GRAFT-VERSUS-HOST-DISEASE PROPHYLAXIS FOR MATCHED UNRELATED DONOR BONE-MARROW TRANSPLANTATION - COMPARISON BETWEEN CYCLOSPORINE-METHOTREXATE AND CYCLOSPORINE-METHOTREXATE-METHYLPREDNISOLONE

We performed a sequential study comparing two regimens, cyclosporine-m ethotrexate (CsA-MTX) and cyclosporine-methotrexate-methylprednisolone (CsA-MTX-MP) for graft-versus-host disease (GVHD) prophylaxis in pati ents undergoing matched unrelated donor bone marrow transplantation (M UD BMT). Study end-points were the development of GVHD, various infect ious complications and survival. Twenty nine patients with malignant h ematologic disease without HLA-compatible family donors were treated b etween May 1990 and November 1993. All donors were volunteers from the National Marrow Donor Program (NMDP) serologically HLA-A, B and DR id entical. MLC reactivity and high resolution DR DNA typing were not use d to exclude donors. Sixteen patients received CsA-MTX and 13 patients received CsA-MTX-MP. CsA and MTX doses were the same in both groups: CsA 1.5 mg/kg i.v. over 2 h every 12 h beginning the day prior to tran splant (day-1) and MTX 10 mg/m(2) i.v. bolus on days +1, +3 and +6 wit h leucovorin on days +2, +4 and +7. MP was administered at a dose of 0 .25 mg/kg i.v. every 12 h beginning on day +7 and increased to 0.5 mg/ kg on day +14. Beginning on day +35 MP and CsA were tapered 5% per wee k with targeted discontinuation at 6 months. Both groups were comparab le for primary disease, preparative regimen, recipient age (median 33 vs 33 years), donor age (median 39 vs 39.5 years), donor-recipient sex , donor ABO mismatch and serologic CMV positivity. All patients receiv ed similar supportive care. Acute GVHD grade II, III and IV developed in nine patients (56.3%, 95% CI 33-77%) in the CsA-MTX group and 10 pa tients (76.9%, 95% CI 50-92%) in the CsA-MTX-MP group (P > 0.1). Grade O and I acute GVHD developed in seven patients (43.8%, 95% CI 23-67%) in the CsA-MTX group and in three patients (23.1%, 95% CI 8-50%) in t he CsA-MTX-MP group (P > 0.1). Analyzing only patients who survived >1 00 days after transplant, 10 patients (76.9%, 95% CI 50-92%) in the Cs A-MTX group and three patients (50%, 95% CI 19-81%) in tire CsA-MTX-MP group developed chronic GVHD (P > 0.1). Infectious complications were similar in both groups. At the time of analysis, eight patients recei ving CsA-MTX and four patients receiving CsA-MTX-MP were alive. The ac tuarial survival of CsA-MTX patients was 50% at 1020 days (median surv ival 461 days) compared with 30% at 368 days (median survival 98 days) in the CsA-MTX-MP group (P = 0.07). In this study, the addition of MP to CsA-MTX provided no advantage for the prevention of severe acute o r chronic GVHD or long-term survival. Thus, CsA-MTX remains as subopti mal GVHD prophylaxis for patients undergoing matched unrelated BMT and no benefit is derived by the addition of methylprednisolone.