Faculty Collaboration Database

Inferior Outcomes with Cyclosporine and Mycophenolate Mofetil after Myeloablative Allogeneic Hematopoietic Cell Transplantation. Biol Blood Marrow Transplant 2019 Sep;25(9):1744-1755

Date

06/04/2019

Pubmed ID

31158502

Pubmed Central ID

PMC7039394

DOI

10.1016/j.bbmt.2019.05.019

Scopus ID

2-s2.0-85068515130 (requires institutional sign-in at Scopus site)   9 Citations

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 List

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

Author

Peiman Hematti MD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Aged
Allografts
Cyclosporine
Disease-Free Survival
Female
Graft vs Host Disease
Hematopoietic Stem Cell Transplantation
Humans
Male
Middle Aged
Mycophenolic Acid
Survival Rate