Myeloablative vs Reduced-Intensity HCT for Acute Myeloid Leukemia and Myelodysplastic Syndromes


Key Points

  • In patients with acute myeloid leukemia and myelodysplastic syndromes, myeloablative conditioning was associated with significantly improved relapse-free survival and a nonsignificant overall survival benefit.
  • Reduced-intensity conditioning was associated with a lower rate of treatment-related mortality.

In a phase III trial reported in the Journal of Clinical Oncology, Scott et al found that myeloablative conditioning for allogeneic hematopoietic cell transplantation was associated with a reduced risk of relapse and a nonsignificant overall survival advantage vs reduced-intensity conditioning in patients with acute myeloid leukemia and myelodysplastic syndromes. Study accrual was stopped prematurely based on the finding of an increased relapse risk with reduced-intensity conditioning. It had been hypothesized that lower treatment-related mortality with reduced-intensity conditioning would result in better overall survival.

Study Details

In the open-label trial, 272 patients (of a target enrollment of 356 patients) aged 18 to 65 years with a transplantation comorbidity index ≤ 4 and < 5% marrow myeloblasts pretransplantation were randomized to receive myeloablative conditioning (n = 135) or reduced-intensity conditioning (n = 137) followed by transplantation from human leukocyte antigen (HLA)-matched related or unrelated donors. The study opened in June 2011 and was closed to accrual in April 2014 on data and safety monitoring board recommendation due to a large difference in relapse-free survival favoring myeloablative conditioning. The primary endpoint was overall survival 18 months postrandomization in the intent-to-treat population.

Poorer Relapse-Free Survival

Relapse was observed in 48.3% of the reduced-intensity conditioning group vs 13.5% of the myeloablative conditioning group (P < .001). At 18 months, overall survival was 67.7% vs 77.5% (difference = 9.8%, P = .07). Treatment-related mortality was 4.4% vs 15.8% (P = .002). Relapse-free survival at 18 months was 47.3% vs 67.8% (P < .01), respectively.

Among 110 patients in the reduced-intensity conditioning group and 108 patients in the myeloablative conditioning group with acute myeloid leukemia, 18-month relapse-free survival was 45.3% vs 65.2% (P = .003), and overall survival was 63.4% vs 76.4% (P = .035). Among 27 patients with myelodysplastic syndromes in each group, 18-month relapse-free survival was 55.6% vs 77.8% (P = .07), and overall survival was 85.2% vs 81.5% (P = .175). The cumulative incidence of relapse was 51% vs 15.9% among patients with acute myeloid leukemia and 37% vs 3.7% among patients with myelodysplastic syndromes.

The investigators concluded: “[Overall survival] was higher with [myeloablative conditioning], but this was not statistically significant. [Reduced-intensity conditioning] resulted in lower [treatment-related mortality] but higher relapse rates compared with [myeloablative conditioning], with a statistically significant advantage in [relapse-free survival] with [myeloablative conditioning]. These data support the use of [myeloablative conditioning] as the standard of care for fit patients with acute myeloid leukemia or myelodysplastic syndromes.”

The study was supported by the National Heart, Lung, and Blood Institute, the National Cancer Institute, and the National Institutes of Health.

Bart L. Scott, MD, of Fred Hutchinson Cancer Research Center, is the corresponding author of the Journal of Clinical Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.