Risk Factors for Graft-versus-Host Disease in Haploidentical Hematopoietic Cell Transplantation Using Post-Transplant Cyclophosphamide

Annie Im; Armin Rashidi; Tao Wang; Michael Hemmer; Margaret L. MacMillan; Joseph Pidala; Madan Jagasia; Steven Pavletic; Navneet S. Majhail; Daniel Weisdorf; Hisham Abdel-Azim; Vaibhav Agrawal; A. Samer Al-Homsi; Mahmoud Aljurf; Medhat Askar; Jeffery J. Auletta; Asad Bashey; Amer Beitinjaneh; Vijaya Raj Bhatt; Michael Byrne; Jean Yves Cahn; Mitchell Cairo; Paul Castillo; Jan Cerny; Saurabh Chhabra; Hannah Choe; Stefan Ciurea; Andrew Daly; Miguel Angel Diaz Perez; Nosha Farhadfar; Shahinaz M. Gadalla; Robert Gale; Siddhartha Ganguly; Usama Gergis; Rabi Hanna; Peiman Hematti; Roger Herzig; Gerhard C. Hildebrandt; Deepesh P. Lad; Catherine Lee; Leslie Lehmann; Lazaros Lekakis; Rammurti T. Kamble; Mohamed A. Kharfan-Dabaja; Pooja Khandelwal; Rodrigo Martino; Hemant S. Murthy; Taiga Nishihori; Tracey A. O'Brien; Richard F. Olsson; Sagar S. Patel; Miguel Angel Perales; Tim Prestidge; Muna Qayed; Rizwan Romee; Hélène Schoemans; Sachiko Seo; Akshay Sharma; Melhem Solh; Roger Strair; Takanori Teshima; Alvaro Urbano-Ispizua; Marjolein Van der Poel; Ravi Vij; John L. Wagner; Basem William; Baldeep Wirk; Jean A. Yared; Steve R. Spellman; Mukta Arora; Betty K. Hamilton

doi:10.1016/j.bbmt.2020.05.001

Risk Factors for Graft-versus-Host Disease in Haploidentical Hematopoietic Cell Transplantation Using Post-Transplant Cyclophosphamide

Annie Im, Armin Rashidi, Tao Wang, Michael Hemmer, Margaret L. MacMillan, Joseph Pidala, Madan Jagasia, Steven Pavletic, Navneet S. Majhail, Daniel Weisdorf, Hisham Abdel-Azim, Vaibhav Agrawal, A. Samer Al-Homsi, Mahmoud Aljurf, Medhat Askar, Jeffery J. Auletta, Asad Bashey, Amer Beitinjaneh, Vijaya Raj Bhatt, Michael ByrneJean Yves Cahn, Mitchell Cairo, Paul Castillo, Jan Cerny, Saurabh Chhabra, Hannah Choe, Stefan Ciurea, Andrew Daly, Miguel Angel Diaz Perez, Nosha Farhadfar, Shahinaz M. Gadalla, Robert Gale, Siddhartha Ganguly, Usama Gergis, Rabi Hanna, Peiman Hematti, Roger Herzig, Gerhard C. Hildebrandt, Deepesh P. Lad, Catherine Lee, Leslie Lehmann, Lazaros Lekakis, Rammurti T. Kamble, Mohamed A. Kharfan-Dabaja, Pooja Khandelwal, Rodrigo Martino, Hemant S. Murthy, Taiga Nishihori, Tracey A. O'Brien, Richard F. Olsson, Sagar S. Patel, Miguel Angel Perales, Tim Prestidge, Muna Qayed, Rizwan Romee, Hélène Schoemans, Sachiko Seo, Akshay Sharma, Melhem Solh, Roger Strair, Takanori Teshima, Alvaro Urbano-Ispizua, Marjolein Van der Poel, Ravi Vij, John L. Wagner, Basem William, Baldeep Wirk, Jean A. Yared, Steve R. Spellman, Mukta Arora, Betty K. Hamilton

