Comparative Analysis of Calcineurin Inhibitor–Based Methotrexate and Mycophenolate Mofetil–Containing Regimens for Prevention of Graft-versus-Host Disease after Reduced-Intensity Conditioning Allogeneic Transplantation

Saurabh Chhabra, Ying Liu, Michael T. Hemmer, Luciano Costa, Joseph A. Pidala, Daniel R. Couriel, Amin M. Alousi, Navneet S. Majhail, Robert K. Stuart, Dennis Kim, Olle Ringden, Alvaro Urbano-Ispizua, Ayman Saad, Bipin N. Savani, Brenda Cooper, David I. Marks, Gerard Socie, Harry C. Schouten, Helene Schoemans, Hisham Abdel-Azim & 26 others Jean Yared, Jean Yves Cahn, John E Wagner, Joseph H. Antin, Leo F. Verdonck, Leslie Lehmann, Mahmoud D. Aljurf, Margaret L MacMillan, Mark R. Litzow, Melhem M. Solh, Muna Qayed, Peiman Hematti, Rammurti T. Kamble, Ravi Vij, Robert J. Hayashi, Robert P. Gale, Rodrigo Martino, Sachiko Seo, Shahrukh K. Hashmi, Taiga Nishihori, Takanori Teshima, Usama Gergis, Yoshihiro Inamoto, Stephen R. Spellman, Mukta Arora, Betty K. Hamilton

Research output: Contribution to journalArticle

Abstract

The combination of a calcineurin inhibitor (CNI) such as tacrolimus (TAC) or cyclosporine (CYSP) with methotrexate (MTX) or with mycophenolate mofetil (MMF) has been commonly used for graft-versus-host disease (GVHD) prophylaxis after reduced-intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (alloHCT), but there are limited data comparing efficacy of the 2 regimens. We evaluated 1564 adult patients who underwent RIC alloHCT for acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL), chronic myelogenous leukemia (CML), and myelodysplastic syndrome (MDS) from 2000 to 2013 using HLA-identical sibling (matched related donor [MRD]) or unrelated donor (URD) peripheral blood graft and received CYSP or TAC with MTX or MMF for GVHD prophylaxis. Primary outcomes of the study were acute and chronic GVHD and overall survival (OS). The study divided the patient population into 4 cohorts based on regimen: MMF-TAC, MMF-CYSP, MTX-TAC, and MTX-CYSP. In the URD group, MMF-CYSP was associated with increased risk of grade II to IV acute GVHD (relative risk [RR], 1.78; P <.001) and grade III to IV acute GVHD (RR, 1.93; P =.006) compared with MTX-TAC. In the URD group, use of MMF-TAC (versus MTX-TAC) lead to higher nonrelapse mortality. (hazard ratio, 1.48; P =.008). In either group, no there was no difference in chronic GVHD, disease-free survival, and OS among the GVHD prophylaxis regimens. For RIC alloHCT using MRD, there are no differences in outcomes based on GVHD prophylaxis. However, with URD RIC alloHCT, MMF-CYSP was inferior to MTX-based regimens for acute GVHD prevention, but all the regimens were equivalent in terms of chronic GVHD and OS. Prospective studies, targeting URD recipients are needed to confirm these results.

Original languageEnglish (US)
Pages (from-to)73-85
Number of pages13
JournalBiology of Blood and Marrow Transplantation
Volume25
Issue number1
DOIs
StatePublished - Jan 1 2019

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Calcineurin
Homologous Transplantation
Graft vs Host Disease
Methotrexate
Mycophenolic Acid
Tacrolimus
Unrelated Donors
Cyclosporine
Cell Transplantation
Survival
Conditioning (Psychology)
Tissue Donors
Myelodysplastic Syndromes
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Acute Myeloid Leukemia
Disease-Free Survival
Siblings
Outcome Assessment (Health Care)
Prospective Studies

Keywords

  • Allogeneic hematopoietic cell transplantation
  • Calcineurin inhibitor Tacrolimus
  • Cyclosporine
  • Graft-versus-host disease prophylaxis
  • Methotrexate
  • Mycophenolate mofetil
  • Reduced-intensity conditioning

