Researchers from the United States involved in a meta-analysis have reported that allogeneic stem cell transplants in first complete remission improves survival for patients with intermediate- and poor-risk acute myeloid leukemia (AML). The details of this study appeared in the June 10, 2009 issue of the Journal of the American Medical Association.[1]

Patients with newly diagnosed AML who achieve a complete remission following remission induction therapy have historically been advised to receive consolidation treatment with either high-dose chemotherapy supported by an allogeneic HLA-matched sibling stem cell transplant, high-dose chemotherapy and autologous stem cell transplant, or conventional-dose chemotherapy delivered without stem cell support. Patients currently receive one of these consolidation treatment strategies based on their perceptions of the outcomes associated with each treatment, the availability of an HLA-matched sibling stem cell donor, their physician’s bias concerning the appropriateness of each treatment option, and the geographic availability of each treatment.

One important limitation of allogeneic stem cell transplantation is that such therapy is usually limited to patients 60 years of age or younger. This means that the majority of patients will not be given this option because the average age at diagnosis for AML is 67 years and rising as the population ages. However, recent progress in the use of reduced intensity allogeneic stem cell transplants may allow this treatment to be administered safely to older patients. Another development that has already had a major impact is the observation that recipients of unrelated donor and umbilical cord blood transplants have survivals equivalent to those receiving sibling transplants, which greatly increases the number of patients who can be treated with a stem cell transplant.

Despite the initial choice of consolidation therapy, it is important to determine the availability of a marrow or stem cell donor as soon as possible following the initial diagnosis of AML. This allows for an immediate transplant if remission induction is a failure and defines therapeutic options once a remission is achieved.

Previous analyses have suggested that allogeneic stem cell transplants do not benefit patients with good-risk AML and that such therapy should be reserved for patients who relapse.

The current study was a meta-analysis of 24 prospective trials where patients with AML in first complete remission were assigned to receive an allogeneic stem cell if a compatible donor was available; those without a compatible donor received an autologous stem cell transplant or intensive chemotherapy consolidation. This study included over 5,000 patients, and over 3,000 had cytogenetics that allowed risk assessment. These authors made the following observations:

• Patients with poor-risk AML who were recipients of allogeneic stem cell transplants had a 31% improvement in relapse-free survival and a 27% improvement in overall survival compared with non-transplant patients.
• Patients with intermediate-risk AML who were recipients of allogeneic stem cell transplants had a 24% improvement in relapse-free survival and a 17% improvement in overall survival compared with non-transplant patients.
• Patients with good-risk AML who were recipients of allogeneic stem cell transplants had a 6% worse relapse-free survival and a 7% worse survival compared with non-transplant patients.

Comments: These data confirm other studies suggesting that good-risk patients with AML do not benefit from a stem cell transplant while in first remission and that such treatment should be reserved for treatment failures. These studies also suggest that there is benefit from performing a transplant in first remission for intermediate- and poor-risk patients when compared with non-transplant treatment in patients who do not have donors. However, it should be pointed out that for a patient with an identified marrow donor, the question is not whether transplant in first remission is better than conventional treatment in patients who do not have donors; the question is whether or not the survival rate for transplantation in first remission is better than the combined survival rate following chemotherapy consolidation plus salvage stem cell transplant in those who relapse. A randomized trial to answer this question has been discussed for 20 years but has never been carried out.

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