Italian Study of Serotherapy to Prevent GVHD in Pediatric Hematologic Malignancy
In an Italian phase III trial reported by Locatelli et al in The Lancet Oncology, a lower vs higher dose of rabbit anti–T-lymphocyte globulin (ATLG) was associated with a nonsignificantly greater incidence of acute graft-vs-host disease but better event-free and overall survival in children with hematologic malignancies undergoing allogeneic hematopoietic stem cell transplantation from an unrelated donor.
Study Details
In the open-label trial, 172 evaluable patients (aged 0 to 18 years) from 7 Italian centers were randomized between January 2008 and September 2011 to receive ATLG at 30 mg/kg (n = 84) or 15 mg/kg (n = 88) given intravenously over 3 days (day –4 to –2). All patients received myeloablative treatment and cyclosporine plus short-term methotrexate as post-transplantation graft-vs-host disease prophylaxis. Randomization was stratified by degree of human leukocyte antigen (HLA) compatibility, source of hematopoietic stem cells, and disease risk category. The primary endpoint was 100-day cumulative incidence of grade II to IV acute graft-vs-host disease.
Graft-vs-Host Disease and Survival Outcomes
Median follow-up was 3.4 years. The 100-day cumulative incidence of grade II to IV acute graft-vs-host disease was 36% in the 15-mg/kg group vs 29% in the 30-mg/kg group (hazard ratio [HR] = 0.74, P = .26). The cumulative incidence of nonrelapse mortality was 9% vs 19% (HR = 2.08, P = .092). Cumulative incidence of disease recurrence was 14% vs 20% (HR = 1.54, P = .25). Rates of 5-year overall survival were 78% vs 62% (HR = 1.80, P = .045). Five-year event-free survival was 77% vs 61% (HR = 1.87, P = .028).
The investigators concluded: “Children with haematological malignancies transplanted from unrelated donors selected through high-resolution HLA typing benefit from the use of a 15 mg/kg ATLG dose in comparison with a 30 mg/kg ATLG dose. ATLG at 15 mg/kg should thus be regarded as the standard serotherapy regimen for unrelated donor allogeneic [hematopoietic stem cell transplantation] in this patient population. Future randomised studies will continue to aim to optimise patient outcome and strategies to prevent acute [graft-vs-host disease] occurrence.”
The study was funded by Fresenius/Neovii Biotech.
Franco Locatelli, MD, of IRCSS, of Ospedale Pediatrico Bambino Gesù, Rome, is the corresponding author of The Lancet Oncology article.
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