Inferior Outcomes with Cyclosporine and Mycophenolate Mofetil after Myeloablative Allogeneic Hematopoietic Cell Transplantation

Betty K. Hamilton, Ying Liu, Michael T. Hemmer, Navneet Majhail, Olle Ringden, Dennis Kim, Luciano Costa, Robert Stuart, Amin Alousi, Joseph A. Pidala, Daniel R. Couriel, Mahmoud Aljurf, Joseph H. Antin, Christopher Bredeson, Jean Yves Cahn, Mitchell Cairo, Sung Won Choi, Christopher Dandoy, Robert Peter Gale, Usama GergisPeiman Hematti, Yoshihiro Inamoto, Rammurti T. Kamble, Margaret MacMillan, David I. Marks, Eneida Nemecek, Taiga Nishihori, Ayman Saad, Bipin N. Savani, Jeff Schriber, Sachiko Seo, Gérard Socié, Takanori Teshima, Leo F. Verdonck, Edmund K. Waller, Mona Wirk, Stephen R. Spellman, Mukta Arora, Saurabh Chhabra

Research output: Contribution to journalArticle

Abstract

Combination therapy with a calcineurin inhibitor (CNI), such as cyclosporine (CSA) or tacrolimus (Tac), and methotrexate (MTX) or mycophenolate mofetil (MMF) is a widely used approach to graft-versus-host disease (GVHD) prevention. Data on the comparative effectiveness of MMF compared with MTX are limited and conflicting, however. We analyzed data from the Center for International Blood and Marrow Transplant Research for adult patients undergoing first myeloablative hematopoietic cell transplantation (HCT) from an HLA-identical matched related donor (MRD; n = 3979) or matched unrelated donor (URD; n = 4163) using CSA+MMF, CSA+MTX, Tac+MMF, or Tac+MTX for GVHD prevention between 2000 and 2013. Within the MRD cohort, 2252 patients received CSA+MTX, 1391 received Tac+MTX, 114 received CSA+MMF, and 222 received Tac+MMF. Recipients of CSA+MMF had a higher incidence of acute GVHD grade II-IV (hazard ratio [HR], 1.65; 95% confidence interval [CI], 1.24 to 2.20; P < .001) and grade III-IV (HR, 1.92; 95% CI, 1.31 to 2.83; P < .001) compared with Tac+MTX. The use of CSA+MMF was also associated with inferior overall survival (OS) (HR, 2.31; 95% CI, 1.73 to 3.09; P < .001) due to higher transplantation-related mortality (TRM) (HR, 4.03; 95% CI, 2.61 to 6.23; P < .001) compared with Tac+MTX. Within the URD cohort, 974 patients received CSA+MTX, 2697 received Tac+MTX, 68 received CSA+MMF, and 424 received Tac+MMF. CSA+MMF was again significantly associated with a higher incidence of grade III-IV acute GVHD (HR, 2.31; 95% CI, 1.57 to 3.42; P <0001), worse OS (HR, 2.36; 95% CI, 1.67 to 3.35; P < .001), and higher TRM (HR, 3.09; 95% CI, 2.00 to 4.77; P < .001), compared with Tac+MTX and other regimens. Thus, this large retrospective comparison of MMF versus MTX in combination with CSA or Tac demonstrates significantly worse GVHD and survival outcomes with CSA+MMF compared with Tac+MTX.

Original languageEnglish (US)
Pages (from-to)1744-1755
Number of pages12
JournalBiology of Blood and Marrow Transplantation
Volume25
Issue number9
DOIs
StatePublished - Sep 2019

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Mycophenolic Acid
Cell Transplantation
Tacrolimus
Methotrexate
Cyclosporine
Graft vs Host Disease
Confidence Intervals
Survival
Transplantation
Unrelated Donors
Mortality
Incidence

