Background
Prospective, multicenter, open-label, randomized phase III study of 168 patients with acute leukemia, testing whether adding anti-human T-lymphocyte immune globulin (ATG) to a myeloablative conditioning regimen reduces chronic GVHD after allogeneic peripheral-blood stem-cell transplantation from an HLA-identical sibling.
Interventions and follow up
Arm A: ATG added to myeloablative conditioning regimen
Arm B: No ATG (conditioning without ATG)
Primary endpoint: Cumulative incidence of chronic GVHD at 2 years
mFollow up: 24 months
Arm B: No ATG (conditioning without ATG)
Primary endpoint: Cumulative incidence of chronic GVHD at 2 years
mFollow up: 24 months
Results
2-yr cumulative chronic GVHD: 32.2% (ATG; 95% CI 22.1–46.7) vs 68.7% (no ATG; 95% CI 58.4–80.7), P<.001
2-yr RFS: 59.4% vs 64.6%, P=.21 (similar)
2-yr OS: 74.1% vs 77.9%, P=.46 (similar)
2-yr cGVHD-free, relapse-free survival (composite): 36.6% vs 16.8%, P=.005
2-yr RFS: 59.4% vs 64.6%, P=.21 (similar)
2-yr OS: 74.1% vs 77.9%, P=.46 (similar)
2-yr cGVHD-free, relapse-free survival (composite): 36.6% vs 16.8%, P=.005
Adverse events
Between-group safety: No significant differences in relapse, infectious complications, acute GVHD, or adverse events
Net effect: Reduction in chronic GVHD with ATG was achieved without an excess of infection or relapse
Net effect: Reduction in chronic GVHD with ATG was achieved without an excess of infection or relapse
Conclusions
Adding ATG to myeloablative conditioning significantly lowered chronic GVHD (32.2% vs 68.7%) without compromising relapse-free or overall survival, and improved the composite chronic GVHD-free, relapse-free survival endpoint, supporting ATG as effective chronic GVHD prophylaxis in HLA-identical sibling transplantation.
Key Limitations
Modest sample size (N=168) limits power for survival endpoints. Restricted to HLA-identical sibling peripheral-blood grafts, so results do not directly extend to unrelated-donor, haploidentical, or bone-marrow grafts. The 2-year follow-up does not capture long-term immune reconstitution or late infection risk. Predates routine post-transplant cyclophosphamide, the dominant contemporary GVHD prophylaxis comparator.
Clinical Context
This trial provided high-quality randomized evidence that ATG reduces chronic GVHD in matched-sibling PBSC transplantation, complementing earlier unrelated-donor data (Finke Lancet Oncol 2009; Walker Lancet Oncol 2016). ATG-based prophylaxis remains widely used, particularly in Europe, though post-transplant cyclophosphamide has since emerged as a competing platform across donor types. The findings support individualized prophylaxis selection to balance chronic GVHD reduction against immune reconstitution.