In a study reported in the Journal of Clinical Oncology, Hourigan et al found that reduced-intensity conditioning for allogeneic hematopoietic cell transplantation was associated with poorer outcomes vs myeloablative conditioning in patients with acute myeloid leukemia (AML) who had genomic evidence of residual disease.

Study Details

The study included data from 190 of 218 patients with AML enrolled in a phase III trial comparing outcomes by conditioning intensity in adult patients with myeloid malignancy undergoing allogeneic hematopoietic cell transplantation while in morphologic complete remission. Ultra-deep next-generation sequencing (NGS) for 13 commonly mutated genes in AML was performed on preconditioning blood from 95 patients who had received reduced-intensity conditioning and 95 who had received myeloablative conditioning.

Key Findings

Among the 32% of patients in the myeloablative conditioning group and the 37% of patients in the reduced-intensity conditioning group without detected mutations, 3-year overall survival was 56% vs 63% (P = .96). Among patients who were NGS-positive for mutations, myeloablative conditioning was associated with reduced 3-year cumulative incidence of relapse (19% vs 67%, P < .001) and improved 3-year overall survival (61% vs 43%, P = .02).

In multivariable analysis among NGS-positive patients that adjusted for disease risk and donor group, reduced-intensity conditioning was associated with increased risk of relapse (hazard ratio [HR] = 6.38, P < .001), poorer relapse-free survival (HR = 2.94, P < .001), and poorer overall survival (HR = 1.97, P = .01) vs myeloablative conditioning.

The investigators concluded: “This study provides evidence that myeloablative conditioning rather than reduced intensity conditioning in patients with AML with genomic evidence of [minimal residual disease] before allogeneic hematopoietic cell transplantation can result in improved survival.”

Christopher S. Hourigan, DM, DPhil, of the Laboratory of Myeloid Malignancies, National Heart, Lung, and Blood Institute, National Institutes of Health, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by the Intramural Research Program of the National Heart, Lung, and Blood Institute and the National Cancer Institute. For full disclosures of the study authors, visit ascopubs.org.