Graft-versus-Host Disease Prophylaxis with Post-Transplantation Cyclophosphamide versus Cyclosporine A and Methotrexate in Matched Sibling Donor Transplantation

Arnon Nagler; Myriam Labopin; Bhagirathbhai Dholaria; Depei Wu; Goda Choi; Mahmoud Aljurf; Fabio Ciceri; Tobias Gedde-Dahl; Ellen Meijer; Riitta Niittyvuopio; Sergey Bondarenko; Jean Henri Bourhis; Jan J. Cornelissen; Gerard Socié; Yener Koc; Jonathan Canaani; Bipin Savani; Gesine Bug; Alexandros Spyridonidis; Sebastian Giebel; Eolia Brissot; Ali Bazarbachi; Jordi Esteve; Mohamad Mohty

doi:10.1016/j.jtct.2021.11.013

Graft-versus-Host Disease Prophylaxis with Post-Transplantation Cyclophosphamide versus Cyclosporine A and Methotrexate in Matched Sibling Donor Transplantation

Arnon Nagler, Myriam Labopin, Bhagirathbhai Dholaria^*, Depei Wu, Goda Choi, Mahmoud Aljurf, Fabio Ciceri, Tobias Gedde-Dahl, Ellen Meijer, Riitta Niittyvuopio, Sergey Bondarenko, Jean Henri Bourhis, Jan J. Cornelissen, Gerard Socié, Yener Koc, Jonathan Canaani, Bipin Savani, Gesine Bug, Alexandros Spyridonidis, Sebastian GiebelEolia Brissot, Ali Bazarbachi, Jordi Esteve, Mohamad Mohty

^*Corresponding author for this work

Hematology

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

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Abstract

Cyclosporine A (CSA) and methotrexate (MTX) is the standard graft-versus-host disease (GVHD) prophylaxis regimen for matched sibling donor (MSD) allogeneic hematopoietic cell transplantation (allo-HCT). Recently, post-transplantation cyclophosphamide (PTCy) has been shown to be effective in GVHD prevention. In this registry-based study, we compared outcomes of 118 patients treated with PTCy and 1202 patients with CSA/MTX who underwent MSD allo-HCT for acute myelogenous leukemia. In a matched-pair analysis, PTCy was associated with a higher incidence of relapse at 2 years compared with CSA/MTX (41.1% versus 21.3%; P =.039). The incidences of day +180 grade II-IV acute GVHD and 2-year chronic GVHD were comparable in the PTCy and CSA/MTX arms (25.2% versus 25.4% [P =.90] and 42.6% versus 42.6% [P =.84], respectively). Similarly, 2-year leukemia-free survival (LFS; 54.4% versus 74.32%; P =.052), overall survival (OS; 70.6% versus 79.7%; P =.15), and GVHD-free relapse-free survival (GRFS; 38.1% versus 52.5%; P =.49) were not statistically different in the 2 arms. Our data show that GVHD prophylaxis with PTCy is feasible, resulting in similar incidences of GVHD, GRFS, LFS, and OS as seen with conventional CSA/MTX in patients undergoing allo-HCT from an MSD. The higher rate of relapse observed with PTCy needs further evaluation in a prospective study.

Original language	English
Pages (from-to)	86.e1-86.e8
Journal	Transplantation and Cellular Therapy
Volume	28
Issue number	2
DOIs	https://doi.org/10.1016/j.jtct.2021.11.013
Publication status	Published - Feb 2022

Bibliographical note

Funding Information:
The authors thank the EBMT centers and national registries for contributing patient information and data collection. Supporting information is available at the EBMT website ( www.ebmt.org). Reporting institutions included in this study are available in the Online Supporting Information Appendix. There is no relevant funding to report. A.N. M.M. and M.L. contributed to the conception and design of the study; M.L. analyzed the data; B.D. B.N.S. A.N. M.L. M.M. contributed to the writing of the manuscript; all authors critically reviewed the manuscript and approved the final version. A.N. and B.D. contributed equally to this work and should be considered co-first authors. Requests for the raw data used in this study should be addressed to M.L.

Publisher Copyright:
© 2021 The American Society for Transplantation and Cellular Therapy

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Graft-versus-Host Disease Prophylaxis with Post-Transplantation Cyclophosphamide versus Cyclosporine A and Methotrexate in Matched Sibling Donor TransplantationFinal published version, 1.03 MBLicence: CC BY-NC-ND

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Nagler, A., Labopin, M., Dholaria, B., Wu, D., Choi, G., Aljurf, M., Ciceri, F., Gedde-Dahl, T., Meijer, E., Niittyvuopio, R., Bondarenko, S., Bourhis, J. H., Cornelissen, J. J., Socié, G., Koc, Y., Canaani, J., Savani, B., Bug, G., Spyridonidis, A., ... Mohty, M. (2022). Graft-versus-Host Disease Prophylaxis with Post-Transplantation Cyclophosphamide versus Cyclosporine A and Methotrexate in Matched Sibling Donor Transplantation. Transplantation and Cellular Therapy, 28(2), 86.e1-86.e8. https://doi.org/10.1016/j.jtct.2021.11.013

