Italian Study of Serotherapy to Prevent GVHD in Pediatric Hematologic Malignancy

Key Points

  • In children with hematologic malignancies, the lower dose of ATLG was associated with a nonsignificantly higher incidence of graft-vs-host disease at 100 days.
  • The lower dose of ATLG was associated with improved event-free and overall survival.

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.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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