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

27 Scopus citations

Abstract

Post-transplant cyclophosphamide (PTCy) has significantly increased the successful use of haploidentical donors with a relatively low incidence of graft-versus-host disease (GVHD). Given its increasing use, we sought to determine risk factors for GVHD after haploidentical hematopoietic cell transplantation (haplo-HCT) using PTCy. Data from the Center for International Blood and Marrow Transplant Research on adult patients with acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, or chronic myeloid leukemia who underwent PTCy-based haplo-HCT (2013 to 2016) were analyzed and categorized into 4 groups based on myeloablative (MA) or reduced-intensity conditioning (RIC) and bone marrow (BM) or peripheral blood (PB) graft source. In total, 646 patients were identified (MA-BM = 79, MA-PB = 183, RIC-BM = 192, RIC-PB = 192). The incidence of grade 2 to 4 acute GVHD at 6 months was highest in MA-PB (44%), followed by RIC-PB (36%), MA-BM (36%), and RIC-BM (30%) (P =.002). The incidence of chronic GVHD at 1 year was 40%, 34%, 24%, and 20%, respectively (P <.001). In multivariable analysis, there was no impact of stem cell source or conditioning regimen on grade 2 to 4 acute GVHD; however, older donor age (30 to 49 versus <29 years) was significantly associated with higher rates of grade 2 to 4 acute GVHD (hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.11 to 2.12; P =.01). In contrast, PB compared to BM as a stem cell source was a significant risk factor for the development of chronic GVHD (HR, 1.70; 95% CI, 1.11 to 2.62; P =.01) in the RIC setting. There were no differences in relapse or overall survival between groups. Donor age and graft source are risk factors for acute and chronic GVHD, respectively, after PTCy-based haplo-HCT. Our results indicate that in RIC haplo-HCT, the risk of chronic GVHD is higher with PB stem cells, without any difference in relapse or overall survival.

Original language	English (US)
Pages (from-to)	1459-1468
Number of pages	10
Journal	Biology of Blood and Marrow Transplantation
Volume	26
Issue number	8
DOIs	https://doi.org/10.1016/j.bbmt.2020.05.001
State	Published - Aug 2020

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 NHLBI and NCI; grant U24CA233032 from the NCI; grants OT3HL147741, R21HL140314, and U01HL128568 from the NHLBI; contract HHSH250201700006C with 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 HRSA; subawards from prime grant awards R01HL131731 and R01HL126589 from 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, HRSA, or any other agency of the US government.

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Im, A., Rashidi, A., Wang, T., Hemmer, M., MacMillan, M. L., Pidala, J., Jagasia, M., Pavletic, S., Majhail, N. S., Weisdorf, D., Abdel-Azim, H., Agrawal, V., Al-Homsi, A. S., Aljurf, M., Askar, M., Auletta, J. J., Bashey, A., Beitinjaneh, A., Bhatt, V. R., ... Hamilton, B. K. (2020). Risk Factors for Graft-versus-Host Disease in Haploidentical Hematopoietic Cell Transplantation Using Post-Transplant Cyclophosphamide. Biology of Blood and Marrow Transplantation, 26(8), 1459-1468. https://doi.org/10.1016/j.bbmt.2020.05.001

Im, A, Rashidi, A, Wang, T, Hemmer, M, MacMillan, ML, Pidala, J, Jagasia, M, Pavletic, S, Majhail, NS, Weisdorf, D, Abdel-Azim, H, Agrawal, V, Al-Homsi, AS, Aljurf, M, Askar, M, Auletta, JJ, Bashey, A, Beitinjaneh, A, Bhatt, VR, Byrne, M, Cahn, JY, Cairo, M, Castillo, P, Cerny, J, Chhabra, S, Choe, H, Ciurea, S, Daly, A, Perez, MAD, Farhadfar, N, Gadalla, SM, Gale, R, Ganguly, S, Gergis, U, Hanna, R, Hematti, P, Herzig, R, Hildebrandt, GC, Lad, DP, Lee, C, Lehmann, L, Lekakis, L, Kamble, RT, Kharfan-Dabaja, MA, Khandelwal, P, Martino, R, Murthy, HS, Nishihori, T, O'Brien, TA, Olsson, RF, Patel, SS, Perales, MA, Prestidge, T, Qayed, M, Romee, R, Schoemans, H, Seo, S, Sharma, A, Solh, M, Strair, R, Teshima, T, Urbano-Ispizua, A, Van der Poel, M, Vij, R, Wagner, JL, William, B, Wirk, B, Yared, JA, Spellman, SR, Arora, M & Hamilton, BK 2020, 'Risk Factors for Graft-versus-Host Disease in Haploidentical Hematopoietic Cell Transplantation Using Post-Transplant Cyclophosphamide', Biology of Blood and Marrow Transplantation, vol. 26, no. 8, pp. 1459-1468. https://doi.org/10.1016/j.bbmt.2020.05.001

