The Role of Donor Lymphocyte Infusion (DLI) in Post-Hematopoietic Cell Transplant (HCT) Relapse for Chronic Myeloid Leukemia (CML) in the Tyrosine Kinase Inhibitor (TKI) Era: Role of DLI in Post-HCT Relapse for CML in the TKI Era

Sarah Schmidt, Ying Liu, Zhen Huan Hu, Kirsten M. Williams, Hillard M. Lazarus, Ravi Vij, Mohamed A. Kharfan-Dabaja, Guillermo Ortí, Peter H. Wiernik, Daniel Weisdorf, Rammurti T. Kamble, Roger Herzig, Baldeep Wirk, Jan Cerny, Ulrike Bacher, Naeem A. Chaudhri, Sunita Nathan, Nosha Farhadfar, Mahmoud Aljurf, Usama GergisJeffrey Szer, Sachiko Seo, Jack W. Hsu, Richard F. Olsson, Dipnarine Maharaj, Biju George, Gerhard C. Hildebrandt, Vaibhav Agrawal, Taiga Nishihori, Hisham Abdel-Azim, Edwin Alyea, Uday Popat, Ronald Sobecks, Bart L. Scott, Jennifer Holter Chakrabarty, Wael Saber

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Treatment for relapse of chronic myeloid leukemia (CML) following hematopoietic cell transplantation (HCT) includes tyrosine kinase inhibitors (TKIs) with or without donor lymphocyte infusions (DLIs), but the most effective treatment strategy is unknown. This study was performed through the Center for International Blood and Marrow Transplant Research (CIBMTR) database. We retrospectively reviewed all patients reported to the CIBMTR registry from 2002 to 2014 who underwent HCT for CML and were alive 30 days postrelapse. A total of 215 HCT recipients relapsed and were analyzed in the following groups: (1) TKI alone (n = 128), (2) TKI with DLI (n = 48), and (3) DLI without TKI (n = 39). In multivariate analysis, disease status prior to HCT had a significant effect on overall survival (OS). Patients who received a DLI alone compared with a TKI with a DLI had inferior survival (hazard ratio, 2.28; 95% confidence interval, 1.23 to 4.24; P= .009). Those who received a TKI alone had similar survival compared with those who received a TKI with a DLI (P = .81). These data support that despite use of TKIs pretransplantation, TKI salvage therapy continues to provide significant survival following relapse in patients with CML following HCT. These data do not suggest that adding a DLI to a TKI adds an improvement in OS.

Original languageEnglish
Pages (from-to)1137-1143
Number of pages7
JournalBiology of Blood and Marrow Transplantation
Volume26
Issue number6
DOIs
StatePublished - Jun 2020

Bibliographical note

Publisher Copyright:
© 2020 American Society for Transplantation and Cellular Therapy