Cite this

Comparative Analysis of Calcineurin Inhibitor–Based Methotrexate and Mycophenolate Mofetil–Containing Regimens for Prevention of Graft-versus-Host Disease after Reduced-Intensity Conditioning Allogeneic Transplantation. / Chhabra, Saurabh; Liu, Ying; Hemmer, Michael T.; Costa, Luciano; Pidala, Joseph A.; Couriel, Daniel R.; Alousi, Amin M.; Majhail, Navneet S.; Stuart, Robert K.; Kim, Dennis; Ringden, Olle; Urbano-Ispizua, Alvaro; Saad, Ayman; Savani, Bipin N.; Cooper, Brenda; Marks, David I.; Socie, Gerard; Schouten, Harry C.; Schoemans, Helene; Abdel-Azim, Hisham; Yared, Jean; Cahn, Jean Yves; Wagner, John E; Antin, Joseph H.; Verdonck, Leo F.; Lehmann, Leslie; Aljurf, Mahmoud D.; MacMillan, Margaret L; Litzow, Mark R.; Solh, Melhem M.; Qayed, Muna; Hematti, Peiman; Kamble, Rammurti T.; Vij, Ravi; Hayashi, Robert J.; Gale, Robert P.; Martino, Rodrigo; Seo, Sachiko; Hashmi, Shahrukh K.; Nishihori, Taiga; Teshima, Takanori; Gergis, Usama; Inamoto, Yoshihiro; Spellman, Stephen R.; Arora, Mukta; Hamilton, Betty K.

In: Biology of Blood and Marrow Transplantation, Vol. 25, No. 1, 01.01.2019, p. 73-85.

