Cyclosporine in combination with mycophenolate mofetil versus methotrexate for graft versus host disease prevention in myeloablative HLA-identical sibling donor allogeneic hematopoietic cell transplantation.

Abstract

Graft-versus-host disease (GVHD) remains a major cause of morbidity and mortality in allogeneic hematopoietic cell transplantation (HCT) despite current prophylaxis. Methotrexate (MTX) with a calcineurin inhibitor (CNI) is the current standard, however, has several toxicities. Mycophenolate mofetil (MMF) is frequently used in reduced-intensity HCT, but data in myeloablative transplants is limited. We thus retrospectively identified 241 patients who underwent myeloablative HCT from an HLA-identical sibling donor; 174 patients received cyclosporine (CSA) + MMF and 67 received CSA+MTX. Patients receiving MMF + CSA had rapid neutrophil (median 11 vs. 19 days with MTX+CSA), and platelet recovery (median 19 vs. 25 days), lower incidence of severe mucositis by OMAS (19% vs. 53%), and shorter length of hospital stay (median 25 vs. 36 days) (P < 0.001 for all comparisons). There were no significant differences in incidence of grade 2-4 (MMF+CSA 37% vs. MTX+CSA 39%) or 3-4 acute GVHD (17% vs. 12%), chronic GVHD (46% vs. 56%), relapse (28% vs. 27%), non-relapse mortality (20% vs. 27%), or overall survival (47% vs. 44%) (P = NS for all). However, in multivariable analysis, the use of MMF+CSA was associated with an increased risk of severe grade 3-4 acute GVHD (HR 2.92, 95% CI 1.2-7.15, P = 0.019). There were no differences between the two regimens in multivariable analyses for other survival outcomes. This analysis demonstrates that the use of MMF in myeloablative sibling donor transplantation is well tolerated. However, there may be an increased risk of severe GVHD with MMF+CSA compared to MTX+CSA. Further studies evaluating optimal dosing strategies are needed.

• Authors: Betty K Hamilton, Lisa Rybicki, Robert Dean, Navneet S Majhail, Housam Haddad, Donna Abounader, Rabi Hanna, Ronald Sobecks, Hien Duong, Brian T Hill, Edward Copelan, Brian Bolwell, Matt Kalaycio
• Journal: American journal of hematology (Am J Hematol) Vol. 90 Issue 2 Pg. 144-8 (Feb 2015) ISSN: 1096-8652 [Electronic] United States
• PMID: 25353395 (Publication Type: Journal Article)
• Copyright: © 2014 Wiley Periodicals, Inc.

Chemical References

• Myeloablative Agonists
• Cyclosporine
• Mycophenolic Acid
• Methotrexate

Topics

• Acute Disease
• Adolescent
• Adult
• Aged
• Blood Platelets (immunology)
• Chronic Disease
• Cyclosporine (therapeutic use)
• Drug Therapy, Combination
• Female
• Graft vs Host Disease (immunology, mortality, pathology, therapy)
• Hematologic Neoplasms (immunology, mortality, pathology, therapy)
• Hematopoietic Stem Cell Transplantation
• Histocompatibility Testing
• Humans
• Male
• Methotrexate (therapeutic use)
• Middle Aged
• Mycophenolic Acid (analogs & derivatives, therapeutic use)
• Myeloablative Agonists (therapeutic use)
• Neutrophils (immunology)
• Recurrence
• Retrospective Studies
• Siblings
• Survival Analysis
• Tissue Donors
• Transplantation, Homologous