Myeloablative Versus Reduced-Intensity Hematopoietic Cell Transplantation for Acute Myeloid Leukemia and Myelodysplastic Syndromes
Top Cited Papers
- 10 April 2017
- journal article
- research article
- Published by American Society of Clinical Oncology (ASCO) in Journal of Clinical Oncology
- Vol. 35 (11), 1154-1161
- https://doi.org/10.1200/jco.2016.70.7091
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 HLA-matched 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, −0.8% 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.Keywords
This publication has 33 references indexed in Scilit:
- Similar outcomes using myeloablative vs reduced-intensity allogeneic transplant preparative regimens for AML or MDSBone Marrow Transplantation, 2011
- Nonmyeloablative Allogeneic Hematopoietic Cell Transplantation in Patients With Acute Myeloid LeukemiaJournal of Clinical Oncology, 2010
- Hematopoietic cell transplantation–specific comorbidity index as an outcome predictor for patients with acute myeloid leukemia in first remission: combined FHCRC and MDACC experiencesBlood, 2007
- Comparable non-relapse mortality and survival after HLA-identical sibling blood stem cell transplantation with reduced or conventional-intensity preparative regimens for high-risk myelodysplasia or acute myeloid leukemia in first remissionBone Marrow Transplantation, 2007
- Comparison between two fludarabine-based reduced-intensity conditioning regimens before allogeneic hematopoietic stem-cell transplantation: fludarabine/melphalan is associated with higher incidence of acute graft-versus-host disease and non-relapse mortality and lower incidence of relapse than fludarabine/busulfanLeukemia, 2007
- Impact of Cytogenetics on Outcome of De Novo and Therapy-Related AML and MDS after Allogeneic TransplantationTransplantation and Cellular Therapy, 2007
- Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasiaBlood, 2006
- Allogeneic hematopoietic stem-cell transplantation in AML and MDS using myeloablative versus reduced-intensity conditioning: the role of dose intensityLeukemia, 2005
- Myeloablative vs nonmyeloablative allogeneic transplantation for patients with myelodysplastic syndrome or acute myelogenous leukemia with multilineage dysplasia: a retrospective analysisLeukemia, 2005
- Evidence for a graft-versus-leukemia effect after allogeneic peripheral blood stem cell transplantation with reduced-intensity conditioning in acute myelogenous leukemia and myelodysplastic syndromesBlood, 2002