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title = "Graft-versus-Host Disease Prophylaxis with Post-Transplantation Cyclophosphamide versus Cyclosporine A and Methotrexate in Matched Sibling Donor Transplantation",

abstract = "Cyclosporine A (CSA) and methotrexate (MTX) is the standard graft-versus-host disease (GVHD) prophylaxis regimen for matched sibling donor (MSD) allogeneic hematopoietic cell transplantation (allo-HCT). Recently, post-transplantation cyclophosphamide (PTCy) has been shown to be effective in GVHD prevention. In this registry-based study, we compared outcomes of 118 patients treated with PTCy and 1202 patients with CSA/MTX who underwent MSD allo-HCT for acute myelogenous leukemia. In a matched-pair analysis, PTCy was associated with a higher incidence of relapse at 2 years compared with CSA/MTX (41.1% versus 21.3%; P =.039). The incidences of day +180 grade II-IV acute GVHD and 2-year chronic GVHD were comparable in the PTCy and CSA/MTX arms (25.2% versus 25.4% [P =.90] and 42.6% versus 42.6% [P =.84], respectively). Similarly, 2-year leukemia-free survival (LFS; 54.4% versus 74.32%; P =.052), overall survival (OS; 70.6% versus 79.7%; P =.15), and GVHD-free relapse-free survival (GRFS; 38.1% versus 52.5%; P =.49) were not statistically different in the 2 arms. Our data show that GVHD prophylaxis with PTCy is feasible, resulting in similar incidences of GVHD, GRFS, LFS, and OS as seen with conventional CSA/MTX in patients undergoing allo-HCT from an MSD. The higher rate of relapse observed with PTCy needs further evaluation in a prospective study.",

author = "Arnon Nagler and Myriam Labopin and Bhagirathbhai Dholaria and Depei Wu and Goda Choi and Mahmoud Aljurf and Fabio Ciceri and Tobias Gedde-Dahl and Ellen Meijer and Riitta Niittyvuopio and Sergey Bondarenko and Bourhis, {Jean Henri} and Cornelissen, {Jan J.} and Gerard Soci{\'e} and Yener Koc and Jonathan Canaani and Bipin Savani and Gesine Bug and Alexandros Spyridonidis and Sebastian Giebel and Eolia Brissot and Ali Bazarbachi and Jordi Esteve and Mohamad Mohty",

note = "Funding Information: The authors thank the EBMT centers and national registries for contributing patient information and data collection. Supporting information is available at the EBMT website ( www.ebmt.org). Reporting institutions included in this study are available in the Online Supporting Information Appendix. There is no relevant funding to report. A.N. M.M. and M.L. contributed to the conception and design of the study; M.L. analyzed the data; B.D. B.N.S. A.N. M.L. M.M. contributed to the writing of the manuscript; all authors critically reviewed the manuscript and approved the final version. A.N. and B.D. contributed equally to this work and should be considered co-first authors. Requests for the raw data used in this study should be addressed to M.L. Publisher Copyright: {\textcopyright} 2021 The American Society for Transplantation and Cellular Therapy",

year = "2022",

month = feb,

doi = "10.1016/j.jtct.2021.11.013",

language = "English",

volume = "28",

pages = "86.e1--86.e8",

journal = "Transplantation and Cellular Therapy",

issn = "2666-6367",

publisher = "Elsevier Inc.",

number = "2",

}

Nagler, A, Labopin, M, Dholaria, B, Wu, D, Choi, G, Aljurf, M, Ciceri, F, Gedde-Dahl, T, Meijer, E, Niittyvuopio, R, Bondarenko, S, Bourhis, JH, Cornelissen, JJ, Socié, G, Koc, Y, Canaani, J, Savani, B, Bug, G, Spyridonidis, A, Giebel, S, Brissot, E, Bazarbachi, A, Esteve, J & Mohty, M 2022, 'Graft-versus-Host Disease Prophylaxis with Post-Transplantation Cyclophosphamide versus Cyclosporine A and Methotrexate in Matched Sibling Donor Transplantation', Transplantation and Cellular Therapy, vol. 28, no. 2, pp. 86.e1-86.e8. https://doi.org/10.1016/j.jtct.2021.11.013

Graft-versus-Host Disease Prophylaxis with Post-Transplantation Cyclophosphamide versus Cyclosporine A and Methotrexate in Matched Sibling Donor Transplantation. / Nagler, Arnon; Labopin, Myriam; Dholaria, Bhagirathbhai et al.
In: Transplantation and Cellular Therapy, Vol. 28, No. 2, 02.2022, p. 86.e1-86.e8.

