Outcomes associated with a steroid-containing acute GVHD prophylaxis regimen for matched unrelated donor (MUD) hematopoietic stem cell transplantation

Abstract

Background: Previously reported randomized trials have yielded differing conclusions about the addition of steroids to GVHD prophylaxis for patients undergoing sibling allogeneic transplant. Prophylaxis with cyclosporine plus methotrexate after MUD transplant has a reported grade 2–4 acute GVHD incidence of 74%. MUD transplantation was initiated at OHSU in 1996 using a 3-drug combination of cyclosporine, methotrexate, and steroids in a single-arm prospective protocol to examine the incidence and severity of GVHD and survival. Methods: The analysis included all patients undergoing MUD transplant who received GVHD prophylaxis with cyclosporine 2 mg/kg iv BID from day −2, methotrexate 15 mg/m2 iv on day +1 and 10 mg/m2 iv on days +3 and +6, and methylprednisolone 0.25 mg/kg iv BID beginning on day +7 and tapering at day +28. Patients were stratified by disease risk per CIBMTR classification. Patients with relapse and no GVHD were censored for GVHD outcomes at therapeutic withdrawal of immunosuppression. Results: 124 patients received the 3-drug regimen, including 50 with low-risk, 43 with intermediate-risk, and 31 with high-risk disease. One hundred sixteen (94%) of the MUD grafts were matched at 6 out of 6 HLA-antigens. Eight patients were not evaluable for GVHD due to death prior to engraftment. The maximum grade of acute GVHD is shown in Table 1. Sixty-four (55%) had grade 0–1 acute GVHD. Fifty-two (45%) developed grade 2–4 acute GVHD at a median onset of day +29. Twenty-eight (24%) developed grade 3–4 acute GVHD. Patients with low-risk disease had a median survival of 29 months and a 5-year OS of 42%, whereas those with intermediate/high-risk had a median survival of 10 months and a 5-year OS of 23%. The rate of disease relapse was 15% for both the low and intermediate/high-risk groups. Preliminary infection analysis among 64 patients demonstrated an incidence of all infections greater than 70%. Conclusions: The observed rate of grade 3–4 acute GVHD using a 3-drug prophylaxis strategy that includes steroids after MUD transplantation was low and delayed in onset when compared to previous trials of 2-drug combinations. The rate of disease relapse was low and the overall survival was comparable to other published strategies. Preliminary analysis suggests a high rate of infections. Additional analyses are planned to explore rates of chronic GVHD, as well as other potential steroid-related events such as hyperglycemia, musculoskeletal complications, alveolar hemorrhage or thrombotic microangiopathy (Table). Tabled 1Maximum Acute GVHD GradeNumberPercentGrade 04034%Grade 12421%Grade 22421%Grade 31513%Grade 41311% Open table in a new tab