Mycophenolate mofetil versus methotrexate for prevention of graft-versus-host disease in people receiving allogeneic hematopoietic stem cell transplantation

Kharfan‐Dabaja, Mohamed A.; Mhaskar, Rahul; Reljic, Tea; Pidala, Joseph; Perkins, Janelle; Djulbegoviĉ, Benjamin; Kumar, Amit

doi:10.1002/14651858.cd010280.pub2

Cited by 40 publications

(28 citation statements)

References 39 publications

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“…in conjunction with high-dose pre-transplant conditioning, the immunosuppressive regimen was safe, and provided effective GVHD-protection while not compromising control of underlying malignancy. if these findings are confirmed in future studies, HLA-matched mobilized blood cell transplantation may gain even greater acceptance and replace marrow as a source of stem cells for most indications (65).…”

Section: Prevention and Treatmentmentioning

confidence: 82%

Acute Graft Versus Host Disease: A Comprehensive Review

et al. 2017

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Section: Prevention and Treatmentmentioning

confidence: 82%

Acute Graft Versus Host Disease: A Comprehensive Review

et al. 2017

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“…However, the cumulative incidence of grade III-IV aGVHD was higher in the MMF arm (19% vs. 4%, p=0.03), predominantly in MAC alloHCT using URD. A meta-analysis of the above-mentioned three randomized trials by the Cochrane Collaboration found no differences in the rates of aGVHD and cGVHD between the different regimens 24 . There was no evidence for a significant difference between MMF and MTX for the incidence of aGVHD and cGVHD, neutrophil engraftment, incidence of relapse, NRM and OS.…”

Section: Discussionmentioning

confidence: 98%

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

Liu

Hemmer

et al. 2019

Biology of Blood and Marrow Transplantation

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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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“…This result was consistent with previous findings for BMT/PBSCT, in which the median days until engraftment was 4 days earlier in the MMF-containing group. [22][23][24][25][26] Based on the cytotoxic effects of MTX and smaller nucleated cell number transplanted in UCBT, an even larger difference may be expected in the median days until engraftment between BMT/PBSCT and UCBT. However, we only observed a small difference, which may have been due to the different graft compositions between BMT/PBSCT and UCBT such as stem cell, T cells and other accessory cells.…”

Section: Discussionmentioning

confidence: 99%

“…20,21 Several prospective studies and meta-analyses have shown that MMF is a reasonable substitute for MTX that achieves similar outcomes with potential reductions in toxicity after sibling or unrelated BMT/PBSCT. [22][23][24][25][26] However, MTX and MMF in UCBT have not yet been compared in detail. Therefore, to investigate the better combination of CNI and either MTX or MMF, we conducted the present study to compare CNI plus MTX and CNI plus MMF regimens.…”

Section: Introductionmentioning

confidence: 99%

Exploratory research for optimal GvHD prophylaxis after single unit CBT in adults: short-term methotrexate reduced the incidence of severe GvHD more than mycophenolate mofetil

Terakura

Wake

Inamoto³

et al. 2016

Bone Marrow Transplant

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In order to examine GvHD prophylaxis in umbilical cord blood transplantation (UCBT) in more detail, we compared transplant outcomes after UCBT for acute leukemia among GvHD prophylaxes using registry data. We selected patients transplanted with a calcineurin inhibitor and methotrexate (MTX)/mycophenolate mofetil (MMF) combination. A total of 1516 first myeloablative UCBT between 2000 and 2012 (Cyclosporine A (CyA) plus MTX, 824, Tacrolimus (Tac) plus MTX, 554, Tac plus MMF, 138) were included. With adjusted analyses, Tac plus MMF showed a significantly higher risk for grade II-IV and III-IV acute GvHD than CyA or Tac plus MTX. Although NRM was similar, Tac plus MMF showed a significantly lower risk of relapse than CyA or Tac plus MTX. A significant difference was observed in the risk of overall mortality (OM) between the MTX-containing group and MMF-containing group. In patients with standard-risk disease, there was no significant difference in the risk of OM in any GvHD prophylaxis. However, in patients with advanced-risk disease, Tac plus MMF showed a significantly lower risk of OM. Therefore, MTX-containing prophylaxis is preferred in UCBT for standard-risk disease, whereas MMF-containing prophylaxis is preferred for advanced-risk disease. A prospective study to identify optimal GvHD prophylaxis for UCBT is warranted.

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Mycophenolate mofetil versus methotrexate for prevention of graft-versus-host disease in people receiving allogeneic hematopoietic stem cell transplantation

Cited by 40 publications

References 39 publications

Acute Graft Versus Host Disease: A Comprehensive Review

Acute Graft Versus Host Disease: A Comprehensive Review

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

Exploratory research for optimal GvHD prophylaxis after single unit CBT in adults: short-term methotrexate reduced the incidence of severe GvHD more than mycophenolate mofetil

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