Funding

Jennifer Holter Chakrabarty and Wael Saber contributed equally as senior authors. Financial disclosure: 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 NHLBI and NCI; grant U24CA233032 from the NCI; grants OT3HL147741, R21HL140314, 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 R01HL131731 and R01HL126589 from the NHLBI; subawards from prime grant awards 5P01CA111412, 5R01HL129472, R01CA152108, 1R01HL131731, 1U01AI126612, and 1R01CA231141 from the National Institutes of Health; and commercial funds from Actinium Pharmaceuticals, Inc.; Adaptive Biotechnologies; Allovir, Inc.; Amgen, Inc.; anonymous donation to the Medical College of Wisconsin; Anthem, Inc.; Astellas Pharma US; Atara Biotherapeutics, Inc.; BARDA; Be the Match Foundation; bluebird bio, Inc.; Boston Children's Hospital; Bristol Myers Squibb Co.; Celgene Corp.; Children's Hospital of Los Angeles; Chimerix, Inc.; City of Hope Medical Center; CSL Behring; CytoSen Therapeutics, Inc.; Daiichi Sankyo Co. Ltd.; Dana Farber Cancer Institute; Enterprise Science and Computing, Inc.; Fred Hutchinson Cancer Research Center; Gamida-Cell, Ltd.; Genzyme; Gilead Sciences, Inc.; GlaxoSmithKline (GSK); HistoGenetics, Inc.; Immucor; Incyte Corporation; Janssen Biotech, Inc.; Janssen Pharmaceuticals, Inc.; Janssen Research & Development, LLC; Janssen Scientific Affairs, LLC; Japan Hematopoietic Cell Transplantation Data Center; Jazz Pharmaceuticals, Inc.; Karius, Inc.; Karyopharm Therapeutics, Inc.; Kite, a Gilead Company; Kyowa Kirin; Magenta Therapeutics; Mayo Clinic and Foundation Rochester; Medac GmbH; Mediware; Memorial Sloan Kettering Cancer Center; Merck & Company, Inc.; Mesoblast; MesoScale Diagnostics, Inc.; Millennium, the Takeda Oncology Co.; Miltenyi Biotec, Inc.; Mundipharma EDO; National Marrow Donor Program; Novartis Oncology; Novartis Pharmaceuticals Corporation; Omeros Corporation; Oncoimmune, Inc.; OptumHealth; Orca Biosystems, Inc.; PCORI; Pfizer, Inc.; Phamacyclics, LLC; PIRCHE AG; Regeneron Pharmaceuticals, Inc.; REGiMMUNE Corp.; Sanofi Genzyme; Seattle Genetics; Shire; Sobi, Inc.; Spectrum Pharmaceuticals, Inc.; St. Baldrick's Foundation; Swedish Orphan Biovitrum, Inc.; Takeda Oncology; The Medical College of Wisconsin; University of Minnesota; University of Pittsburgh; University of Texas, MD Anderson; University of Wisconsin-Madison; 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, Health Resources and Services Administration (HRSA), or any other agency of the US government. Conflict of interest statement: R.F.O. AstraZeneca; U.G. Incyte, Merck, Astellas, and Jazz Pharmaceuticals; G.O. Novartis, Bristol-Myers Squibb, Incyte, and Pfizer; H.L. Novartis and Bristol-Myers Squibb; J.C. Pfizer. All other authors declare no conflicts of interest. Authorship statement: S.S. J.H.C. and W.S. designed research, analyzed and interpreted the data, and wrote the paper. Y.L. and Z.-H.H. provided statistical analysis and contributed to writing the paper. K.M.W. H.M.L. R.V. M.A.K.-D. G.O. P.H.W, D.W. R.T.K. R.H. B.W. J.C. U.B. N.A.C. S.N. N.F. M.A. U.G. J.S. S.S. J.W.H. R.O. D.M. B.G. G.C.H. V.A. T.N. H.A.A. E.A. U.P. R.S. and B.L.S. contributed to research design, data analysis and interpretation, and writing the paper. Financial disclosure: See Acknowledgments on page 1142. Financial disclosure: 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 NHLBI and NCI; grant U24CA233032 from the NCI; grants OT3HL147741, R21HL140314, 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 R01HL131731 and R01HL126589 from the NHLBI; subawards from prime grant awards 5P01CA111412, 5R01HL129472, R01CA152108, 1R01HL131731, 1U01AI126612, and 1R01CA231141 from the National Institutes of Health; and commercial funds from Actinium Pharmaceuticals, Inc.; Adaptive Biotechnologies; Allovir, Inc.; Amgen, Inc.; anonymous donation to the Medical College of Wisconsin; Anthem, Inc.; Astellas Pharma US; Atara Biotherapeutics, Inc.; BARDA; Be the Match Foundation; bluebird bio, Inc.; Boston Children's Hospital; Bristol Myers Squibb Co.; Celgene Corp.; Children's Hospital of Los Angeles; Chimerix, Inc.; City of Hope Medical Center; CSL Behring; CytoSen Therapeutics, Inc.; Daiichi Sankyo Co., Ltd.; Dana Farber Cancer Institute; Enterprise Science and Computing, Inc.; Fred Hutchinson Cancer Research Center; Gamida-Cell, Ltd.; Genzyme; Gilead Sciences, Inc.; GlaxoSmithKline (GSK); HistoGenetics, Inc.; Immucor; Incyte Corporation; Janssen Biotech, Inc.; Janssen Pharmaceuticals, Inc.; Janssen Research & Development, LLC; Janssen Scientific Affairs, LLC; Japan Hematopoietic Cell Transplantation Data Center; Jazz Pharmaceuticals, Inc.; Karius, Inc.; Karyopharm Therapeutics, Inc.; Kite, a Gilead Company; Kyowa Kirin; Magenta Therapeutics; Mayo Clinic and Foundation Rochester; Medac GmbH; Mediware; Memorial Sloan Kettering Cancer Center; Merck & Company, Inc.; Mesoblast; MesoScale Diagnostics, Inc.; Millennium, the Takeda Oncology Co.; Miltenyi Biotec, Inc.; Mundipharma EDO; National Marrow Donor Program; Novartis Oncology; Novartis Pharmaceuticals Corporation; Omeros Corporation; Oncoimmune, Inc.; OptumHealth; Orca Biosystems, Inc.; PCORI; Pfizer, Inc.; Phamacyclics, LLC; PIRCHE AG; Regeneron Pharmaceuticals, Inc.; REGiMMUNE Corp.; Sanofi Genzyme; Seattle Genetics; Shire; Sobi, Inc.; Spectrum Pharmaceuticals, Inc.; St. Baldrick's Foundation; Swedish Orphan Biovitrum, Inc.; Takeda Oncology; The Medical College of Wisconsin; University of Minnesota; University of Pittsburgh; University of Texas, MD Anderson; University of Wisconsin-Madison; 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, Health Resources and Services Administration (HRSA), or any other agency of the US government.

