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Conditioning Intensity, Pre-Transplant Flow Cytometric Measurable Residual Disease, and Outcome in Adults with Acute Myeloid Leukemia Undergoing Allogeneic Hematopoietic Cell Transplantation

Authors
  • Morsink, Linde M.1, 2
  • Sandmaier, Brenda M.1, 3
  • Othus, Megan
  • Palmieri, Raffaele1
  • Granot, Noa1
  • Bezerra, Evandro D.
  • Wood, Brent L.
  • Mielcarek, Marco1, 3
  • Schoch, Gary1
  • Davis, Chris1
  • Flowers, Mary E. D.1, 3
  • Deeg, H. Joachim1, 3
  • Appelbaum, Frederick R.1, 3
  • Storb, Rainer1, 3
  • Walter, Roland B.1, 4, 5
  • 1 (R.S.)
  • 2 Department of Hematology, University Medical Center Groningen, 9700 RB Groningen, The Netherlands
  • 3 Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, WA 98195, USA
  • 4 Division of Hematology, Department of Medicine, University of Washington, Seattle, WA 98195, USA
  • 5 Department of Epidemiology, University of Washington, Seattle, WA 98195, USA
Type
Published Article
Journal
Cancers
Publisher
MDPI AG
Publication Date
Aug 19, 2020
Volume
12
Issue
9
Identifiers
DOI: 10.3390/cancers12092339
PMID: 32825022
PMCID: PMC7565021
Source
PubMed Central
Keywords
License
Green

Abstract

How conditioning intensity is related to outcomes of AML patients undergoing allografting in morphologic remission is an area of great ongoing interest. We studied 743 patients in morphologic remission and known pre-transplant measurable residual disease (MRD) status determined by multiparameter flow cytometry (MFC) who received a first allograft after myeloablative, reduced intensity, or nonmyeloablative conditioning (MAC, RIC, and NMA). Overall, relapse-free survival (RFS) and overall survival (OS) were longer after MAC than RIC or NMA conditioning, whereas relapse risks were not different. Among MRDpos patients, 3-year estimates of relapse risks and survival were similar across conditioning intensities. In contrast, among MRDneg patients, 3-year RFS and OS were longer for MAC (69% and 71%) than RIC (47% and 55%) and NMA conditioning (47% and 52%). Three-year relapse risks were lowest after MAC (18%) and highest after NMA conditioning (30%). Our data indicate an interaction between conditioning intensity, MFC-based pre-transplant MRD status, and outcome, with benefit of intensive conditioning primarily for patients transplanted in MRDneg remission. Differing from recent findings from other studies that indicated MAC is primarily beneficial for some or all patients with MRDpos pre-HCT status, our data suggest MAC should still be considered for MRDneg AML patients if tolerated.

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