Early Allogeneic Stem Cell Transplants Benefit Intermediate-Risk AML
French researchers have reported that allogeneic stem cell transplants in first complete remission (CR) benefit intermediate-, but not good- or poor-risk patients with acute myeloid leukemia (AML). The details of an analysis of 17 years of study were presented at the 2005 Tandem BMT meetings in Keystone Colorado, February 10-14, 2005.
Acute myeloid leukemia (AML) is a cancer of the bone marrow and blood characterized by the uncontrolled growth of immature white blood cells (immune cells), which never develop into functioning cells. Besides not being able to carry out the functions of mature immune cells, AML cells may also crowd out normal blood cells in the bone marrow and blood. AML is considered to be an aggressive cancer and patients are often at a high risk of developing a cancer recurrence following therapy, particularly if they are not able to undergo high doses of therapy. Chromosomal variables of AML cells, as well as levels of cancer cells in the blood, further distinguish patients into being at a high-risk, standard-risk or low-risk of developing a cancer recurrence and treatment may be altered according to these stratifications.
Patients with AML first undergo “induction therapy” to produce a complete remission, which is defined as disappearance of leukemia cells in the bone marrow and normalization of the white blood cell, red blood cell and platelet levels. All patients with AML would experience a return of their cancer if they received no further therapy after induction therapy. Most patients now receive additional treatment following induction therapy, referred to as consolidation therapy. One option of consolidation therapy is an allogeneic stem cell transplant, which is the utilization of high doses of therapy followed by the infusion of donor stem cells. The high doses of therapy kill more cancer cells than conventional doses of therapy, but are associated with higher rates of severe side effects and treatment-related deaths. However, allogeneic stem cell transplants used as consolidation therapy in patients with AML result in a reduction in cancer recurrences compared to other consolidation therapies. Due to the higher rates of treatment-related deaths and severe side effects associated with an allogeneic stem cell transplant, researchers continue to evaluate which patients derive the greatest benefit from this therapeutic approach.
Researchers in France have evaluated the outcomes of patients with AML under the age of 45 years who were assigned to receive an allogeneic stem cell transplant in first CR. All patients had a compatible donor. The outcomes of patients undergoing allogeneic stem cell transplants were compared to outcomes of patients who were treated with an autologous stem cell transplant, a procedure in which a patient’s stem cells are re-infused following high doses of therapy, following induction therapy, or just additional chemotherapy after induction therapy. Based on the risk factors of initial white blood cell counts, FAB subtypes (based on how the cells look under the microscope), cytogenetic risk group (specific types of chromosome abnormalities) and number of induction courses to achieve a CR patients were categorized as poor, intermediate or standard risk. The median follow-up was 10 years.
Overall survival was improved in the group of patients that was considered to be intermediate risk who underwent an allogeneic stem cell transplant as consolidation therapy (56%), compared to those treated not treated with an allogeneic stem cell transplant as consolidation therapy (41%). Although patients with good or poor-risk AML had improved outcomes with an allogeneic stem cell transplant compared to other consolidation therapies, the improvement was not marked.
Patients with AML who have a stem cell donor, particularly those with intermediate-risk AML, should discuss their individual risks and benefits, as well as optimal timing of an allogeneic stem cell transplant with their physicians.
Reference: Jourdan E, Boidron JM, Dastugue N, et al. Ealrly allogeneic stem cell transplantation for young adults with acute myeloblastic leukemia in first complete remission: An intent-to-treat analysis of the long term experience of the BGMT group. Biology of Blood and Marrow Transplantation. 2005;11, number 2, supplement 1:17, abstract number 49.
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