Augmented Reduced-Intensity Regimen Does Not Improve Postallogeneic Transplant Outcomes in Acute Myeloid Leukemia
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Open Access
- 1 March 2021
- journal article
- research article
- Published by American Society of Clinical Oncology (ASCO) in Journal of Clinical Oncology
- Vol. 39 (7), 768-778
- https://doi.org/10.1200/jco.20.02308
Abstract
Reduced-intensity conditioning (RIC) regimens have extended the curative potential of allogeneic stem-cell transplantation to older adults with high-risk acute myeloid leukemia (AML) and myelodysplasia (MDS) but are associated with a high risk of disease relapse. Strategies to reduce recurrence are urgently required. Registry data have demonstrated improved outcomes using a sequential transplant regimen, fludarabine/amsacrine/cytarabine-busulphan (FLAMSA-Bu), but the impact of this intensified conditioning regimen has not been studied in randomized trials. Two hundred forty-four patients (median age, 59 years) with high-risk AML (n = 164) or MDS (n = 80) were randomly assigned 1:1 to a fludarabine-based RIC regimen or FLAMSA-Bu. Pretransplant measurable residual disease (MRD) was monitored by flow cytometry (MFC-MRD) and correlated with outcome. There was no difference in 2-year overall survival (hazard ratio 1.05 [85% CI, 0.80 to 1.38] P = .81) or cumulative incidence of relapse (CIR) (hazard ratio 0.94 [95%CI, 0.60 to 1.46] P = .81) between the control and FLAMSA-Bu arms. Detectable pretransplant MFC-MRD was associated with an increased CIR (2-year CIR 41.0% v 20.0%, P = .01) in the overall trial cohort with a comparable prognostic impact when measured by an unsupervised analysis approach. There was no evidence of interaction between MRD status and conditioning regimen intensity for relapse or survival. Acquisition of full donor T-cell chimerism at 3 months abrogated the adverse impact of pretransplant MRD on CIR and overall survival. The intensified RIC conditioning regimen, FLAMSA-Bu, did not improve outcomes in adults transplanted for high-risk AML or MDS regardless of pretransplant MRD status. Our data instead support the exploration of interventions with the ability to accelerate acquisition of full donor T-cell chimerism as a tractable strategy to improve outcomes in patients allografted for AML.Keywords
This publication has 38 references indexed in Scilit:
- Is there an optimal conditioning for older patients with AML receiving allogeneic hematopoietic cell transplantation?Blood, 2020
- Treosulfan or busulfan plus fludarabine as conditioning treatment before allogeneic haemopoietic stem cell transplantation for older patients with acute myeloid leukaemia or myelodysplastic syndrome (MC-FludT.14/L): a randomised, non-inferiority, phase 3 trialThe Lancet Haematology, 2019
- Measurable Residual Disease at Induction Redefines Partial Response in Acute Myeloid Leukemia and Stratifies Outcomes in Patients at Standard Risk Without NPM1 MutationsJournal of Clinical Oncology, 2018
- Conditioning regimens for allogeneic hematopoietic stem cell transplants in acute myeloid leukemiaBone Marrow Transplantation, 2017
- Myeloablative Versus Reduced-Intensity Hematopoietic Cell Transplantation for Acute Myeloid Leukemia and Myelodysplastic SyndromesJournal of Clinical Oncology, 2017
- Sequential Intensified Conditioning Regimen Allogeneic Hematopoietic Stem Cell Transplantation in Adult Patients with Intermediate- or High-Risk Acute Myeloid Leukemia in Complete Remission: A Study from the Acute Leukemia Working Party of the European Group for Blood and Marrow TransplantationTransplantation and Cellular Therapy, 2016
- High Prognostic Impact of Flow Cytometric Minimal Residual Disease Detection in Acute Myeloid Leukemia: Data From the HOVON/SAKK AML 42A StudyJournal of Clinical Oncology, 2013
- Toward Optimization of Postremission Therapy for Residual Disease–Positive Patients With Acute Myeloid LeukemiaJournal of Clinical Oncology, 2008
- Long-term survival in refractory acute myeloid leukemia after sequential treatment with chemotherapy and reduced-intensity conditioning for allogeneic stem cell transplantationBlood, 2006
- Sequential Regimen of Chemotherapy, Reduced-Intensity Conditioning for Allogeneic Stem-Cell Transplantation, and Prophylactic Donor Lymphocyte Transfusion in High-Risk Acute Myeloid Leukemia and Myelodysplastic SyndromeJournal of Clinical Oncology, 2005