Myeloablative versus Reduced-Intensity Conditioning for Hematopoietic Cell Transplantation in Acute Myelogenous Leukemia and Myelodysplastic Syndromes—Long-Term Follow-Up of the BMT CTN 0901 Clinical Trial: B. Scott et al

Bart L. Scott, Marcelo C. Pasquini, Mingwei Fei, Raphael Fraser, Juan Wu, Steve M. Devine, David L. Porter, Richard T. Maziarz, Erica Warlick, Hugo F. Fernandez, Robert J. Soiffer, Edwin Alyea, Mehdi Hamadani, Asad Bashey, Sergio Giralt, Nancy L. Geller, Eric Leifer, Christopher S. Hourigan, Gege Gui, Adam MendizabalMary M. Horowitz, H. Joachim Deeg, Mitchell E. Horwitz

Research output: Contribution to journalArticlepeer-review

Abstract

Several prospective randomized trials comparing conditioning intensity before allogeneic hematopoietic cell transplantation (HCT) have been performed, with conflicting results. Although reduced-intensity conditioning (RIC) leads to lower treatment-related mortality (TRM), this is offset by higher rates of relapse. Long-term follow-up of randomized comparative trials are limited. Here we present long-term follow-up of a randomized comparison of myeloablative conditioning (MAC) compared with RIC before HCT for acute myelogenous leukemia (AML) or myelodysplasia (MDS). Long-term comparative analyses of overall survival, relapse, and relapse-free survival were performed. Patients age 18 to 65 years with <5% marrow myeloblasts were randomized to receive MAC (n = 135) or RIC (n = 137), followed by HCT from an HLA-matched donor. The primary endpoint of the trial was an 18-month pointwise comparison of overall survival. The analyses were performed using a proportional hazards model. The median follow-up of the entire cohort was 51 months. At 4 years, the transplant-related mortality (TRM) was 25.1% for MAC, compared with 9.9% for RIC (P < .001). Patients who received RIC had a significantly higher risk of relapse compared to those who received MAC (hazard ratio [HR], 4.06; 95% CI, 2.59 to 6.35; P < 0.001). Among the patients who relapsed after HCT, postrelapse survival was similar at 3 years (24% for MAC and 26% for RIC). Overall survival was superior for patients who received MAC compared to those who received RIC (HR, 1.54; 95% CI, 1.07 to 2.2; P = .03). Our data show that patients who received MAC were at higher risk of late TRM compared with those who received RIC; however, because of the exceedingly high rates of relapse in the RIC arm, overall survival remained significantly better for patients who received MAC. Among patients with MDS or AML eligible for either MAC or RIC regimens, long-term follow up demonstrates a survival advantage for patients who received MAC.

Original languageEnglish (US)
Pages (from-to)483.e1-483.e6
JournalTransplantation and Cellular Therapy
Volume27
Issue number6
DOIs
StatePublished - Jun 2021

Bibliographical note

Funding Information:
Financial disclosure: Support for this study was provided by grants U10HL069294 and U24HL138660 to the BMT CTN from the National Heart, Lung and Blood Institutes and the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The CIBMTR registry is supported primarily by the U24-CA76518 from the National Cancer Institute, the National Heart, Lung and Blood Institute, and the National Institute of Allergy and Infectious Diseases and from Grant HHSH234200637015C (Health Resources and Services Administration/Department of Health and Human Services) to the CIBMTR. The 32 transplant centers (with principal investigator) that enrolled patients into this trial under the auspices of the BMT CTN (Protocol 0901) are as follows: Baylor University Medical Center (Edward Agura); Blood and Marrow Transplant Program at Northside Hospital (Lawrence E. Morris); Cleveland Clinic Foundation (Ronald Sobecks); Dana-Farber Cancer Institute/Brigham & Women's (Edwin Alyea); Duke University Medical Center (Mitch Horwitz); Emory University (Amelia Langston); Florida Hospital Cancer Institute (Shahram Mori); Fred Hutchinson Cancer Research Center (Bart Scott); H. Lee Moffitt Cancer Center (Hugo Fernandez); Jewish Hospital BMT Program (Ed Faber); Karmanos Cancer Institute (Joseph Uberti); Mayo Clinic–Phoenix (Mark Litzow); Mayo Clinic–Rochester (James Slack); Medical College of Wisconsin (Marcelo Pasquini); Mount Sinai Medical Center (Adriana Malone); Oregon Health & Science University (Gabrielle Meyers); Roswell Park Cancer Institute (Maureen Ross); Texas Transplant Institute (Carlos Bachier; changed to Seema Naik on 3/21/2014); UCSD Medical Center (Edward Ball); University Hospitals of Cleveland/ Case Western (Hillard Lazarus); University of Florida College of Medicine (Shands) (John Wingard); University of Kansas Hospital (Sunil Abhyankar); University of Kentucky (Zartash Gul; changed to Gerhard Hildebrandt on 3/1/2016); University of Minnesota (Erica Warlick); University of Nebraska Medical Center (Lori Maness-Harris); University of North Carolina Hospital at Chapel Hill (Thomas Shea); University of Pennsylvania Cancer Center (David L. Porter); University of Rochester Medical Center (Michael Becker); University of Wisconsin Hospital and Clinics (Mark B. Juckett); Utah BMT/University of Utah Medical School (Michael Boyer); Washington University/Barnes Jewish Hospital (Peter Westervelt); West Virginia University Hospital (Michael Craig).

