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
N1 - Publisher Copyright:
© 2019
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.
KW - Allogeneic hematopoietic cell transplantation
KW - Graft-versus-host disease
KW - Methotrexate
KW - Mycophenolate mofetil
KW - Myeloablative
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UR - http://www.scopus.com/inward/citedby.url?scp=85068515130&partnerID=8YFLogxK
U2 - 10.1016/j.bbmt.2019.05.019
DO - 10.1016/j.bbmt.2019.05.019
M3 - Article
C2 - 31158502
AN - SCOPUS:85068515130
SN - 1083-8791
VL - 25
SP - 1744
EP - 1755
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 9
ER -