Research output: Contribution to journalArticle

Chhabra, S, Liu, Y, Hemmer, MT, Costa, L, Pidala, JA, Couriel, DR, Alousi, AM, Majhail, NS, Stuart, RK, Kim, D, Ringden, O, Urbano-Ispizua, A, Saad, A, Savani, BN, Cooper, B, Marks, DI, Socie, G, Schouten, HC, Schoemans, H, Abdel-Azim, H, Yared, J, Cahn, JY, Wagner, JE, Antin, JH, Verdonck, LF, Lehmann, L, Aljurf, MD, MacMillan, ML, Litzow, MR, Solh, MM, Qayed, M, Hematti, P, Kamble, RT, Vij, R, Hayashi, RJ, Gale, RP, Martino, R, Seo, S, Hashmi, SK, Nishihori, T, Teshima, T, Gergis, U, Inamoto, Y, Spellman, SR, Arora, M & Hamilton, BK 2019, 'Comparative Analysis of Calcineurin Inhibitor–Based Methotrexate and Mycophenolate Mofetil–Containing Regimens for Prevention of Graft-versus-Host Disease after Reduced-Intensity Conditioning Allogeneic Transplantation', Biology of Blood and Marrow Transplantation, vol. 25, no. 1, pp. 73-85. https://doi.org/10.1016/j.bbmt.2018.08.018
Chhabra, Saurabh ; Liu, Ying ; Hemmer, Michael T. ; Costa, Luciano ; Pidala, Joseph A. ; Couriel, Daniel R. ; Alousi, Amin M. ; Majhail, Navneet S. ; Stuart, Robert K. ; Kim, Dennis ; Ringden, Olle ; Urbano-Ispizua, Alvaro ; Saad, Ayman ; Savani, Bipin N. ; Cooper, Brenda ; Marks, David I. ; Socie, Gerard ; Schouten, Harry C. ; Schoemans, Helene ; Abdel-Azim, Hisham ; Yared, Jean ; Cahn, Jean Yves ; Wagner, John E ; Antin, Joseph H. ; Verdonck, Leo F. ; Lehmann, Leslie ; Aljurf, Mahmoud D. ; MacMillan, Margaret L ; Litzow, Mark R. ; Solh, Melhem M. ; Qayed, Muna ; Hematti, Peiman ; Kamble, Rammurti T. ; Vij, Ravi ; Hayashi, Robert J. ; Gale, Robert P. ; Martino, Rodrigo ; Seo, Sachiko ; Hashmi, Shahrukh K. ; Nishihori, Taiga ; Teshima, Takanori ; Gergis, Usama ; Inamoto, Yoshihiro ; Spellman, Stephen R. ; Arora, Mukta ; Hamilton, Betty K. / Comparative Analysis of Calcineurin Inhibitor–Based Methotrexate and Mycophenolate Mofetil–Containing Regimens for Prevention of Graft-versus-Host Disease after Reduced-Intensity Conditioning Allogeneic Transplantation. In: Biology of Blood and Marrow Transplantation. 2019 ; Vol. 25, No. 1. pp. 73-85.
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abstract = "The combination of a calcineurin inhibitor (CNI) such as tacrolimus (TAC) or cyclosporine (CYSP) with methotrexate (MTX) or with mycophenolate mofetil (MMF) has been commonly used for graft-versus-host disease (GVHD) prophylaxis after reduced-intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (alloHCT), but there are limited data comparing efficacy of the 2 regimens. We evaluated 1564 adult patients who underwent RIC alloHCT for acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL), chronic myelogenous leukemia (CML), and myelodysplastic syndrome (MDS) from 2000 to 2013 using HLA-identical sibling (matched related donor [MRD]) or unrelated donor (URD) peripheral blood graft and received CYSP or TAC with MTX or MMF for GVHD prophylaxis. Primary outcomes of the study were acute and chronic GVHD and overall survival (OS). The study divided the patient population into 4 cohorts based on regimen: MMF-TAC, MMF-CYSP, MTX-TAC, and MTX-CYSP. In the URD group, MMF-CYSP was associated with increased risk of grade II to IV acute GVHD (relative risk [RR], 1.78; P <.001) and grade III to IV acute GVHD (RR, 1.93; P =.006) compared with MTX-TAC. In the URD group, use of MMF-TAC (versus MTX-TAC) lead to higher nonrelapse mortality. (hazard ratio, 1.48; P =.008). In either group, no there was no difference in chronic GVHD, disease-free survival, and OS among the GVHD prophylaxis regimens. For RIC alloHCT using MRD, there are no differences in outcomes based on GVHD prophylaxis. However, with URD RIC alloHCT, MMF-CYSP was inferior to MTX-based regimens for acute GVHD prevention, but all the regimens were equivalent in terms of chronic GVHD and OS. Prospective studies, targeting URD recipients are needed to confirm these results.",
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T1 - Comparative Analysis of Calcineurin Inhibitor–Based Methotrexate and Mycophenolate Mofetil–Containing Regimens for Prevention of Graft-versus-Host Disease after Reduced-Intensity Conditioning Allogeneic Transplantation

AU - Chhabra, Saurabh

AU - Liu, Ying

AU - Hemmer, Michael T.

AU - Costa, Luciano

AU - Pidala, Joseph A.

AU - Couriel, Daniel R.

AU - Alousi, Amin M.

AU - Majhail, Navneet S.

AU - Stuart, Robert K.

AU - Kim, Dennis

AU - Ringden, Olle

AU - Urbano-Ispizua, Alvaro

AU - Saad, Ayman

AU - Savani, Bipin N.

AU - Cooper, Brenda

AU - Marks, David I.

AU - Socie, Gerard

AU - Schouten, Harry C.

AU - Schoemans, Helene

AU - Abdel-Azim, Hisham

AU - Yared, Jean

AU - Cahn, Jean Yves

AU - Wagner, John E

AU - Antin, Joseph H.

AU - Verdonck, Leo F.

AU - Lehmann, Leslie

AU - Aljurf, Mahmoud D.

AU - MacMillan, Margaret L

AU - Litzow, Mark R.

AU - Solh, Melhem M.

AU - Qayed, Muna

AU - Hematti, Peiman

AU - Kamble, Rammurti T.

