Faculty Collaboration Database

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. Biol Blood Marrow Transplant 2019 Jan;25(1):73-85

Date

08/29/2018

Pubmed ID

30153491

Pubmed Central ID

PMC6355336

DOI

10.1016/j.bbmt.2018.08.018

Scopus ID

2-s2.0-85054156982 (requires institutional sign-in at Scopus site)   32 Citations

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.

Author List

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 J, 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

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

Adult
Aged
Allografts
Calcineurin Inhibitors
Disease-Free Survival
Female
Graft vs Host Disease
Hematopoietic Stem Cell Transplantation
Humans
Leukemia
Male
Methotrexate
Middle Aged
Mycophenolic Acid
Myelodysplastic Syndromes
Retrospective Studies
Siblings
Survival Rate
Tacrolimus
Transplantation Conditioning