Allogeneic Transplantation to Treat Therapy-Related Myelodysplastic Syndrome and Acute Myelogenous Leukemia in Adults

Leland Metheny, Natalie S. Callander, Aric C. Hall, Mei Jei Zhang, Khalid Bo-Subait, Hai Lin Wang, Vaibhav Agrawal, A. Samer Al-Homsi, Amer Assal, Ulrike Bacher, Amer Beitinjaneh, Nelli Bejanyan, Vijaya Raj Bhatt, Chris Bredeson, Michael Byrne, Mitchell Cairo, Jan Cerny, Zachariah DeFilipp, Miguel Angel Diaz Perez, César O. FreytesSiddhartha Ganguly, Michael R. Grunwald, Shahrukh Hashmi, Gerhard C. Hildebrandt, Yoshihiro Inamoto, Christopher G. Kanakry, Mohamed A. Kharfan-Dabaja, Hillard M. Lazarus, Jong Wook Lee, Sunita Nathan, Taiga Nishihori, Richard F. Olsson, Olov Ringdén, David Rizzieri, Bipin N. Savani, Mary Lynn Savoie, Sachiko Seo, Marjolein van der Poel, Leo F. Verdonck, John L. Wagner, Jean A. Yared, Christopher S. Hourigan, Partow Kebriaei, Mark Litzow, Brenda M. Sandmaier, Wael Saber, Daniel Weisdorf, Marcos de Lima

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Patients who develop therapy-related myeloid neoplasm, either myelodysplastic syndrome (t-MDS) or acute myelogenous leukemia (t-AML), have a poor prognosis. An earlier Center for International Blood and Marrow Transplant Research (CIBMTR) analysis of 868 allogeneic hematopoietic cell transplantations (allo-HCTs) performed between 1990 and 2004 showed a 5-year overall survival (OS) and disease-free survival (DFS) of 22% and 21%, respectively. Modern supportive care, graft-versus-host disease prophylaxis, and reduced-intensity conditioning (RIC) regimens have led to improved outcomes. Therefore, the CIBMTR analyzed 1531 allo-HCTs performed in adults with t-MDS (n = 759) or t-AML (n = 772) between and 2000 and 2014. The median age was 59 years (range, 18 to 74 years) for the patients with t-MDS and 52 years (range, 18 to 77 years) for those with t-AML. Twenty-four percent of patients with t-MDS and 11% of those with t-AML had undergone a previous autologous (auto-) HCT. A myeloablative conditioning (MAC) regimen was used in 49% of patients with t-MDS and 61% of patients with t-AML. Nonrelapse mortality at 5 years was 34% (95% confidence interval [CI], 30% to 37%) for patients with t-MDS and 34% (95% CI, 30% to 37%) for those with t-AML. Relapse rates at 5 years in the 2 groups were 46% (95% CI, 43% to 50%) and 43% (95% CI, 40% to 47%). Five-year OS and DFS were 27% (95% CI, 23% to 31%) and 19% (95% CI, 16% to 23%), respectively, for patients with t-MDS and 25% (95% CI, 22% to 28%) and 23% (95% CI, 20% to 26%), respectively, for those with t-AML. In multivariate analysis, OS and DFS were significantly better in young patients with low-risk t-MDS and those with t-AML undergoing HCT with MAC while in first complete remission, but worse for those with previous auto-HCT, higher-risk cytogenetics or Revised International Prognostic Scoring System score, and a partially matched unrelated donor. Relapse remains the major cause of treatment failure, with little improvement seen over the past 2 decades. These data mandate caution when recommending allo-HCT in these conditions and indicate the need for more effective antineoplastic approaches before and after allo-HCT.

Original languageEnglish
Pages (from-to)923.e1-923.e12
JournalTransplantation and Cellular Therapy
Volume27
Issue number11
DOIs
StatePublished - Nov 2021

