Hematopoietic Cell Transplantation Outcomes in Monosomal Karyotype Myeloid Malignancies

Marcelo C. Pasquini, Mei Jie Zhang, Bruno C. Medeiros, Philippe Armand, Zhen Huan Hu, Taiga Nishihori, Mahmoud D. Aljurf, Görgün Akpek, Jean Yves Cahn, Mitchell S. Cairo, Jan Cerny, Edward A. Copelan, Abhinav Deol, César O. Freytes, Robert Peter Gale, Siddhartha Ganguly, Biju George, Vikas Gupta, Gregory A. Hale, Rammurti T. KambleThomas R. Klumpp, Hillard M. Lazarus, Selina M. Luger, Jane L. Liesveld, Mark R. Litzow, David I. Marks, Rodrigo Martino, Maxim Norkin, Richard F. Olsson, Betul Oran, Attaphol Pawarode, Michael A. Pulsipher, Muthalagu Ramanathan, Ran Reshef, Ayman A. Saad, Wael Saber, Bipin N. Savani, Harry C. Schouten, Olle Ringdén, Martin S. Tallman, Geoffrey L. Uy, William A. Wood, Baldeep Wirk, Waleska S. Pérez, Minoo Batiwalla, Daniel J. Weisdorf

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

The presence of monosomal karyotype (MK+) in acute myeloid leukemia (AML) is associated with dismal outcomes. We evaluated the impact of MK+ in AML (MK+AML, n = 240) and in myelodysplastic syndrome (MDS) (MK+MDS, n = 221) on hematopoietic cell transplantation outcomes compared with other cytogenetically defined groups (AML, n = 3360; MDS, n = 1373) as reported to the Center for International Blood and Marrow Transplant Research from 1998 to 2011. MK+ AML was associated with higher disease relapse (hazard ratio, 1.98; P <.01), similar transplantation-related mortality (TRM) (hazard ratio, 1.01; P =90), and worse survival (hazard ratio, 1.67; P <.01) compared with those outcomes for other cytogenetically defined AML. Among patients with MDS, MK+ MDS was associated with higher disease relapse (hazard ratio, 2.39; P <.01), higher TRM (hazard ratio, 1.80; P <.01), and worse survival (HR, 2.02; P <.01). Subset analyses comparing chromosome 7 abnormalities (del7/7q) with or without MK+ demonstrated higher mortality for MK+ disease in for both AML (hazard ratio, 1.72; P <.01) and MDS (hazard ratio, 1.79; P <.01). The strong negative impact of MK+ in myeloid malignancies was observed in all age groups and using either myeloablative or reduced-intensity conditioning regimens. Alternative approaches to mitigate disease relapse in this population are needed.

Original languageEnglish (US)
Pages (from-to)248-257
Number of pages10
JournalBiology of Blood and Marrow Transplantation
Volume22
Issue number2
DOIs
StatePublished - Feb 1 2016

Bibliographical note

Funding Information:
Additional members from the Writing Committee who offered input different stages of development of this study include Camille N. Abboud, Bruce Camitta, William Drobyski, Sergio Giralt, Vincent Ho, Luis Isola, John Koreth, Mary Laughlin, Ian Lewis, Michael Lil, Selina Luger, Richard Maziarz, Ryan Mattinson, Joseph McGuirk Reinhold Munker, Amandee Salhorta, Salyka Sengsayadeth, Gerard Socié. The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement U24-CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID); a grant/cooperative agreement 5U10HL069294 from NHLBI and NCI; a contract HHSH250201200016C with Health Resources and Services Administration (HRSA/DHHS); 2 grants N00014-13-1-0039 and N00014-14-1-0028 from the Office of Naval Research; and grants from *Actinium Pharmaceuticals; Allos Therapeutics, Inc.; *Amgen, Inc.; anonymous donation to the Medical College of Wisconsin; Ariad; Be the Match Foundation; *Blue Cross and Blue Shield Association; *Celgene Corporation; Chimerix, Inc.; Fred Hutchinson Cancer Research Center; Fresenius-Biotech North America, Inc.; *Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.;*Gentium SpA; Genzyme Corporation; GlaxoSmithKline; Health Research, Inc. Roswell Park Cancer Institute; HistoGenetics, Inc.; Incyte Corporation; Jeff Gordon Children''s Foundation; Kiadis Pharma; The Leukemia & Lymphoma Society; Medac GmbH; The Medical College of Wisconsin; Merck & Co, Inc.; Millennium: The Takeda Oncology Co.; *Milliman USA, Inc.; *Miltenyi Biotec, Inc.; National Marrow Donor Program; Onyx Pharmaceuticals; Optum Healthcare Solutions, Inc.; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; Perkin Elmer, Inc.; *Remedy Informatics; *Sanofi US; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; St. Baldrick''s Foundation; StemCyte, A Global Cord Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan Biovitrum; *Tarix Pharmaceuticals; *TerumoBCT; *Teva Neuroscience, Inc.; *THERAKOS, Inc.; University of Minnesota; University of Utah; and *Wellpoint, Inc. The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the Department of the Navy, the Department of Defense, Health Resources and Services Administration (HRSA) or any other agency of the United States Government. Financial disclosure: There is nothing to disclose. Conflict of interest statement: There are no conflicts of interest to report.

Funding Information:
The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement U24-CA076518 from the National Cancer Institute (NCI) , the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID) ; a grant/cooperative agreement 5U10HL069294 from NHLBI and NCI; a contract HHSH250201200016C with Health Resources and Services Administration (HRSA/DHHS); 2 grants N00014-13-1-0039 and N00014-14-1-0028 from the Office of Naval Research ; and grants from *Actinium Pharmaceuticals; Allos Therapeutics, Inc.; *Amgen, Inc.; anonymous donation to the Medical College of Wisconsin; Ariad; Be the Match Foundation; *Blue Cross and Blue Shield Association; *Celgene Corporation; Chimerix, Inc.; Fred Hutchinson Cancer Research Center; Fresenius-Biotech North America, Inc.; *Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.;*Gentium SpA; Genzyme Corporation; GlaxoSmithKline; Health Research, Inc. Roswell Park Cancer Institute; HistoGenetics, Inc.; Incyte Corporation; Jeff Gordon Children's Foundation; Kiadis Pharma; The Leukemia & Lymphoma Society; Medac GmbH; The Medical College of Wisconsin; Merck & Co, Inc.; Millennium: The Takeda Oncology Co.; *Milliman USA, Inc.; *Miltenyi Biotec, Inc.; National Marrow Donor Program; Onyx Pharmaceuticals; Optum Healthcare Solutions, Inc.; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; Perkin Elmer, Inc.; *Remedy Informatics; *Sanofi US; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; St. Baldrick's Foundation; StemCyte, A Global Cord Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan Biovitrum; *Tarix Pharmaceuticals; *TerumoBCT; *Teva Neuroscience, Inc.; *THERAKOS, Inc.; University of Minnesota; University of Utah; and *Wellpoint, Inc. The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the Department of the Navy, the Department of Defense, Health Resources and Services Administration (HRSA) or any other agency of the United States Government.

Publisher Copyright:
© 2016 American Society for Blood and Marrow Transplantation.

Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.

Keywords

  • Acute myeloid leukemia
  • Allogeneic transplantation
  • Monosomal karyotype
  • Myelodysplastic syndrome

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