Abstract

The preferred post-remission therapy for older patients with acute myeloid leukemia (AML) in first complete remission (CR1) remains uncertain. In this retrospective, multicenter study, we compared the outcomes for older AML patients (age 60–77 years) receiving allogeneic hematopoietic cell transplantation (alloHCT) (n = 431) with those treated on prospective National Clinical Trials Network induction and nontransplantation chemotherapy (CT) consolidation trials (n = 211). AlloHCT patients were younger (median age: 64.2 versus 67.9 years, p < 0.001), but more frequently had high-risk AML (high WBC, secondary AML, and unfavorable cytogenetics). Overall survival (OS) was worse in alloHCT during the first 9 months after CR1 (HR = 1.52, p = 0.02), but was significantly better thereafter (HR = 0.53, p < 0.0001) relative to CT. Treatment-related mortality (TRM) following HCT was worse in the first 9 months (HR = 2.8, 95% CI: 1.5–5.2, p = 0.0009), while post-HCT relapse was significantly less frequent beyond 9 months (HR = 0.42, 95% CI: 0.29–0.61, p < 0.0001). Despite higher early TRM, alloHCT recipients had superior long-term OS [29% (24–34%) versus CT 13.8% (9–21%) at 5 years]. Although this is a retrospective analysis with potential biases, it indicates that alloHCT led to heightened early risks from TRM, yet reduced relapse and superior long-term survival relative to CT in older AML patients in CR1.

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Acknowledgements

We express our deepest appreciation to the late A H who contributed to this work from inception to the first draft of the paper. We are forever indebted to her efforts. Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under the award number UG1CA189823 to the Alliance for Clinical Trials in Oncology NCORP Research Base (Jan C. Buckner, M.D., contact PI). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Other grant award numbers are as follows: U10CA180819, CA180820, CA180794, CA180790, and CA180791.

Author contributions

CU and AA conceived the idea, searched literature, analyzed the data, wrote and edited the manuscript. JLR, BM, ES, HLW, MJZ, and DJW collected data, analyzed data, wrote and edited the manuscript. RS, RAL, AH, TCS, MDL, AJW, HPE, MST, FA, CDB, MO, JML, SC, GM, KM, BS, ECA, ML, and ZS helped data collection, wrote and edited the manuscript. SN, GJR, GLU, JMF, LDC, and AJ were the principal investigators of the relevant cooperative group studies, and wrote and edited the manuscript.

Author information

Affiliations

  1. Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, MN, USA

    • Celalettin Ustun
    •  & Daniel J. Weisdorf
  2. Division of Hematology, Oncology and Cellular Therapy, Rush University, Chicago, IL, USA

    • Celalettin Ustun
  3. Department of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA

    • Jennifer Le-Rademacher
  4. CIBMTR (Center for International Blood and Marrow Transplant Research), Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA

    • Hai-Lin Wang
    • , Mei-Jie Zhang
    •  & Daniel J. Weisdorf
  5. Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    • Megan Othus
  6. Harvard T.H. Chan School of Public Health, Boston, MA, USA

    • Zhuoxin Sun
  7. Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA

    • Brittny Major
  8. Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN, USA

    • Elizabeth Storrick
  9. Mayo Clinic, Rochester, MN, USA

    • Jacqueline M. Lafky
    •  & Aminah Jatoi
  10. University of Chicago Comprehensive Cancer Center, Chicago, IL, USA

    • Selina Chow
  11. The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA

    • Krzysztof Mrózek
  12. Massachusetts General Hospital, Boston, MA, USA

    • Eyal C. Attar
  13. Agios Pharmaceuticals, Inc, Cambridge, MA, USA

    • Eyal C. Attar
  14. Loyola University Medical Center, Chicago, IL, USA

    • Such Nand
  15. Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA

    • Clara D. Bloomfield
  16. Indiana University Simon Cancer Center, Indianapolis, IN, USA

    • Larry D. Cripe
  17. Memorial Sloan Kettering Cancer Center, New York, NY, USA

    • Martin S. Tallman
  18. Fred Hutchinson Cancer Research Center and Division of Oncology, University of Washington, Seattle, WA, USA

    • Frederick Appelbaum
    •  & Brenda M. Sandmaier
  19. Department of Medicine and Comprehensive Cancer Center, University of Chicago, Chicago, IL, USA

    • Richard A. Larson
    •  & Andrew S. Artz
  20. Department of Hematological Malignancies Translational Science, Gehr Family Center for Leukemia Research, Hematologic Malignancies and Stem Cell Transplantation Institute, Beckman Research Institute, City of Hope, Duarte, CA, USA

    • Guido Marcucci
  21. Weill-Cornell Medical College, New York, NY, USA

    • Gail J. Roboz
  22. Washington University School of Medicine, Saint Louis, MO, USA

    • Geoffrey L. Uy
  23. Dana-Farber Cancer Institute, Boston, MA, USA

    • Richard M. Stone
  24. Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA

    • Thomas C. Shea
  25. Adult Hematologic Malignancies & Stem Cell Transplant Section, University Hospitals Seidman Cancer Center, Cleveland, OH, USA

    • Marcos de Lima
  26. Division of Hematology and Medical Oncology, Department of Medicine, Mayo Clinic Florida, Jacksonville, FL, USA

    • James M. Foran
  27. Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA

    • Mark R. Litzow
  28. Duke University, Durham, NC, USA

    • Harry P. Erba
  29. City of Hope, Duarte, CA, USA

    • Arti Hurria

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Correspondence to Celalettin Ustun.

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https://doi.org/10.1038/s41375-019-0477-x