality that an allogeneic stem cell transplant in first complete remission is very reasonable. For the remaining (the majority) of patients, the outcome is dictated more by the characteristics of the AML (e.g. the cytogenetics) rather than by the treatment. Thus, there is considerable need for developing new approaches to stem cell transplantation as well as for chemotherapy. One new approach is called a "mini- transplant", also known as a non-myeloablative transplant or reduced-intensity transplant. The doses of chemotherapy used for a "mini-transplant" are significantly lower than with a standard allogeneic stem cell transplant, with reliance placed on the ability of the graft to kill AML cells ("graft-vs-leukemia"). Consequent to the reduction in dose, a "mini-transplant" is feasible in patients who have been considered ill-suited for a standard allogeneic transplant either because of advanced age (60 years or older) or other underlying problems such as ongoing infection. Whether the reduction in toxicity associated with a "mini-transplant" will result in a corresponding reduction in efficacy for the treatment of acute myelogenous leukemia is unknown at this time.