@article{4483c7916e54419bbc470e43391db807,

title = "Risk Factors for Graft-versus-Host Disease in Haploidentical Hematopoietic Cell Transplantation Using Post-Transplant Cyclophosphamide",

abstract = "Post-transplant cyclophosphamide (PTCy) has significantly increased the successful use of haploidentical donors with a relatively low incidence of graft-versus-host disease (GVHD). Given its increasing use, we sought to determine risk factors for GVHD after haploidentical hematopoietic cell transplantation (haplo-HCT) using PTCy. Data from the Center for International Blood and Marrow Transplant Research on adult patients with acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, or chronic myeloid leukemia who underwent PTCy-based haplo-HCT (2013 to 2016) were analyzed and categorized into 4 groups based on myeloablative (MA) or reduced-intensity conditioning (RIC) and bone marrow (BM) or peripheral blood (PB) graft source. In total, 646 patients were identified (MA-BM = 79, MA-PB = 183, RIC-BM = 192, RIC-PB = 192). The incidence of grade 2 to 4 acute GVHD at 6 months was highest in MA-PB (44%), followed by RIC-PB (36%), MA-BM (36%), and RIC-BM (30%) (P =.002). The incidence of chronic GVHD at 1 year was 40%, 34%, 24%, and 20%, respectively (P <.001). In multivariable analysis, there was no impact of stem cell source or conditioning regimen on grade 2 to 4 acute GVHD; however, older donor age (30 to 49 versus <29 years) was significantly associated with higher rates of grade 2 to 4 acute GVHD (hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.11 to 2.12; P =.01). In contrast, PB compared to BM as a stem cell source was a significant risk factor for the development of chronic GVHD (HR, 1.70; 95% CI, 1.11 to 2.62; P =.01) in the RIC setting. There were no differences in relapse or overall survival between groups. Donor age and graft source are risk factors for acute and chronic GVHD, respectively, after PTCy-based haplo-HCT. Our results indicate that in RIC haplo-HCT, the risk of chronic GVHD is higher with PB stem cells, without any difference in relapse or overall survival.",

author = "Annie Im and Armin Rashidi and Tao Wang and Michael Hemmer and MacMillan, {Margaret L.} and Joseph Pidala and Madan Jagasia and Steven Pavletic and Majhail, {Navneet S.} and Daniel Weisdorf and Hisham Abdel-Azim and Vaibhav Agrawal and Al-Homsi, {A. Samer} and Mahmoud Aljurf and Medhat Askar and Auletta, {Jeffery J.} and Asad Bashey and Amer Beitinjaneh and Bhatt, {Vijaya Raj} and Michael Byrne and Cahn, {Jean Yves} and Mitchell Cairo and Paul Castillo and Jan Cerny and Saurabh Chhabra and Hannah Choe and Stefan Ciurea and Andrew Daly and Perez, {Miguel Angel Diaz} and Nosha Farhadfar and Gadalla, {Shahinaz M.} and Robert Gale and Siddhartha Ganguly and Usama Gergis and Rabi Hanna and Peiman Hematti and Roger Herzig and Hildebrandt, {Gerhard C.} and Lad, {Deepesh P.} and Catherine Lee and Leslie Lehmann and Lazaros Lekakis and Kamble, {Rammurti T.} and Kharfan-Dabaja, {Mohamed A.} and Pooja Khandelwal and Rodrigo Martino and Murthy, {Hemant S.} and Taiga Nishihori and O'Brien, {Tracey A.} and Olsson, {Richard F.} and Patel, {Sagar S.} and Perales, {Miguel Angel} and Tim Prestidge and Muna Qayed and Rizwan Romee and H{\'e}l{\`e}ne Schoemans and Sachiko Seo and Akshay Sharma and Melhem Solh and Roger Strair and Takanori Teshima and Alvaro Urbano-Ispizua and {Van der Poel}, Marjolein and Ravi Vij and Wagner, {John L.} and Basem William and Baldeep Wirk and Yared, {Jean A.} and Spellman, {Steve R.} and Mukta Arora and Hamilton, {Betty K.}",