All Science Journal Classification (ASJC) codes

  • Hematology
  • Transplantation

Cite this

Hamilton, Betty K. ; Liu, Ying ; Hemmer, Michael T. ; Majhail, Navneet ; Ringden, Olle ; Kim, Dennis ; Costa, Luciano ; Stuart, Robert ; Alousi, Amin ; Pidala, Joseph A. ; Couriel, Daniel R. ; Aljurf, Mahmoud ; Antin, Joseph H. ; Bredeson, Christopher ; Cahn, Jean Yves ; Cairo, Mitchell ; Choi, Sung Won ; Dandoy, Christopher ; Gale, Robert Peter ; Gergis, Usama ; Hematti, Peiman ; Inamoto, Yoshihiro ; Kamble, Rammurti T. ; MacMillan, Margaret ; Marks, David I. ; Nemecek, Eneida ; Nishihori, Taiga ; Saad, Ayman ; Savani, Bipin N. ; Schriber, Jeff ; Seo, Sachiko ; Socié, Gérard ; Teshima, Takanori ; Verdonck, Leo F. ; Waller, Edmund K. ; Wirk, Mona ; Spellman, Stephen R. ; Arora, Mukta ; Chhabra, Saurabh. / Inferior Outcomes with Cyclosporine and Mycophenolate Mofetil after Myeloablative Allogeneic Hematopoietic Cell Transplantation. In: Biology of Blood and Marrow Transplantation. 2019 ; Vol. 25, No. 9. pp. 1744-1755.
@article{c796374c6d174114a0ea5cafbdcad14a,
title = "Inferior Outcomes with Cyclosporine and Mycophenolate Mofetil after Myeloablative Allogeneic Hematopoietic Cell Transplantation",
abstract = "Combination therapy with a calcineurin inhibitor (CNI), such as cyclosporine (CSA) or tacrolimus (Tac), and methotrexate (MTX) or mycophenolate mofetil (MMF) is a widely used approach to graft-versus-host disease (GVHD) prevention. Data on the comparative effectiveness of MMF compared with MTX are limited and conflicting, however. We analyzed data from the Center for International Blood and Marrow Transplant Research for adult patients undergoing first myeloablative hematopoietic cell transplantation (HCT) from an HLA-identical matched related donor (MRD; n = 3979) or matched unrelated donor (URD; n = 4163) using CSA+MMF, CSA+MTX, Tac+MMF, or Tac+MTX for GVHD prevention between 2000 and 2013. Within the MRD cohort, 2252 patients received CSA+MTX, 1391 received Tac+MTX, 114 received CSA+MMF, and 222 received Tac+MMF. Recipients of CSA+MMF had a higher incidence of acute GVHD grade II-IV (hazard ratio [HR], 1.65; 95{\%} confidence interval [CI], 1.24 to 2.20; P < .001) and grade III-IV (HR, 1.92; 95{\%} CI, 1.31 to 2.83; P < .001) compared with Tac+MTX. The use of CSA+MMF was also associated with inferior overall survival (OS) (HR, 2.31; 95{\%} CI, 1.73 to 3.09; P < .001) due to higher transplantation-related mortality (TRM) (HR, 4.03; 95{\%} CI, 2.61 to 6.23; P < .001) compared with Tac+MTX. Within the URD cohort, 974 patients received CSA+MTX, 2697 received Tac+MTX, 68 received CSA+MMF, and 424 received Tac+MMF. CSA+MMF was again significantly associated with a higher incidence of grade III-IV acute GVHD (HR, 2.31; 95{\%} CI, 1.57 to 3.42; P <0001), worse OS (HR, 2.36; 95{\%} CI, 1.67 to 3.35; P < .001), and higher TRM (HR, 3.09; 95{\%} CI, 2.00 to 4.77; P < .001), compared with Tac+MTX and other regimens. Thus, this large retrospective comparison of MMF versus MTX in combination with CSA or Tac demonstrates significantly worse GVHD and survival outcomes with CSA+MMF compared with Tac+MTX.",
author = "Hamilton, {Betty K.} and Ying Liu and Hemmer, {Michael T.} and Navneet Majhail and Olle Ringden and Dennis Kim and Luciano Costa and Robert Stuart and Amin Alousi and Pidala, {Joseph A.} and Couriel, {Daniel R.} and Mahmoud Aljurf and Antin, {Joseph H.} and Christopher Bredeson and Cahn, {Jean Yves} and Mitchell Cairo and Choi, {Sung Won} and Christopher Dandoy and Gale, {Robert Peter} and Usama Gergis and Peiman Hematti and Yoshihiro Inamoto and Kamble, {Rammurti T.} and Margaret MacMillan and Marks, {David I.} and Eneida Nemecek and Taiga Nishihori and Ayman Saad and Savani, {Bipin N.} and Jeff Schriber and Sachiko Seo and G{\'e}rard Soci{\'e} and Takanori Teshima and Verdonck, {Leo F.} and Waller, {Edmund K.} and Mona Wirk and Spellman, {Stephen R.} and Mukta Arora and Saurabh Chhabra",
year = "2019",
month = "9",
doi = "10.1016/j.bbmt.2019.05.019",
language = "English (US)",
volume = "25",
pages = "1744--1755",
journal = "Biology of Blood and Marrow Transplantation",
issn = "1083-8791",
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Hamilton, BK, Liu, Y, Hemmer, MT, Majhail, N, Ringden, O, Kim, D, Costa, L, Stuart, R, Alousi, A, Pidala, JA, Couriel, DR, Aljurf, M, Antin, JH, Bredeson, C, Cahn, JY, Cairo, M, Choi, SW, Dandoy, C, Gale, RP, Gergis, U, Hematti, P, Inamoto, Y, Kamble, RT, MacMillan, M, Marks, DI, Nemecek, E, Nishihori, T, Saad, A, Savani, BN, Schriber, J, Seo, S, Socié, G, Teshima, T, Verdonck, LF, Waller, EK, Wirk, M, Spellman, SR, Arora, M & Chhabra, S 2019, 'Inferior Outcomes with Cyclosporine and Mycophenolate Mofetil after Myeloablative Allogeneic Hematopoietic Cell Transplantation', Biology of Blood and Marrow Transplantation, vol. 25, no. 9, pp. 1744-1755. https://doi.org/10.1016/j.bbmt.2019.05.019

