Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2014 Feb;49(2):248-53.
doi: 10.1038/bmt.2013.167. Epub 2013 Oct 28.

Acute GVHD prophylaxis with standard-dose, micro-dose or no MTX after fludarabine/melphalan conditioning

G L Chen  1 , Y Zhang  1 , T Hahn  1 , S Abrams  2 , M Ross  1 , H Liu  1 , P L McCarthy  1
Affiliations

Acute GVHD prophylaxis with standard-dose, micro-dose or no MTX after fludarabine/melphalan conditioning

G L Chen et al. Bone Marrow Transplant. 2014 Feb.

Abstract

MTX is a standard component of acute GVHD prophylaxis. However, its use can be limited by toxicity. On the basis of disease risk, we prospectively assigned 132 consecutive patients from January 2005 to February 2011 undergoing first allogeneic hematopoietic cell transplant after conditioning with fludarabine and melphalan to acute GVHD prophylaxis with tacrolimus/MTX (TAC/MTX, N=22), TAC/micro-dose MTX/mycophenolate mofetil (TAC/μMTX/MMF, N=78) or TAC/MMF (TAC/MMF, N=32), to optimize acute GVHD prevention and decrease mortality. The median (range) follow-up was 24 (0.8-60) months. The median patient ages (range) were 37 (23-63), 56 (20-68) and 54 (22-68) years (P<0.0001) for TAC/MTX, TAC/μMTX/MMF and TAC/MMF, respectively. The 100-day cumulative incidences of grade III-IV acute GVHD were 19, 23 and 49% (P=0.015), respectively. The cumulative incidences of severe chronic GVHD at 1 year were 38, 29 and 79% (P<0.001), respectively. Regimen-related toxicities were not significantly different among the three prophylaxis regimens. PFS and OS were equivalent between the TAC/MTX and TAC/μMTX/MMF arms despite significantly older patients in the latter arm, and both had superior PFS and OS than the TAC/MMF arm. Acute GVHD prophylaxis with TAC/μMTX/MMF is as effective as TAC/MTX and superior to TAC/MMF.

PubMed Disclaimer

Conflict of interest statement

CONFLICT OF INTEREST

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Cumulative incidences of grade III–IV acute GVHD for TAC/MTX, TAC/μMTX/MMF and TAC/MMF. TAC/MMF results in significantly greater incidence of grade III–IV acute GVHD than TAC/MTX or TAC/μMTX/MMF (a) Acute GVHD organ involvement is greater for TAC/MMF than TAC/MTX or TAC/μMTX/MMF in the gastrointestinal tract (b) but not liver (c) or skin (d) thick line—TAC/MTX, dashed line—TAC/μMTX/MMF, thin line—TAC/MMF. Abbreviations: μMTX = micro-dose MTX (7.5 mg/m2); MMF = mycophenolate mofetil; MTX = standard-dose MTX (30–40 mg/m2); TAC = tacrolimus.
Figure 2
Figure 2
Cumulative incidences of severe cGVHD. TAC/MMF results in significantly increased incidence of severe cGVHD than TAC/MTX or TAC/μMTX/MMF. Abbreviations: cGVHD = chronic GVHD; μMTX micro-dose MTX (7.5 mg/m2); MMF = mycophenolate mofetil; MTX = standard-dose MTX (30–40 mg/m2); TAC = tacrolimus.
Figure 3
Figure 3
OS and PFS. (a) TAC/μMTX/MMF results in significantly better OS than TAC/MMF. (b) There is a trend toward improved PFS for TAC/μMTX/MMF when compared to TAC/MMF. Abbreviations: μMTX = micro-dose MTX (7.5 mg/m2); MMF = mycophenolate mofetil; MTX = standard-dose MTX (30–40 mg/m2); TAC = tacrolimus.
See this image and copyright information in PMC

References

    1. Valcarcel D, Sierra J, Wang T, Kan F, Gupta V, Hale GA, et al. One-antigen mismatched related versus HLA-matched unrelated donor hematopoietic stem cell transplantation in adults with acute leukemia: Center for International Blood and Marrow Transplant Research results in the era of molecular HLA typing. Biol Blood Marrow Transplant. 2011;17:640–648. - PMC - PubMed
    1. Hahn T, McCarthy PL, Jr, Zhang MJ, Wang D, Arora M, Frangoul H, et al. Risk factors for acute graft-versus-host disease after human leukocyte antigen-identical sibling transplants for adults with leukemia. J Clin Oncol. 2008;26:5728–5734. - PMC - PubMed
    1. Ratanatharathorn V, Nash RA, Przepiorka D, Devine SM, Klein JL, Weisdorf D, et al. Phase III study comparing methotrexate and tacrolimus (prograf, FK506) with methotrexate and cyclosporine for graft-versus-host disease prophylaxis after HLA-identical sibling bone marrow transplantation. Blood. 1998;92:2303–2314. - PubMed
    1. Nash RA, Antin JH, Karanes C, Fay JW, Avalos BR, Yeager AM, et al. Phase 3 study comparing methotrexate and tacrolimus with methotrexate and cyclosporine for prophylaxis of acute graft-versus-host disease after marrow transplantation from unrelated donors. Blood. 2000;96:2062–2068. - PubMed
    1. Storb R, Deeg HJ, Pepe M, Appelbaum F, Anasetti C, Beatty P, et al. Methotrexate and cyclosporine versus cyclosporine alone for prophylaxis of graft-versus-host disease in patients given HLA-identical marrow grafts for leukemia: long-term follow-up of a controlled trial. Blood. 1989;73:1729–1734. - PubMed

Publication types