Background
Open-label phase 3, N=407, age 14–70 with AML or MDS-EB1/2 undergoing haploidentical peripheral blood stem cell transplant; randomized 2:1:1 across three GVHD prophylaxis strategies. First randomized comparison of the ATG-based (Beijing) and PTCy-based (Baltimore) platforms plus a low-dose combination.
Results
Interventions and follow up: Arm A: low-dose ATG (5 mg/kg) + low-dose PTCy (50 mg/kg) (n=185)
Arm B: standard-dose ATG (10 mg/kg total) (n=113)
Arm C: PTCy-based (100 mg/kg total) (n=109)
Primary endpoint: coprimary — grade 2–4 aGVHD by day +100; 1-yr GRFS
mFollow up: NR (2-yr outcomes reported)
Results: Grade 2–4 aGVHD by day +100: no significant difference across arms (P=.210)
1-yr GRFS: comparable across arms (NR)
2-yr moderate-severe cGVHD: 17.4% (ATG/PTCy) vs 17.3% (ATG) vs 28.3% (PTCy), P=.095
Survival (OS/DFS): no significant differences
Neutrophil/platelet recovery: significantly faster with ATG/PTCy (P<.001)
Arm B: standard-dose ATG (10 mg/kg total) (n=113)
Arm C: PTCy-based (100 mg/kg total) (n=109)
Primary endpoint: coprimary — grade 2–4 aGVHD by day +100; 1-yr GRFS
mFollow up: NR (2-yr outcomes reported)
Results: Grade 2–4 aGVHD by day +100: no significant difference across arms (P=.210)
1-yr GRFS: comparable across arms (NR)
2-yr moderate-severe cGVHD: 17.4% (ATG/PTCy) vs 17.3% (ATG) vs 28.3% (PTCy), P=.095
Survival (OS/DFS): no significant differences
Neutrophil/platelet recovery: significantly faster with ATG/PTCy (P<.001)
Adverse events
Engraftment: cumulative incidence of neutrophil and platelet recovery highest with low-dose ATG/PTCy
Infections/toxicity rates: NR in abstract
Infections/toxicity rates: NR in abstract
Conclusions
The three prophylaxis strategies yielded similar grade 2–4 aGVHD and survival after haplo-PBSCT. Low-dose ATG/PTCy delivered faster hematologic recovery with numerically less moderate-severe cGVHD than full-dose PTCy, supporting it as a practical alternative platform.
Key Limitations
Open-label; conducted entirely in China (AML/MDS, younger median age) — generalizability to Western practice uncertain. No arm was superior on the coprimary endpoints; cGVHD difference not significant (P=.095) and underpowered for three-way comparisons. PBSC grafts only.
Clinical Context
PTCy (Baltimore protocol) is the de facto global standard for haplo-HCT; ATG-based prophylaxis (Beijing protocol) dominates in China. This first randomized head-to-head suggests equipoise on GVHD/survival, with engraftment kinetics favoring the low-dose combination; accompanying Blood commentary frames it as platform-convergence data.