Inferior Outcomes with Cyclosporine and Mycophenolate Mofetil after Myeloablative Allogeneic Hematopoietic Cell Transplantation. / Hamilton, Betty K.; Liu, Ying; Hemmer, Michael T.; Majhail, Navneet; Ringden, Olle; Kim, Dennis; Costa, Luciano; Stuart, Robert; Alousi, Amin; Pidala, Joseph A.; Couriel, Daniel R.; Aljurf, Mahmoud; Antin, Joseph H.; Bredeson, Christopher; Cahn, Jean Yves; Cairo, Mitchell; Choi, Sung Won; Dandoy, Christopher; Gale, Robert Peter; Gergis, Usama; Hematti, Peiman; Inamoto, Yoshihiro; Kamble, Rammurti T.; MacMillan, Margaret; Marks, David I.; Nemecek, Eneida; Nishihori, Taiga; Saad, Ayman; Savani, Bipin N.; Schriber, Jeff; Seo, Sachiko; Socié, Gérard; Teshima, Takanori; Verdonck, Leo F.; Waller, Edmund K.; Wirk, Mona; Spellman, Stephen R.; Arora, Mukta; Chhabra, Saurabh.

In: Biology of Blood and Marrow Transplantation, Vol. 25, No. 9, 09.2019, p. 1744-1755.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Inferior Outcomes with Cyclosporine and Mycophenolate Mofetil after Myeloablative Allogeneic Hematopoietic Cell Transplantation

AU - Hamilton, Betty K.

AU - Liu, Ying

AU - Hemmer, Michael T.

AU - Majhail, Navneet

AU - Ringden, Olle

AU - Kim, Dennis

AU - Costa, Luciano

AU - Stuart, Robert

AU - Alousi, Amin

AU - Pidala, Joseph A.

AU - Couriel, Daniel R.

AU - Aljurf, Mahmoud

AU - Antin, Joseph H.

AU - Bredeson, Christopher

AU - Cahn, Jean Yves

AU - Cairo, Mitchell

AU - Choi, Sung Won

AU - Dandoy, Christopher

AU - Gale, Robert Peter

AU - Gergis, Usama

AU - Hematti, Peiman

AU - Inamoto, Yoshihiro

AU - Kamble, Rammurti T.

AU - MacMillan, Margaret

AU - Marks, David I.

AU - Nemecek, Eneida

AU - Nishihori, Taiga

AU - Saad, Ayman

AU - Savani, Bipin N.

AU - Schriber, Jeff

AU - Seo, Sachiko

AU - Socié, Gérard

AU - Teshima, Takanori

AU - Verdonck, Leo F.

AU - Waller, Edmund K.

AU - Wirk, Mona

AU - Spellman, Stephen R.