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 NHLBI and NCI; grant U24CA233032 from the NCI; grants OT3HL147741, R21HL140314, and U01HL128568 from the NHLBI; contract HHSH250201700006C with 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 HRSA; subawards from prime grant awards R01HL131731 and R01HL126589 from 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, HRSA, or any other agency of the US government. ",

year = "2020",

month = aug,

doi = "10.1016/j.bbmt.2020.05.001",

language = "English (US)",

volume = "26",

pages = "1459--1468",

journal = "Biology of Blood and Marrow Transplantation",

issn = "1083-8791",

publisher = "Elsevier Inc.",

number = "8",

}

TY - JOUR

T1 - Risk Factors for Graft-versus-Host Disease in Haploidentical Hematopoietic Cell Transplantation Using Post-Transplant Cyclophosphamide

AU - Im, Annie

AU - Rashidi, Armin

AU - Wang, Tao

AU - Hemmer, Michael

AU - MacMillan, Margaret L.

AU - Pidala, Joseph

AU - Jagasia, Madan

AU - Pavletic, Steven

AU - Majhail, Navneet S.

AU - Weisdorf, Daniel

AU - Abdel-Azim, Hisham

AU - Agrawal, Vaibhav

AU - Al-Homsi, A. Samer

AU - Aljurf, Mahmoud

AU - Askar, Medhat

AU - Auletta, Jeffery J.

AU - Bashey, Asad

AU - Beitinjaneh, Amer

AU - Bhatt, Vijaya Raj

AU - Byrne, Michael

AU - Cahn, Jean Yves

AU - Cairo, Mitchell

AU - Castillo, Paul

AU - Cerny, Jan

AU - Chhabra, Saurabh

AU - Choe, Hannah

AU - Ciurea, Stefan

AU - Daly, Andrew

AU - Perez, Miguel Angel Diaz

AU - Farhadfar, Nosha

AU - Gadalla, Shahinaz M.

AU - Gale, Robert

AU - Ganguly, Siddhartha

AU - Gergis, Usama

AU - Hanna, Rabi

AU - Hematti, Peiman

AU - Herzig, Roger

AU - Hildebrandt, Gerhard C.

AU - Lad, Deepesh P.

AU - Lee, Catherine

AU - Lehmann, Leslie

AU - Lekakis, Lazaros

AU - Kamble, Rammurti T.

AU - Kharfan-Dabaja, Mohamed A.

AU - Khandelwal, Pooja

AU - Martino, Rodrigo

AU - Murthy, Hemant S.

AU - Nishihori, Taiga

AU - O'Brien, Tracey A.

AU - Olsson, Richard F.

AU - Patel, Sagar S.

AU - Perales, Miguel Angel

AU - Prestidge, Tim

AU - Qayed, Muna

AU - Romee, Rizwan

AU - Schoemans, Hélène

AU - Seo, Sachiko

AU - Sharma, Akshay

AU - Solh, Melhem

AU - Strair, Roger

AU - Teshima, Takanori

AU - Urbano-Ispizua, Alvaro

AU - Van der Poel, Marjolein

AU - Vij, Ravi

AU - Wagner, John L.

AU - William, Basem

AU - Wirk, Baldeep

AU - Yared, Jean A.

AU - Spellman, Steve R.

AU - Arora, Mukta

AU - Hamilton, Betty K.

N1 - 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 NHLBI and NCI; grant U24CA233032 from the NCI; grants OT3HL147741, R21HL140314, and U01HL128568 from the NHLBI; contract HHSH250201700006C with 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 HRSA; subawards from prime grant awards R01HL131731 and R01HL126589 from 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, HRSA, or any other agency of the US government.