AU - Vij, Ravi

AU - Hayashi, Robert J.

AU - Gale, Robert P.

AU - Martino, Rodrigo

AU - Seo, Sachiko

AU - Hashmi, Shahrukh K.

AU - Nishihori, Taiga

AU - Teshima, Takanori

AU - Gergis, Usama

AU - Inamoto, Yoshihiro

AU - Spellman, Stephen R.

AU - Arora, Mukta

AU - Hamilton, Betty K.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - The combination of a calcineurin inhibitor (CNI) such as tacrolimus (TAC) or cyclosporine (CYSP) with methotrexate (MTX) or with mycophenolate mofetil (MMF) has been commonly used for graft-versus-host disease (GVHD) prophylaxis after reduced-intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (alloHCT), but there are limited data comparing efficacy of the 2 regimens. We evaluated 1564 adult patients who underwent RIC alloHCT for acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL), chronic myelogenous leukemia (CML), and myelodysplastic syndrome (MDS) from 2000 to 2013 using HLA-identical sibling (matched related donor [MRD]) or unrelated donor (URD) peripheral blood graft and received CYSP or TAC with MTX or MMF for GVHD prophylaxis. Primary outcomes of the study were acute and chronic GVHD and overall survival (OS). The study divided the patient population into 4 cohorts based on regimen: MMF-TAC, MMF-CYSP, MTX-TAC, and MTX-CYSP. In the URD group, MMF-CYSP was associated with increased risk of grade II to IV acute GVHD (relative risk [RR], 1.78; P <.001) and grade III to IV acute GVHD (RR, 1.93; P =.006) compared with MTX-TAC. In the URD group, use of MMF-TAC (versus MTX-TAC) lead to higher nonrelapse mortality. (hazard ratio, 1.48; P =.008). In either group, no there was no difference in chronic GVHD, disease-free survival, and OS among the GVHD prophylaxis regimens. For RIC alloHCT using MRD, there are no differences in outcomes based on GVHD prophylaxis. However, with URD RIC alloHCT, MMF-CYSP was inferior to MTX-based regimens for acute GVHD prevention, but all the regimens were equivalent in terms of chronic GVHD and OS. Prospective studies, targeting URD recipients are needed to confirm these results.

AB - The combination of a calcineurin inhibitor (CNI) such as tacrolimus (TAC) or cyclosporine (CYSP) with methotrexate (MTX) or with mycophenolate mofetil (MMF) has been commonly used for graft-versus-host disease (GVHD) prophylaxis after reduced-intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (alloHCT), but there are limited data comparing efficacy of the 2 regimens. We evaluated 1564 adult patients who underwent RIC alloHCT for acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL), chronic myelogenous leukemia (CML), and myelodysplastic syndrome (MDS) from 2000 to 2013 using HLA-identical sibling (matched related donor [MRD]) or unrelated donor (URD) peripheral blood graft and received CYSP or TAC with MTX or MMF for GVHD prophylaxis. Primary outcomes of the study were acute and chronic GVHD and overall survival (OS). The study divided the patient population into 4 cohorts based on regimen: MMF-TAC, MMF-CYSP, MTX-TAC, and MTX-CYSP. In the URD group, MMF-CYSP was associated with increased risk of grade II to IV acute GVHD (relative risk [RR], 1.78; P <.001) and grade III to IV acute GVHD (RR, 1.93; P =.006) compared with MTX-TAC. In the URD group, use of MMF-TAC (versus MTX-TAC) lead to higher nonrelapse mortality. (hazard ratio, 1.48; P =.008). In either group, no there was no difference in chronic GVHD, disease-free survival, and OS among the GVHD prophylaxis regimens. For RIC alloHCT using MRD, there are no differences in outcomes based on GVHD prophylaxis. However, with URD RIC alloHCT, MMF-CYSP was inferior to MTX-based regimens for acute GVHD prevention, but all the regimens were equivalent in terms of chronic GVHD and OS. Prospective studies, targeting URD recipients are needed to confirm these results.

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