New evidence published in The Lancet Oncology shows that pediatric patients with hematological malignancies who receive allogeneic hemopoietic stem-cell transplantation (HSCT) from an unrelated donor have greater benefit from a 15 mg/kg vs a 30 mg/kg dose of rabbit anti-T-lymphocyte globulin (ATLG).1
ATLG is commonly used as preventative therapy for acute and chronic graft-versus-host disease (GVHD), a severe complication in patients who receive allogeneic HSCT. Prior studies demonstrated that ATLG can prevent acute and chronic GVHD, though the optimal dose was not previously determined.
This open-label phase 3 trial (ClinicalTrials.gov Identifier: NCT00934557) randomly assigned 172 pediatric patients who underwent HSCT 1:1 to receive intravenous 15 mg/kg or 30 mg/kg ATLG over 3 days.
The 15 mg/kg ATLG arm had a 100-day cumulative incidence of grade 2 to 4 acute GVHD of 36% (95% CI, 28-48) vs 29% (95% CI, 20-40) in the 30 mg/kg arm (hazard ratio [HR], 0.74; 95% CI, 0.44-1.25; P = .26).
Non-relapse mortality in the 15 mg/kg group was 9% (95% CI, 5-18) vs 19% (95% CI, 12-30) in the 30 mg/kg group (HR, 2.08, 95% CI, 0.89-4.96; P = .092).
Five-year overall survival probability in the 15 mg/kg group was 78% (95% CI, 69-87) vs 62% (95% CI, 50-73) in the 30 mg/kg group (HR, 1.80; 95% CI, 1.01-3.20; P = .045).
Five-year event-free survival in the 15 mg/kg group was 77% vs 61% in the 30 mg/kg group (HR 1.87; 95% CI, 1.07-3.28; P = .028).
The study demonstrates that 15 mg/kg ATLG not only significantly improved survival probability, but also did not affect time to engraftment or increase the rate of acute and chronic GVHD vs 30 mg/kg.
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The authors concluded that ATLG 15 mg/kg should be considered “the standard serotherapy regimen for unrelated donor allogeneic HSCT in this patient population.”
- Locatelli F, Bernardo ME, Bertaina A, et al. Efficacy of two different doses of rabbit anti-T-lymphocyte globulin to prevent graft-versus-host disease in children with haemotological malignancies transplanted from an unrelated donor: a multicenre, randomized, open-label, phase 3 trial. Lancet Oncol. 2017 Jul 10. doi: 10.1016/S1470-2045(17)30417-5 [Epub ahead of print]