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

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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

ASJC Scopus subject areas

Hematology
Transplantation

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10.1016/j.bbmt.2020.05.001

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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{25b822025b8a4b75869074a91f8ec3c7,

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

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",

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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.

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.

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

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