AU - Arora, Mukta

AU - Chhabra, Saurabh

PY - 2019/9

Y1 - 2019/9

N2 - Combination therapy with a calcineurin inhibitor (CNI), such as cyclosporine (CSA) or tacrolimus (Tac), and methotrexate (MTX) or mycophenolate mofetil (MMF) is a widely used approach to graft-versus-host disease (GVHD) prevention. Data on the comparative effectiveness of MMF compared with MTX are limited and conflicting, however. We analyzed data from the Center for International Blood and Marrow Transplant Research for adult patients undergoing first myeloablative hematopoietic cell transplantation (HCT) from an HLA-identical matched related donor (MRD; n = 3979) or matched unrelated donor (URD; n = 4163) using CSA+MMF, CSA+MTX, Tac+MMF, or Tac+MTX for GVHD prevention between 2000 and 2013. Within the MRD cohort, 2252 patients received CSA+MTX, 1391 received Tac+MTX, 114 received CSA+MMF, and 222 received Tac+MMF. Recipients of CSA+MMF had a higher incidence of acute GVHD grade II-IV (hazard ratio [HR], 1.65; 95% confidence interval [CI], 1.24 to 2.20; P < .001) and grade III-IV (HR, 1.92; 95% CI, 1.31 to 2.83; P < .001) compared with Tac+MTX. The use of CSA+MMF was also associated with inferior overall survival (OS) (HR, 2.31; 95% CI, 1.73 to 3.09; P < .001) due to higher transplantation-related mortality (TRM) (HR, 4.03; 95% CI, 2.61 to 6.23; P < .001) compared with Tac+MTX. Within the URD cohort, 974 patients received CSA+MTX, 2697 received Tac+MTX, 68 received CSA+MMF, and 424 received Tac+MMF. CSA+MMF was again significantly associated with a higher incidence of grade III-IV acute GVHD (HR, 2.31; 95% CI, 1.57 to 3.42; P <0001), worse OS (HR, 2.36; 95% CI, 1.67 to 3.35; P < .001), and higher TRM (HR, 3.09; 95% CI, 2.00 to 4.77; P < .001), compared with Tac+MTX and other regimens. Thus, this large retrospective comparison of MMF versus MTX in combination with CSA or Tac demonstrates significantly worse GVHD and survival outcomes with CSA+MMF compared with Tac+MTX.

AB - Combination therapy with a calcineurin inhibitor (CNI), such as cyclosporine (CSA) or tacrolimus (Tac), and methotrexate (MTX) or mycophenolate mofetil (MMF) is a widely used approach to graft-versus-host disease (GVHD) prevention. Data on the comparative effectiveness of MMF compared with MTX are limited and conflicting, however. We analyzed data from the Center for International Blood and Marrow Transplant Research for adult patients undergoing first myeloablative hematopoietic cell transplantation (HCT) from an HLA-identical matched related donor (MRD; n = 3979) or matched unrelated donor (URD; n = 4163) using CSA+MMF, CSA+MTX, Tac+MMF, or Tac+MTX for GVHD prevention between 2000 and 2013. Within the MRD cohort, 2252 patients received CSA+MTX, 1391 received Tac+MTX, 114 received CSA+MMF, and 222 received Tac+MMF. Recipients of CSA+MMF had a higher incidence of acute GVHD grade II-IV (hazard ratio [HR], 1.65; 95% confidence interval [CI], 1.24 to 2.20; P < .001) and grade III-IV (HR, 1.92; 95% CI, 1.31 to 2.83; P < .001) compared with Tac+MTX. The use of CSA+MMF was also associated with inferior overall survival (OS) (HR, 2.31; 95% CI, 1.73 to 3.09; P < .001) due to higher transplantation-related mortality (TRM) (HR, 4.03; 95% CI, 2.61 to 6.23; P < .001) compared with Tac+MTX. Within the URD cohort, 974 patients received CSA+MTX, 2697 received Tac+MTX, 68 received CSA+MMF, and 424 received Tac+MMF. CSA+MMF was again significantly associated with a higher incidence of grade III-IV acute GVHD (HR, 2.31; 95% CI, 1.57 to 3.42; P <0001), worse OS (HR, 2.36; 95% CI, 1.67 to 3.35; P < .001), and higher TRM (HR, 3.09; 95% CI, 2.00 to 4.77; P < .001), compared with Tac+MTX and other regimens. Thus, this large retrospective comparison of MMF versus MTX in combination with CSA or Tac demonstrates significantly worse GVHD and survival outcomes with CSA+MMF compared with Tac+MTX.

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