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 Gergis; Jeffrey 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

doi:10.1016/j.bbmt.2020.02.006

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 journal › Article › peer-review

9 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 language	English
Pages (from-to)	1137-1143
Number of pages	7
Journal	Biology of Blood and Marrow Transplantation
Volume	26
Issue number	6
DOIs	https://doi.org/10.1016/j.bbmt.2020.02.006
State	Published - Jun 2020

Bibliographical note

Funding Information:
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.

Funding Information:
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.

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

Keywords

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

ASJC Scopus subject areas

Hematology
Transplantation

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10.1016/j.bbmt.2020.02.006

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Schmidt, S., Liu, Y., Hu, Z. H., Williams, K. M., Lazarus, H. M., Vij, R., Kharfan-Dabaja, M. A., Ortí, G., Wiernik, P. H., Weisdorf, D., Kamble, R. T., Herzig, R., Wirk, B., Cerny, J., Bacher, U., Chaudhri, N. A., Nathan, S., Farhadfar, N., Aljurf, M., ... Saber, W. (2020). 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. Biology of Blood and Marrow Transplantation, 26(6), 1137-1143. https://doi.org/10.1016/j.bbmt.2020.02.006

Schmidt, Sarah ; Liu, Ying ; Hu, Zhen Huan et al. / 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. In: Biology of Blood and Marrow Transplantation. 2020 ; Vol. 26, No. 6. pp. 1137-1143.

@article{09dcb74902c9460ea488d80336cc0340,

title = "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",

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.",

keywords = "Chronic myeloid leukemia, Donor lymphocyte infusion, Hematopoietic cell transplantation, Tyrosine kinase inhibitor",

author = "Sarah Schmidt and Ying Liu and Hu, {Zhen Huan} and Williams, {Kirsten M.} and Lazarus, {Hillard M.} and Ravi Vij and Kharfan-Dabaja, {Mohamed A.} and Guillermo Ort{\'i} and Wiernik, {Peter H.} and Daniel Weisdorf and Kamble, {Rammurti T.} and Roger Herzig and Baldeep Wirk and Jan Cerny and Ulrike Bacher and Chaudhri, {Naeem A.} and Sunita Nathan and Nosha Farhadfar and Mahmoud Aljurf and Usama Gergis and Jeffrey Szer and Sachiko Seo and Hsu, {Jack W.} and Olsson, {Richard F.} and Dipnarine Maharaj and Biju George and Hildebrandt, {Gerhard C.} and Vaibhav Agrawal and Taiga Nishihori and Hisham Abdel-Azim and Edwin Alyea and Uday Popat and Ronald Sobecks and Scott, {Bart L.} and {Holter Chakrabarty}, Jennifer and Wael Saber",

note = "Funding Information: 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. Funding Information: 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. Publisher Copyright: {\textcopyright} 2020 American Society for Transplantation and Cellular Therapy",

year = "2020",

month = jun,

doi = "10.1016/j.bbmt.2020.02.006",

language = "English",

volume = "26",

pages = "1137--1143",

number = "6",

}

Schmidt, S, Liu, Y, Hu, ZH, Williams, KM, Lazarus, HM, Vij, R, Kharfan-Dabaja, MA, Ortí, G, Wiernik, PH, Weisdorf, D, Kamble, RT, Herzig, R, Wirk, B, Cerny, J, Bacher, U, Chaudhri, NA, Nathan, S, Farhadfar, N, Aljurf, M, Gergis, U, Szer, J, Seo, S, Hsu, JW, Olsson, RF, Maharaj, D, George, B, Hildebrandt, GC, Agrawal, V, Nishihori, T, Abdel-Azim, H, Alyea, E, Popat, U, Sobecks, R, Scott, BL, Holter Chakrabarty, J & Saber, W 2020, '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', Biology of Blood and Marrow Transplantation, vol. 26, no. 6, pp. 1137-1143. https://doi.org/10.1016/j.bbmt.2020.02.006

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. / Schmidt, Sarah; Liu, Ying; Hu, Zhen Huan et al.

In: Biology of Blood and Marrow Transplantation, Vol. 26, No. 6, 06.2020, p. 1137-1143.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - 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

T2 - Role of DLI in Post-HCT Relapse for CML in the TKI Era

AU - Schmidt, Sarah

AU - Liu, Ying

AU - Hu, Zhen Huan

AU - Williams, Kirsten M.

AU - Lazarus, Hillard M.

AU - Vij, Ravi

AU - Kharfan-Dabaja, Mohamed A.

AU - Ortí, Guillermo

AU - Wiernik, Peter H.

AU - Weisdorf, Daniel

AU - Kamble, Rammurti T.

AU - Herzig, Roger

AU - Wirk, Baldeep

AU - Cerny, Jan

AU - Bacher, Ulrike

AU - Chaudhri, Naeem A.

AU - Nathan, Sunita

AU - Farhadfar, Nosha

AU - Aljurf, Mahmoud

AU - Gergis, Usama

AU - Szer, Jeffrey

AU - Seo, Sachiko

AU - Hsu, Jack W.

AU - Olsson, Richard F.

AU - Maharaj, Dipnarine

AU - George, Biju

AU - Hildebrandt, Gerhard C.

AU - Agrawal, Vaibhav

AU - Nishihori, Taiga

AU - Abdel-Azim, Hisham

AU - Alyea, Edwin

AU - Popat, Uday

AU - Sobecks, Ronald

AU - Scott, Bart L.

AU - Holter Chakrabarty, Jennifer

AU - Saber, Wael

N1 - Funding Information: 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. Funding Information: 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. Publisher Copyright: © 2020 American Society for Transplantation and Cellular Therapy

PY - 2020/6

Y1 - 2020/6

N2 - 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.

AB - 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.

KW - Chronic myeloid leukemia

KW - Donor lymphocyte infusion

KW - Hematopoietic cell transplantation

KW - Tyrosine kinase inhibitor

UR - http://www.scopus.com/inward/record.url?scp=85081933393&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85081933393&partnerID=8YFLogxK

U2 - 10.1016/j.bbmt.2020.02.006

DO - 10.1016/j.bbmt.2020.02.006

M3 - Article

C2 - 32062061

AN - SCOPUS:85081933393

VL - 26

SP - 1137

EP - 1143

IS - 6

ER -

Schmidt S, Liu Y, Hu ZH, Williams KM, Lazarus HM, Vij R et al. 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. Biology of Blood and Marrow Transplantation. 2020 Jun;26(6):1137-1143. doi: 10.1016/j.bbmt.2020.02.006

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

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