Nonmyeloablative Transplantation

Similar to the situation in ALL, nonmyeloablative transplantation for AML has been shown to reduce transplant-related morbidity and mortality, mainly by reducing the incidence of serious complications in the immediate posttransplant period. Here as well, the GVL reaction is an important component of therapy. The Spanish Group for Hematopoietic Transplantation demonstrated a significant improvement in outcome for patients who developed grade II-IV acute GVHD in comparison with patients who experienced no GVHD after nonmyeloablative transplantation (13 vs 58% disease progression at 1 year, p = 0.008).88

The use of transplantation for patients with AML in first remission has been demonstrated to be safe. Feinstein et al. transplanted 18 patients with AML in first remission and demonstrated that nonrelapse mortality was only 17% at 1 year. The majority of treatment failures in this cohort were related to disease relapse, which was responsible for 70% of the deaths in this trial.89 Nonmyeloablative transplantation has been used as consolidation therapy for patients in second remission, for relapsed disease after failed autolo-gous transplantation or prior high-dose allogeneic stem cell transplantation and for patients with refractory leukemia. In these settings, the most important predictors of long-term outcome include cytogenetics and remission status at the time of transplantation.

To explore the utility of nonmyeloablative transplantation in a cohort of individuals traditionally considered eligible for ablative transplantation approaches, Ruiz-Arguelles et al. transplanted 24 young patients (median age 35 years) with AML, using nonmyeloablative conditioning.90 The median survival of this cohort exceeds 7 years and has not been reached and progression-free survival at 2 years is 66%. Transplant-related toxicity was very minor, and the majority of transplants occurred in an outpatient setting. Similarly, Alyea et al. compared the results of ablative and nonmyeloablative conditioning in a cohort of individuals above the age of 50, the majority of whom had AML. No differences in outcome were noted; however, interestingly, it appeared that patients <50 years did better with ablative regimens.91 While results from larger series need to confirm these findings, the combination of reduced treatment-related morbidity and mortality with an active GVL effect may make nonmyeloablative transplantation the therapy of choice for individuals in first remission with either intermediate or unfavorable cytogenetic risks, but is not recommended routinely at this time.

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