medwireNews: Low-dose rabbit anti-T-lymphocyte globulin (ATLG) may improve survival over high-dose treatment in children with hematologic malignancies undergoing hematopoietic stem-cell transplantation (HSCT) from an unrelated donor, research suggests.
The randomized, open-label, phase III trial, involving 172 children from seven Italian centers, showed that patients receiving 15 mg/kg rabbit ATLG (n=88) had better overall survival and event-free survival than those receiving 30 mg/kg (n=84), without an increased risk for acute graft-versus-host disease (GVHD), relapse, or increased time to engraftment.
“ATLG at 15 mg/kg should thus be regarded as the standard serotherapy regimen for unrelated donor allogeneic HSCT in this patient population,” Franco Locatelli (Ospedale Pediatrico Bambino Gesù, Rome, Italy) and study co-authors remark.
They found that neutrophil engraftment occurred at a median of 20 days overall, with no significant difference between the two treatment groups. There was also no difference in the median time to platelet engraftment, occurring at 22 days in the 15 mg/kg ATLG group and 26 days in the 30 mg/kg ATLG group.
And there were no significant differences between the groups in the 100-day cumulative incidence of grade II–IV acute GVHD, at 36% and 29%, in the low and high dose groups, respectively, or in the cumulative incidence of disease recurrence during the median 3.4-year follow-up period, at 14% and 20%, respectively.
By contrast, the risk for non-relapse mortality was a significant 2.1-fold higher among patients who received 30 mg/kg vs 15 mg/kg ATLG, at 19% versus 9%, which the researchers note may have been driven by an increased risk for infection-related deaths. These occurred in seven high-dose patients versus three of the low-dose patients.
Moreover, the children given 30 mg/kg ATLG had significantly higher rates of Epstein-Barr virus (37 vs 23%) and adenovirus (12 vs 1%) reactivation than those given 15 mg/kg.
In addition to a higher risk for non-relapse mortality, patients in the 30 mg/kg ATLG group had a significantly lower 5-year overall survival probability, at 62%, compared with 78% for the patients in the 15 mg/kg ATLG group, as well as a significantly lower 5-year event-free survival, at 61% versus 77%.
Writing in The Lancet Oncology, Locatelli et al conclude that “15 mg/kg ATLG can spare life-threatening viral infections without significantly increasing the incidence of acute and chronic GVHD, and without adversely affecting other outcomes such as engraftment or relapse.”
They add: “Future randomised studies will continue to aim to optimise patient outcome and strategies to prevent acute GVHD occurrence.”
By Laura Cowen
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