FundersFunder number
Actinium Pharmaceuticals, Inc.
Bristol-Myers Squibb
CytoSen Therapeutics, Inc.
Dana-Farber Cancer Institute
Department of the Navy
Enterprise Science and Computing, Inc.
Gilead Company
Hope Medical Center
Incyte Corporation
Janssen Scientific Affairs LLC
Magenta Therapeutics
US Government Accountability Office
Texas AandM University
National Institutes of Health (NIH)
U.S. Department of Defense
Office of Naval Research Naval Academy1R01CA231141, 5R01HL129472, 1U01AI126612, 5P01CA111412, SC1MC31881-01-00, 1R01HL131731, R01CA152108
National Heart, Lung, and Blood Institute (NHLBI)U24HL138660, R01HL131731, R01HL126589, U01HL128568, R21HL140314
National Childhood Cancer Registry – National Cancer InstituteU24CA076518, U24CA233032
National Institute of Allergy and Infectious DiseasesOT3HL147741, HHSH250201700006C
Health Resources and Services AdministrationN00014-17-1-2850, N00014-18-1-2888
Mayo Clinic Rochester
Bristol-Myers Squibb
Pfizer
Astellas Pharma Inc.
Merck
Gilead Sciences
Janssen Biotech
North Carolina GlaxoSmithKline Foundation
University of Wisconsin-Madison
Minnesota State University-Mankato
University of Texas Anderson Cancer Center
University of Pittsburgh Medical Center, Children's Hospital of Pittsburgh
CSL Behring GmbH
Janssen Pharmaceuticals
Jazz Pharmaceuticals
Daiichi Sankyo Company, Limited
Kyowa Hakko Kirin

    Keywords

    • Chronic myeloid leukemia
    • Donor lymphocyte infusion
    • Hematopoietic cell transplantation
    • Tyrosine kinase inhibitor

    ASJC Scopus subject areas

    • Hematology
    • Transplantation

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