Bibliographical note

Funding Information:
The CIBMTR is supported primarily by Public Health Service grant/cooperative agreement U24CA076518 with the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID); grant/cooperative agreement U24HL138660 with the NHLBI and NCI; grant R21 HL140314, and U01HL128568 from the NHLBI; contract HHSH250201700006C with the Health Resources and Services Administration (HRSA); grants N00014-18-1-2888 and N00014-17-1-2850 from the Office of Naval Research; subaward from prime contract award SC1MC31881-01-00 with the HRSA; subawards from prime grant awards R01 HL131731 and R01 HL126589 from the NHLBI; subawards from prime grant awards 5P01CA111412, 5R01HL129472, R01CA152108, 1R01HL131731, 1U01AI126612, and 1R01CA231141 from the NIH; and commercial funds from Actinium Pharmaceuticals, Adaptive Biotechnologies, Allovir, Amgen, anonymous donation to the Medical College of Wisconsin, Anthem, Astellas Pharma US, Atara Biotherapeutics, BARDA, Be the Match Foundation, bluebird bio, Boston Children's Hospital, Bristol Myers Squibb, Celgene, Children's Hospital of Los Angeles, Chimerix, City of Hope Medical Center, CSL Behring, CytoSen Therapeutics, Daiichi Sankyo, Dana Farber Cancer Institute, Enterprise Science and Computing, Fred Hutchinson Cancer Research Center, Gamida-Cell, Genzyme, Gilead Sciences, GlaxoSmithKline, HistoGenetics, Immucor, Incyte, Janssen Biotech, Janssen Pharmaceuticals, Janssen Research & Development, Janssen Scientific Affairs, Japan Hematopoietic Cell Transplantation Data Center, Jazz Pharmaceuticals, Karius, Karyopharm Therapeutics, Kite Pharma, Kyowa Kirin, Magenta Therapeutics, Mayo Clinic and Foundation Rochester, Medac, Mediware, Memorial Sloan Kettering Cancer Center, Merck & Company, Mesoblast, MesoScale Diagnostics, Millennium, Miltenyi Biotec, Mundipharma EDO, National Marrow Donor Program, Novartis Oncology, Novartis Pharmaceuticals, Omeros, Oncoimmune, OptumHealth, Orca Biosystems, PCORI, Pfizer, Phamacyclics, PIRCHE AG, Regeneron Pharmaceuticals, REGiMMUNE, Sanofi Genzyme, Seattle Genetics, Shire, Sobi, Spectrum Pharmaceuticals, St. Baldrick's Foundation, Swedish Orphan Biovitrum, Takeda Oncology, Medical College of Wisconsin, University of Minnesota, University of Pittsburgh, University of Texas-MD Anderson, University of Wisconsin-Madison, Viracor Eurofins, and Xenikos. The views expressed in this article do not reflect the official policy or position of the NIH, Department of the Navy, Department of Defense, the HRSA, or any other agency of the US Government.

Funding Information:
The CIBMTR is supported primarily by Public Health Service grant/cooperative agreement U24CA076518 with the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID); grant/cooperative agreement U24HL138660 with the NHLBI and NCI; grant R21 HL140314, and U01HL128568 from the NHLBI; contract HHSH250201700006C with the Health Resources and Services Administration (HRSA); grants N00014-18-1-2888 and N00014-17-1-2850 from the Office of Naval Research; subaward from prime contract award SC1MC31881-01-00 with the HRSA; subawards from prime grant awards R01 HL131731 and R01 HL126589 from the NHLBI; subawards from prime grant awards 5P01CA111412, 5R01HL129472, R01CA152108, 1R01HL131731, 1U01AI126612, and 1R01CA231141 from the NIH; and commercial funds from Actinium Pharmaceuticals, Adaptive Biotechnologies, Allovir, Amgen, anonymous donation to the Medical College of Wisconsin, Anthem, Astellas Pharma US, Atara Biotherapeutics, BARDA, Be the Match Foundation, bluebird bio, Boston Children's Hospital, Bristol Myers Squibb, Celgene, Children's Hospital of Los Angeles, Chimerix, City of Hope Medical Center, CSL Behring, CytoSen Therapeutics, Daiichi Sankyo, Dana Farber Cancer Institute, Enterprise Science and Computing, Fred Hutchinson Cancer Research Center, Gamida-Cell, Genzyme, Gilead Sciences, GlaxoSmithKline, HistoGenetics, Immucor, Incyte, Janssen Biotech, Janssen Pharmaceuticals, Janssen Research & Development, Janssen Scientific Affairs, Japan Hematopoietic Cell Transplantation Data Center, Jazz Pharmaceuticals, Karius, Karyopharm Therapeutics, Kite Pharma, Kyowa Kirin, Magenta Therapeutics, Mayo Clinic and Foundation Rochester, Medac, Mediware, Memorial Sloan Kettering Cancer Center, Merck & Company, Mesoblast, MesoScale Diagnostics, Millennium, Miltenyi Biotec, Mundipharma EDO, National Marrow Donor Program, Novartis Oncology, Novartis Pharmaceuticals, Omeros, Oncoimmune, OptumHealth, Orca Biosystems, PCORI, Pfizer, Phamacyclics, PIRCHE AG, Regeneron Pharmaceuticals, REGiMMUNE, Sanofi Genzyme, Seattle Genetics, Shire, Sobi, Spectrum Pharmaceuticals, St. Baldrick's Foundation, Swedish Orphan Biovitrum, Takeda Oncology, Medical College of Wisconsin, University of Minnesota, University of Pittsburgh, University of Texas-MD Anderson, University of Wisconsin-Madison, Viracor Eurofins, and Xenikos. The views expressed in this article do not reflect the official policy or position of the NIH, Department of the Navy, Department of Defense, the HRSA, or any other agency of the US Government. Financial disclosure: There are no financial relationships to disclose. Conflict of interest statement: There are no conflicts of interest to disclose.

Publisher Copyright:
© 2021

Keywords

  • Acute myelogenous leukemia
  • Allogeneic transplantation
  • Myelodysplasia

ASJC Scopus subject areas

  • Immunology and Allergy
  • Molecular Medicine
  • Hematology
  • Cell Biology
  • Transplantation

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