Comparison of outcomes of HCT in blast phase of BCR-ABL12 MPN with de novo AML and with AML following MDS

Vikas Gupta, Soyoung Kim, Zhen Huan Hu, Ying Liu, Mahmoud Aljurf, Ulrike Bacher, Amer Beitinjaneh, Jean Yves Cahn, Jan Cerny, Edward Copelan, Shahinaz M. Gadalla, Robert Peter Gale, Siddhartha Ganguly, Biju George, Aaron T. Gerds, Usama Gergis, Betty K. Hamilton, Shahrukh Hashmi, Gerhard C. Hildebrandt, Rammurti T. KambleTamila Kindwall-Keller, Hillard M. Lazarus, Jane L. Liesveld, Mark Litzow, Richard T. Maziarz, Taiga Nishihori, Richard F. Olsson, David Rizzieri, Bipin N. Savani, Sachiko Seo, Melhem Solh, Jeff Szer, Leo F. Verdonck, Baldeep Wirk, Ann Woolfrey, Jean A. Yared, Edwin P. Alyea, Uday R. Popat, Ronald M. Sobecks, Bart L. Scott, Ryotaro Nakamura, Wael Saber

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Comparative outcomes of allogeneic hematopoietic cell transplantation (HCT) for BCR-ABL12 myeloproliferative neoplasms (MPNs) in blast phase (MPN-BP) vs de novo acute myeloid leukemia (AML), and AML with prior myelodysplastic syndromes (MDSs; post-MDS AML), are unknown. Using the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we compared HCT outcomes in 177 MPN-BP patients with 4749 patients with de novo AML, and 1104 patients with post-MDS AML, using multivariate regression analysis in 2 separate comparisons. In a multivariate Cox model, no difference in overall survival (OS) or relapse was observed in patients with MPN-BP vs de novo AML with active leukemia at HCT. Patients with MPN-BP in remission had inferior OS in comparison with de novo AML in remission (hazard ratio [HR], 1.40 [95% confidence interval [CI], 1.12-1.76]) due to higher relapse rate (HR, 2.18 [95% CI, 1.69-2.80]). MPN-BP patients had inferior OS (HR, 1.19 [95% CI, 1.00-1.43]) and increased relapse (HR, 1.60 [95% CI, 1.31-1.96]) compared with post-MDS AML. Poor-risk cytogenetics were associated with increased relapse in both comparisons. Peripheral blood grafts were associated with decreased relapse in MPN-BP and post-MDS AML (HR, 0.70 [95% CI, 0.57-0.86]). Nonrelapse mortality (NRM) was similar between MPN-BP vs de novo AML, and MPN-BP vs post-MDS AML. Total-body irradiation-based myeloablative conditioning was associated with higher NRM in both comparisons. Survival of MPN-BP after HCT is inferior to de novo AML in remission and post-MDS AML due to increased relapse. Relapse-prevention strategies are required to optimize HCT outcomes in MPN-BP.

Original languageEnglish
Pages (from-to)4748-4757
Number of pages10
JournalBlood advances
Volume4
Issue number19
DOIs
StatePublished - Oct 13 2020

Bibliographical note

Funding Information:
Acknowledgments The CIBMTR was supported primarily by Public Health Service U24CA076518 from the National Cancer Institute, the National Heart, Lung, and Blood Institute, and the National Institute of Allergy and Infectious Diseases of the National Institutes of Health; U24HL138660 from the National Heart, Lung, and Blood Institute and National Cancer Institute; T3HL147741, R21HL140314, and U01HL128568 from the National Heart, Lung, and Blood Institute; HHSH250201700006C, SC1MC31881-01-00, and HHSH250201700007C from the Health Resources and Services Administration; and N00014-18-1-2850, N00014-18-1-2888, and N00014-20-1-2705 from the Office of Naval Research. Additional federal support was provided by P01CA111412, R01CA152108, R01CA215134, R01CA218285, and R01CA231141 from the National Cancer Institute; R01HL126589 from the National Heart, Lung, and Blood Institute; R01AI128775 from the National Institute of Allergy and Infectious Diseases; R01HL129472, R01HL130388, and R01HL131731 from the National Heart, Lung, and Blood Institute; U01AI069197 and U01AI126612 from the National Institute of Allergy and Infectious Diseases; and Biomedical Advanced Research and Development Authority. Support was also provided by Be the Match Foundation, Boston Children’s Hospital, Dana-Farber, Japan Hematopoietic Cell Transplantation Data Center, St. Baldrick’s Foundation, the National Marrow Donor Program, the Medical College of Wisconsin, and from the following commercial entities: AbbVie; Actinium Pharmaceuticals, Inc; Adaptive Biotechnologies; Adienne SA; Allovir, Inc; Amgen, Inc; Anthem, Inc; Astellas Pharma US; AstraZeneca; Atara Biother-apeutics, Inc; bluebird bio, Inc; Bristol Myers Squibb; Celgene Corp; Chimerix, Inc; CSL Behring; CytoSen Therapeutics, Inc; Daiichi Sankyo Co Ltd; Gamida-Cell, Ltd; Genzyme; GlaxoSmithK-line (GSK); HistoGenetics, Inc; Incyte Corporation; Janssen Biotech, Inc; Janssen Pharmaceuticals, Inc; Janssen/Johnson & Johnson; Jazz Pharmaceuticals, Inc; Kiadis Pharma; Kite Pharma; Kyowa Kirin; Legend Biotech; Magenta Therapeutics; Mallinckrodt LLC; Medac GmbH; Merck & Company, Inc; Merck Sharp & Dohme Corp; Mesoblast; Millennium, the Takeda Oncology Co; Miltenyi Biotec, Inc; Novartis Oncology; Novartis Pharmaceuticals Corporation; Omeros Corporation; Oncoimmune, Inc; Orca Biosystems, Inc; Pfizer, Inc; Phamacyclics, LLC; Regeneron Pharmaceuticals, Inc; REGiMMUNE Corp; Sanofi Genzyme; Seattle Genetics; Sobi,