Funding Information:
We thank the members of the BMT CTN, the research nurses, and the patients who participated in this trial. Financial disclosure: Support for this study was provided by grants U10HL069294 and U24HL138660 to the BMT CTN from the National Heart, Lung and Blood Institutes and the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The CIBMTR registry is supported primarily by the U24-CA76518 from the National Cancer Institute, the National Heart, Lung and Blood Institute, and the National Institute of Allergy and Infectious Diseases and from Grant HHSH234200637015C (Health Resources and Services Administration/Department of Health and Human Services) to the CIBMTR. The 32 transplant centers (with principal investigator) that enrolled patients into this trial under the auspices of the BMT CTN (Protocol 0901) are as follows: Baylor University Medical Center (Edward Agura); Blood and Marrow Transplant Program at Northside Hospital (Lawrence E. Morris); Cleveland Clinic Foundation (Ronald Sobecks); Dana-Farber Cancer Institute/Brigham & Women's (Edwin Alyea); Duke University Medical Center (Mitch Horwitz); Emory University (Amelia Langston); Florida Hospital Cancer Institute (Shahram Mori); Fred Hutchinson Cancer Research Center (Bart Scott); H. Lee Moffitt Cancer Center (Hugo Fernandez); Jewish Hospital BMT Program (Ed Faber); Karmanos Cancer Institute (Joseph Uberti); Mayo Clinic?Phoenix (Mark Litzow); Mayo Clinic?Rochester (James Slack); Medical College of Wisconsin (Marcelo Pasquini); Mount Sinai Medical Center (Adriana Malone); Oregon Health & Science University (Gabrielle Meyers); Roswell Park Cancer Institute (Maureen Ross); Texas Transplant Institute (Carlos Bachier; changed to Seema Naik on 3/21/2014); UCSD Medical Center (Edward Ball); University Hospitals of Cleveland/ Case Western (Hillard Lazarus); University of Florida College of Medicine (Shands) (John Wingard); University of Kansas Hospital (Sunil Abhyankar); University of Kentucky (Zartash Gul; changed to Gerhard Hildebrandt on 3/1/2016); University of Minnesota (Erica Warlick); University of Nebraska Medical Center (Lori Maness-Harris); University of North Carolina Hospital at Chapel Hill (Thomas Shea); University of Pennsylvania Cancer Center (David L. Porter); University of Rochester Medical Center (Michael Becker); University of Wisconsin Hospital and Clinics (Mark B. Juckett); Utah BMT/University of Utah Medical School (Michael Boyer); Washington University/Barnes Jewish Hospital (Peter Westervelt); West Virginia University Hospital (Michael Craig). Conflict of interest statement: There are no conflicts of interest to report. Financial disclosure: See Acknowledgments on page 487.

Publisher Copyright:
© 2021

Keywords

  • Acute myelogenous leukemia
  • Conditioning intensity
  • Hematopoietic cell transplantation
  • Myelodysplastic syndrome

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