The effects of immunosuppressive regimens on the outcomes of patients with hematological malignancies undergoing allogeneic stem cell transplantation remain uncertain. We conducted an individual patient data meta-analysis using data from nine randomized trials comparing allogeneic peripheral blood stem cell (PBSCT) transplants to bone marrow (BMT) transplants, focusing on the administration of three vs four doses of methotrexate (MTX) as part of a regimen for graft-versus-host-disease (GVHD) prophylaxis which included cyclosporine. Six trials containing 573 patients prescribed four doses of MTX while three trials containing 534 patients prescribed three doses of MTX. Four doses of MTX conferred a statistically significant survival advantage, resulting in death odds ratio (OR) 0.67 (CI 0.52-0.88) (P=0.0036) for recipients of PBSC compared to BM; with three doses, there was no statistically significant difference. In the four-dose studies relapse rates were 36.6% among recipients of BM compared to 19.2% among recipients of PBSC (P=0.0015). The rates of relapse in the three dose studies were 26% for both PBSC and BM. We hypothesize that the fourth dose of MTX provides extra immunosuppression among BM recipients resulting in a reduced anti-leukemic effect. This hypothesis can only be proved or disproved by a prospective, randomized trial.

Original publication

DOI

10.1038/sj.bmt.1705488

Type

Journal article

Journal

Bone Marrow Transplant

Publication Date

10/2006

Volume

38

Pages

539 - 546

Keywords

Bone Marrow Transplantation, Disease Management, Dose-Response Relationship, Drug, Graft vs Host Disease, Hematologic Neoplasms, Humans, Immunosuppressive Agents, Methotrexate, Odds Ratio, Peripheral Blood Stem Cell Transplantation, Randomized Controlled Trials as Topic, Recurrence, Survival Analysis, Time Factors, Transplantation, Homologous