Myeloablative versus reduced-intensity hematopoietic cell transplantation for acute myeloid leukemia and myelodysplastic syndromes

Bart L. Scott, Marcelo C. Pasquini, Brent R. Logan, Juan Wu, Steven M. Devine, David L. Porter, Richard T. Maziarz, Erica D. Warlick, Hugo F. Fernandez, Edwin P. Alyea, Mehdi Hamadani, Asad Bashey, Sergio Giralt, Nancy L. Geller, Eric Leifer, Jennifer Le-Rademacher, Adam M. Mendizabal, Mary M. Horowitz, H. Joachim Deeg, Mitchell E. Horwitz

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204 Scopus citations

Abstract

Purpose The optimal regimen intensity before allogeneic hematopoietic cell transplantation (HCT) is unknown. We hypothesized that lower treatment-related mortality (TRM) with reduced-intensity conditioning (RIC) would result in improved overall survival (OS) compared with myeloablative conditioning (MAC). To test this hypothesis, we performed a phase III randomized trial comparing MAC with RIC in patients with acute myeloid leukemia or myelodysplastic syndromes. Patients and Methods Patients age 18 to 65 years with HCT comorbidity index#4 and,5% marrow myeloblasts pre-HCT were randomly assigned to receive MAC (n = 135) or RIC (n = 137) followed by HCT from HLAmatched related or unrelated donors. The primary end point was OS 18 months post-random assignment based on an intent-to-treat analysis. Secondary end points included relapse-free survival (RFS) and TRM. Results Planned enrollment was 356 patients; accrual ceased at 272 because of high relapse incidence with RIC versus MAC (48.3%; 95% CI, 39.6% to 56.4% and 13.5%; 95% CI, 8.3% to 19.8%, respectively; P <.001). At 18 months, OS for patients in the RIC arm was 67.7% (95% CI, 59.1% to 74.9%) versus 77.5% (95% CI, 69.4% to 83.7%) for those in the MAC arm (difference, 9.8%; 95% CI, 20.8% to 20.3%; P = .07). TRM with RIC was 4.4% (95% CI, 1.8% to 8.9%) versus 15.8% (95% CI, 10.2% to 22.5%) with MAC (P = .002). RFS with RIC was 47.3% (95% CI, 38.7% to 55.4%) versus 67.8% (95% CI, 59.1% to 75%) with MAC (P <.01). Conclusion OS was higher with MAC, but this was not statistically significant. RIC resulted in lower TRM but higher relapse rates compared with MAC, with a statistically significant advantage in RFS with MAC. These data support the use of MAC as the standard of care for fit patients with acute myeloid leukemia or myelodysplastic syndromes.

Original languageEnglish (US)
Pages (from-to)1154-1161
Number of pages8
JournalJournal of Clinical Oncology
Volume35
Issue number11
DOIs
StatePublished - Apr 10 2017

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Scott, B. L., Pasquini, M. C., Logan, B. R., Wu, J., Devine, S. M., Porter, D. L., Maziarz, R. T., Warlick, E. D., Fernandez, H. F., Alyea, E. P., Hamadani, M., Bashey, A., Giralt, S., Geller, N. L., Leifer, E., Le-Rademacher, J., Mendizabal, A. M., Horowitz, M. M., Deeg, H. J., & Horwitz, M. E. (2017). Myeloablative versus reduced-intensity hematopoietic cell transplantation for acute myeloid leukemia and myelodysplastic syndromes. Journal of Clinical Oncology, 35(11), 1154-1161. https://doi.org/10.1200/JCO.2016.70.7091