Mycophenolate-based graft versus host disease prophylaxis is not inferior to methotrexate in myeloablative-related donor stem cell transplantation

Am J Hematol. 2015 May;90(5):392-9. doi: 10.1002/ajh.23955. Epub 2015 Apr 8.

Abstract

We retrospectively reviewed 242 patients who received related donor myeloablative peripheral blood hematopoietic cell transplantation. We compared patients who received mycophenolate (MMF)/cyclosporine (CSA) (n = 71), to historical controls who received methotrexate (MTX)/CSA (n = 172). There were no differences in overall survival, nonrelapse mortality, and relapse. The MMF/CSA group had significantly faster neutrophil and platelet engraftment: medians of 13 versus 18 days and 10 versus 14 days, respectively (P = 0.001). The cumulative incidence of acute graft versus host disease (GVHD) (Grades, 2-4) was significantly lower in the MMF/CSA group (45.1 vs. 74.4%, P < 0.001). The MMF/CSA group showed a lower incidence of skin (51.5 vs. 72.1%, P < 0.001) and liver acute GVHD (11.3 vs. 54.2%, P < 0.001) and a higher incidence of lung (42.2 vs. 19.0%, P = 0.045), eye (59.7 vs. 30.1%, P < 0.001), and mouth (72.8 vs. 56.4%, P = 0.001) chronic GVHD but only eye chronic GVHD was confirmed in propensity score matching (PSM) analysis. The incidence of cytomegalovirus (CMV) viremia was higher in the MMF/CSA group (55.8 vs. 39.6%, P < 0.001) but this was not confirmed in PSM analysis. MMF/CSA was identified as an independent favorable factor for acute GVHD (P < 0.001, hazard ratio, 0.41) but as a possible adverse risk factor for CMV viremia as this was not found to be statistically significant in PSM analysis. MMF/CSA in myeloablative matched related donor peripheral blood stem cell transplant is not inferior as GVHD prophylaxis in comparison with MTX/CSA and is associated with faster engraftment but a potentially higher risk of CMV viremia.

MeSH terms

  • Adolescent
  • Adult
  • Antibiotics, Antineoplastic / therapeutic use
  • Cyclosporine / therapeutic use
  • Cytomegalovirus / immunology
  • Cytomegalovirus Infections / immunology
  • Cytomegalovirus Infections / mortality
  • Cytomegalovirus Infections / pathology
  • Cytomegalovirus Infections / therapy*
  • Female
  • Graft vs Host Disease / immunology
  • Graft vs Host Disease / pathology
  • Graft vs Host Disease / prevention & control
  • Graft vs Host Disease / therapy*
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Leukemia, Myeloid, Acute / immunology
  • Leukemia, Myeloid, Acute / mortality
  • Leukemia, Myeloid, Acute / pathology
  • Leukemia, Myeloid, Acute / therapy*
  • Male
  • Methotrexate / therapeutic use
  • Middle Aged
  • Mycophenolic Acid / therapeutic use*
  • Myeloablative Agonists / therapeutic use
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / immunology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / mortality
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy*
  • Recurrence
  • Retrospective Studies
  • Survival Analysis
  • Tissue Donors
  • Transplantation Conditioning*
  • Transplantation, Homologous

Substances

  • Antibiotics, Antineoplastic
  • Immunosuppressive Agents
  • Myeloablative Agonists
  • Cyclosporine
  • Mycophenolic Acid
  • Methotrexate