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

TY - JOUR

T1 - Graft-versus-Host Disease Prophylaxis with Post-Transplantation Cyclophosphamide versus Cyclosporine A and Methotrexate in Matched Sibling Donor Transplantation

AU - Nagler, Arnon

AU - Labopin, Myriam

AU - Dholaria, Bhagirathbhai

AU - Wu, Depei

AU - Choi, Goda

AU - Aljurf, Mahmoud

AU - Ciceri, Fabio

AU - Gedde-Dahl, Tobias

AU - Meijer, Ellen

AU - Niittyvuopio, Riitta

AU - Bondarenko, Sergey

AU - Bourhis, Jean Henri

AU - Cornelissen, Jan J.

AU - Socié, Gerard

AU - Koc, Yener

AU - Canaani, Jonathan

AU - Savani, Bipin

AU - Bug, Gesine

AU - Spyridonidis, Alexandros

AU - Giebel, Sebastian

AU - Brissot, Eolia

AU - Bazarbachi, Ali

AU - Esteve, Jordi

AU - Mohty, Mohamad

N1 - Funding Information: The authors thank the EBMT centers and national registries for contributing patient information and data collection. Supporting information is available at the EBMT website ( www.ebmt.org). Reporting institutions included in this study are available in the Online Supporting Information Appendix. There is no relevant funding to report. A.N. M.M. and M.L. contributed to the conception and design of the study; M.L. analyzed the data; B.D. B.N.S. A.N. M.L. M.M. contributed to the writing of the manuscript; all authors critically reviewed the manuscript and approved the final version. A.N. and B.D. contributed equally to this work and should be considered co-first authors. Requests for the raw data used in this study should be addressed to M.L. Publisher Copyright: © 2021 The American Society for Transplantation and Cellular Therapy

PY - 2022/2

Y1 - 2022/2

N2 - Cyclosporine A (CSA) and methotrexate (MTX) is the standard graft-versus-host disease (GVHD) prophylaxis regimen for matched sibling donor (MSD) allogeneic hematopoietic cell transplantation (allo-HCT). Recently, post-transplantation cyclophosphamide (PTCy) has been shown to be effective in GVHD prevention. In this registry-based study, we compared outcomes of 118 patients treated with PTCy and 1202 patients with CSA/MTX who underwent MSD allo-HCT for acute myelogenous leukemia. In a matched-pair analysis, PTCy was associated with a higher incidence of relapse at 2 years compared with CSA/MTX (41.1% versus 21.3%; P =.039). The incidences of day +180 grade II-IV acute GVHD and 2-year chronic GVHD were comparable in the PTCy and CSA/MTX arms (25.2% versus 25.4% [P =.90] and 42.6% versus 42.6% [P =.84], respectively). Similarly, 2-year leukemia-free survival (LFS; 54.4% versus 74.32%; P =.052), overall survival (OS; 70.6% versus 79.7%; P =.15), and GVHD-free relapse-free survival (GRFS; 38.1% versus 52.5%; P =.49) were not statistically different in the 2 arms. Our data show that GVHD prophylaxis with PTCy is feasible, resulting in similar incidences of GVHD, GRFS, LFS, and OS as seen with conventional CSA/MTX in patients undergoing allo-HCT from an MSD. The higher rate of relapse observed with PTCy needs further evaluation in a prospective study.

AB - Cyclosporine A (CSA) and methotrexate (MTX) is the standard graft-versus-host disease (GVHD) prophylaxis regimen for matched sibling donor (MSD) allogeneic hematopoietic cell transplantation (allo-HCT). Recently, post-transplantation cyclophosphamide (PTCy) has been shown to be effective in GVHD prevention. In this registry-based study, we compared outcomes of 118 patients treated with PTCy and 1202 patients with CSA/MTX who underwent MSD allo-HCT for acute myelogenous leukemia. In a matched-pair analysis, PTCy was associated with a higher incidence of relapse at 2 years compared with CSA/MTX (41.1% versus 21.3%; P =.039). The incidences of day +180 grade II-IV acute GVHD and 2-year chronic GVHD were comparable in the PTCy and CSA/MTX arms (25.2% versus 25.4% [P =.90] and 42.6% versus 42.6% [P =.84], respectively). Similarly, 2-year leukemia-free survival (LFS; 54.4% versus 74.32%; P =.052), overall survival (OS; 70.6% versus 79.7%; P =.15), and GVHD-free relapse-free survival (GRFS; 38.1% versus 52.5%; P =.49) were not statistically different in the 2 arms. Our data show that GVHD prophylaxis with PTCy is feasible, resulting in similar incidences of GVHD, GRFS, LFS, and OS as seen with conventional CSA/MTX in patients undergoing allo-HCT from an MSD. The higher rate of relapse observed with PTCy needs further evaluation in a prospective study.

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U2 - 10.1016/j.jtct.2021.11.013

DO - 10.1016/j.jtct.2021.11.013

M3 - Article

C2 - 34856420

AN - SCOPUS:85121903982

SN - 2666-6367

VL - 28

SP - 86.e1-86.e8

JO - Transplantation and Cellular Therapy

JF - Transplantation and Cellular Therapy

IS - 2

ER -

Graft-versus-Host Disease Prophylaxis with Post-Transplantation Cyclophosphamide versus Cyclosporine A and Methotrexate in Matched Sibling Donor Transplantation

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