PY - 2020/8

Y1 - 2020/8

N2 - Post-transplant cyclophosphamide (PTCy) has significantly increased the successful use of haploidentical donors with a relatively low incidence of graft-versus-host disease (GVHD). Given its increasing use, we sought to determine risk factors for GVHD after haploidentical hematopoietic cell transplantation (haplo-HCT) using PTCy. Data from the Center for International Blood and Marrow Transplant Research on adult patients with acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, or chronic myeloid leukemia who underwent PTCy-based haplo-HCT (2013 to 2016) were analyzed and categorized into 4 groups based on myeloablative (MA) or reduced-intensity conditioning (RIC) and bone marrow (BM) or peripheral blood (PB) graft source. In total, 646 patients were identified (MA-BM = 79, MA-PB = 183, RIC-BM = 192, RIC-PB = 192). The incidence of grade 2 to 4 acute GVHD at 6 months was highest in MA-PB (44%), followed by RIC-PB (36%), MA-BM (36%), and RIC-BM (30%) (P =.002). The incidence of chronic GVHD at 1 year was 40%, 34%, 24%, and 20%, respectively (P <.001). In multivariable analysis, there was no impact of stem cell source or conditioning regimen on grade 2 to 4 acute GVHD; however, older donor age (30 to 49 versus <29 years) was significantly associated with higher rates of grade 2 to 4 acute GVHD (hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.11 to 2.12; P =.01). In contrast, PB compared to BM as a stem cell source was a significant risk factor for the development of chronic GVHD (HR, 1.70; 95% CI, 1.11 to 2.62; P =.01) in the RIC setting. There were no differences in relapse or overall survival between groups. Donor age and graft source are risk factors for acute and chronic GVHD, respectively, after PTCy-based haplo-HCT. Our results indicate that in RIC haplo-HCT, the risk of chronic GVHD is higher with PB stem cells, without any difference in relapse or overall survival.

AB - Post-transplant cyclophosphamide (PTCy) has significantly increased the successful use of haploidentical donors with a relatively low incidence of graft-versus-host disease (GVHD). Given its increasing use, we sought to determine risk factors for GVHD after haploidentical hematopoietic cell transplantation (haplo-HCT) using PTCy. Data from the Center for International Blood and Marrow Transplant Research on adult patients with acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, or chronic myeloid leukemia who underwent PTCy-based haplo-HCT (2013 to 2016) were analyzed and categorized into 4 groups based on myeloablative (MA) or reduced-intensity conditioning (RIC) and bone marrow (BM) or peripheral blood (PB) graft source. In total, 646 patients were identified (MA-BM = 79, MA-PB = 183, RIC-BM = 192, RIC-PB = 192). The incidence of grade 2 to 4 acute GVHD at 6 months was highest in MA-PB (44%), followed by RIC-PB (36%), MA-BM (36%), and RIC-BM (30%) (P =.002). The incidence of chronic GVHD at 1 year was 40%, 34%, 24%, and 20%, respectively (P <.001). In multivariable analysis, there was no impact of stem cell source or conditioning regimen on grade 2 to 4 acute GVHD; however, older donor age (30 to 49 versus <29 years) was significantly associated with higher rates of grade 2 to 4 acute GVHD (hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.11 to 2.12; P =.01). In contrast, PB compared to BM as a stem cell source was a significant risk factor for the development of chronic GVHD (HR, 1.70; 95% CI, 1.11 to 2.62; P =.01) in the RIC setting. There were no differences in relapse or overall survival between groups. Donor age and graft source are risk factors for acute and chronic GVHD, respectively, after PTCy-based haplo-HCT. Our results indicate that in RIC haplo-HCT, the risk of chronic GVHD is higher with PB stem cells, without any difference in relapse or overall survival.

UR - http://www.scopus.com/inward/record.url?scp=85086477294&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85086477294&partnerID=8YFLogxK

U2 - 10.1016/j.bbmt.2020.05.001

DO - 10.1016/j.bbmt.2020.05.001

M3 - Article

C2 - 32434056

AN - SCOPUS:85086477294

SN - 1083-8791

VL - 26

SP - 1459

EP - 1468

JO - Biology of Blood and Marrow Transplantation

JF - Biology of Blood and Marrow Transplantation

IS - 8

ER -

Risk Factors for Graft-versus-Host Disease in Haploidentical Hematopoietic Cell Transplantation Using Post-Transplant Cyclophosphamide

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