graft-versus-host disease

Comparative Study of Mycophenolate Mofetil and Methotrexate in Graft-Versus-Host Disease Prophylaxis in Adult Recipients of Related and Unrelated Allo-HSCT

BONE MARROW TRANSPLANTATION , , , ,

IS Moiseev, YuA Tarakanova, AL Alyanskii, EV Babenko, MM Kanunnikov, VA Dubkova, EV Morozova, EI Darskaya, OA Slesarchuk, AD Kulagin, SN Bondarenko, BV Afanas’ev

RM Gorbacheva Scientific Research Institute of Pediatric Oncology, Hematology and Transplantation; IP Pavlov First Saint Petersburg State Medical University, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022

For correspondence: Ivan Sergeevich Moiseev, MD, PHD, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022; Tel.: +7(812)338-55-03; e-mail: moisiv@mail.ru

For citation: Moiseev IS, Tarakanova YuA, Alyanskii AL, et al. Comparative Study of Mycophenolate Mofetil and Methotrexate in Graft-Versus-Host Disease Prophylaxis in Adult Recipients of Related and Unrelated Allo-HSCT. Clinical oncohematology. 2019;12(1):43–50.

DOI: 10.21320/2500-2139-2019-12-1-43-50

ABSTRACT

Background. Although the use of methotrexate (MTX) and mycophenolate mofetil (MMF) for prophylaxis of graft-versus-host disease (GVHD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) was compared in a large number of studies, the published results are contradictory. This fact provides ground for the present retrospective single-center trial comparing these two approaches in GVHD prophylaxis.

Materials & Methods. The present study included 294 allo-HSC recipients with MTX prophylaxis and 172 allo-HSC recipients with MMF prophylaxis. 36 % of patients underwent matched related donor transplantation, and 64 % of patients received matched unrelated donor transplantation.

Results. Univariate and multivariate analyses showed that probability of acute grade 2–4 GVHD is 36 % vs. 39 % (hazard ratio [HR] 1.297; 95% confidence interval [95% CI] 0.931–1.795; p = 0.122), grade 3–4 GVHD was 21 % vs. 25 % (HR 1.472; 95% CI 0.951–2.256; p = 0.05), and probability of chronic GVHD was 52 % vs. 55 % (HR 0.978; 95% CI 0.951–1.406; p = 0.91). In the MTX and MMF groups there were no significant differences in transplantation mortality (HR 1.173; 95% CI 0.797–1.708; p = 0.43), relapse incidence (HR 1.034; 95% CI 0.743–1.428; p = 0.84), overall survival (HR 1.087; 95% CI 0.825–1.433; p = 0.55), event-free survival (HR 1.108; 95% CI 0.854–1.437; p = 0.43), disease and GVHD free survival (HR 1.065; 95% CI 0.845–1.343; p = 0.59). Engraftment occurred earlier when MMF was used (p = 0.035). Administration of MMF instead of MTX was associated with lower probability of toxic grade 3–4 hepatitis (7 % vs. 31 %; p < 0.0001) and grade 3–4 mucositis (23 % vs. 45 %; p = 0.0002).

Conclusion. The efficacy of GVHD prophylaxis using MMF is comparable with that of MTX, but MMF is associated with a better safety profile due to reduced incidence of severe liver toxicity and mucositis.

Keywords: allogeneic hematopoietic stem cell transplantation, graft-versus-host disease, prophylaxis, methotrexate, mycophenolate mofetil.

Received: May 23, 2018

Accepted: December 4, 2018

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