Funding Information:
The CIBMTR was supported primarily by Public Health Service U24CA076518 from the National Cancer Institute, the National Heart, Lung, and Blood Institute, and the National Institute of Allergy and Infectious Diseases of the National Institutes of Health; U24HL138660 from the National Heart, Lung, and Blood Institute and National Cancer Institute; T3HL147741, R21HL140314, and U01HL128568 from the National Heart, Lung, and Blood Institute; HHSH250201700006C, SC1MC31881-01-00, and HHSH250201700007C from the Health Resources and Services Administration; and N00014-18-1-2850, N00014-18-1-2888, and N00014-20-1-2705 from the Office of Naval Research. Additional federal support was provided by P01CA111412, R01CA152108, R01CA215134, R01CA218285, and R01CA231141 from the National Cancer Institute; R01HL126589 from the National Heart, Lung, and Blood Institute; R01AI128775 from the National Institute of Allergy and Infectious Diseases; R01HL129472, R01HL130388, and R01HL131731 from the National Heart, Lung, and Blood Institute; U01AI069197 and U01AI126612 from the National Institute of Allergy and Infectious Diseases; and Biomedical Advanced Research and Development Authority. Support was also provided by Be the Match Foundation, Boston Children's Hospital, Dana-Farber, Japan Hematopoietic Cell Transplantation Data Center, St. Baldrick's Foundation, the National Marrow Donor Program, the Medical College of Wisconsin, and from the following commercial entities: AbbVie; Actinium Pharmaceuticals, Inc; Adaptive Biotechnologies; Adienne SA; Allovir, Inc; Amgen, Inc; Anthem, Inc; Astellas Pharma US; AstraZeneca; Atara Biotherapeutics, Inc; bluebird bio, Inc; Bristol Myers Squibb; Celgene Corp; Chimerix, Inc; CSL Behring; CytoSen Therapeutics, Inc; Daiichi Sankyo Co Ltd; Gamida-Cell, Ltd; Genzyme; GlaxoSmithKline (GSK); HistoGenetics, Inc; Incyte Corporation; Janssen Biotech, Inc; Janssen Pharmaceuticals, Inc; Janssen/Johnson & Johnson; Jazz Pharmaceuticals, Inc; Kiadis Pharma; Kite Pharma; Kyowa Kirin; Legend Biotech; Magenta Therapeutics; Mallinckrodt LLC; Medac GmbH; Merck & Company, Inc; Merck Sharp & Dohme Corp; Mesoblast; Millennium, the Takeda Oncology Co; Miltenyi Biotec, Inc; Novartis Oncology; Novartis Pharmaceuticals Corporation; Omeros Corporation; Oncoimmune, Inc; Orca Biosystems, Inc; Pfizer, Inc; Phamacyclics, LLC; Regeneron Pharmaceuticals, Inc; REGiMMUNE Corp; Sanofi Genzyme; Seattle Genetics; Sobi, Inc; Takeda Oncology; Takeda Pharma; Terumo BCT; Viracor Eurofins; and Xenikos BV. The views expressed in this article do not reflect the official policy or position of the National Institutes of Health, the Department of the Navy, the Department of Defense, the Health Resources and Services Administration, or any other agency of the US government.

Funding Information:
Conflict-of-interest disclosure: V.G. provided consultancy services to Novartis and Celgene; received research funding from Novartis and Incyte; and was on advisory boards for Novartis, Cel-gene, and Sierra Oncology. R.M.S. was on an advisory board for CareDx. B.L.S. held advisory roles with Celgene, Alexion, Novartis, and Incyte. R.N. reports grants from Miyarisan and Helocyte, and personal fees from Celgene, Merck, and Kyowa-Kirin, from null, outside of the submitted work. G.C.H. reports participating on an advisory board for Incyte; receiving research funding from Phama-cyclics, Takeda, Jazz Pharmaceuticals, Incyte, and Astellas Pharma; and receiving travel, accommodations, and expenses from Incyte, The Falk Foundation, and Takeda. The remaining authors declare no competing financial interests.

Publisher Copyright:
© 2020 American Society of Hematology. All rights reserved.

ASJC Scopus subject areas

  • Hematology

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