A randomized phase II trial comparing tacrolimus and mycophenolate mofetil to tacrolimus and methotrexate for acute graft-versus-host disease prophylaxis.

Abstract

Tacrolimus (Tac) plus methotrexate (MTX) is a standard regimen for graft-versus-host disease (GVHD) prophylaxis. Mycophenolate mofetil (MMF) is sometimes used instead of MTX to minimize toxicity, despite the lack of controlled studies demonstrating efficacy. We conducted a single-center, randomized phase II trial comparing Tac + MMF to Tac + MTX. Intent-to-treat analyses included 42 patients randomized to Tac + MMF and 47 to Tac + MTX. Patient characteristics were not different between the study arms. Patients in the Tac + MMF arm were less likely to experience severe mucositis, require narcotic analgesia and parenteral nutrition, and had earlier hospital discharge. The Tac + MMF arm had the same time to neutrophil recovery, but earlier platelet recovery. The cumulative incidence of grade II-IV acute GVHD (aGVHD) at 100 days was similar (P = .8), but grade III-IV aGVHD was higher in the Tac + MMF arm (19% versus 4%; P = .03); this was predominantly seen in unrelated donor transplants (26% versus 4%; P = .04), and less in related donor transplants (11% versus 4%; P = n.s.). Moderate or severe chronic GVHD was similar (P = .71). There were no significant differences between the arms in relapse, nonrelapse mortality, or overall and relapse-free survivals. MMF was associated with less early toxicity than MTX but was not as effective in preventing severe aGVHD, especially in unrelated donor transplants.

• Authors: Janelle Perkins, Teresa Field, Jongphil Kim, Mohamed A Kharfan-Dabaja, Hugo Fernandez, Ernesto Ayala, Lia Perez, Mian Xu, Melissa Alsina, Leonel Ochoa, Daniel Sullivan, William Janssen, Claudio Anasetti
• Journal: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation (Biol Blood Marrow Transplant) Vol. 16 Issue 7 Pg. 937-47 (Jul 2010) ISSN: 1523-6536 [Electronic] United States
• PMID: 20102746 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Immunosuppressive Agents
• Mycophenolic Acid
• Tacrolimus
• Methotrexate

Topics

• Adult
• Aged
• Drug Therapy, Combination
• Female
• Graft vs Host Disease (etiology, prevention & control)
• Humans
• Immunosuppressive Agents (therapeutic use)
• Incidence
• Male
• Methotrexate (therapeutic use)
• Middle Aged
• Mycophenolic Acid (analogs & derivatives, therapeutic use)
• Prognosis
• Stem Cell Transplantation (methods)
• Tacrolimus (therapeutic use)
• Transplantation Conditioning (methods)
• Transplantation, Homologous
• Treatment Outcome
• Young Adult