Background
Biologic-assignment trial (donor vs no-donor, by a 90-day donor search) enrolling 384 patients aged 50-75 with de novo intermediate-2 or high-risk MDS by IPSS who were candidates for reduced-intensity conditioning (RIC) allo-HCT from an HLA-matched related or 8/8 matched unrelated donor. Median age 65.7 years; 69% high/very-high IPSS-R.
Interventions and follow up
Arm A (donor): RIC allogeneic HCT within 6mo of enrollment for patients with HLA-matched related or 8/8 matched unrelated donor
Arm B (no donor): Hypomethylating agent therapy or supportive care
Primary endpoint: 3-year overall survival
mFollow up: ~3 years
Arm B (no donor): Hypomethylating agent therapy or supportive care
Primary endpoint: 3-year overall survival
mFollow up: ~3 years
Results
3-yr OS: 47.9% vs 26.6%, arm A vs B; P=.0001
3-yr LFS: 35.8% vs 20.6%, arm A vs B; P=.003
QOL: no significant differences between arms
100-day / 1-yr TRM (donor arm): 7.4% and 15.5%
IPSS risk (MVA): higher score predicted worse OS (HR 1.85, 95%CI 1.21–2.83; P=.004) and LFS (HR 2.17, 95%CI 1.47–3.20; P<.0001)
No-donor patients later transplanted (n=25): 3-yr OS and LFS both 58.5%
3-yr LFS: 35.8% vs 20.6%, arm A vs B; P=.003
QOL: no significant differences between arms
100-day / 1-yr TRM (donor arm): 7.4% and 15.5%
IPSS risk (MVA): higher score predicted worse OS (HR 1.85, 95%CI 1.21–2.83; P=.004) and LFS (HR 2.17, 95%CI 1.47–3.20; P<.0001)
No-donor patients later transplanted (n=25): 3-yr OS and LFS both 58.5%
Adverse events
GVHD: Grade II-IV acute GVHD 43.1% and grade III-IV 17.1% by day 100; chronic GVHD 55.5% by 27mo (40 moderate, 23 severe)
Transplant-related mortality/infections: Non-relapse mortality higher in the HCT arm (100-day 7.4%, 1-yr 15.5%) with typical post-transplant infections, offset by reduced disease relapse
Transplant-related mortality/infections: Non-relapse mortality higher in the HCT arm (100-day 7.4%, 1-yr 15.5%) with typical post-transplant infections, offset by reduced disease relapse
Conclusions
In patients aged 50-75 with intermediate-2/high-risk MDS who are RIC-eligible and have a matched donor, RIC allo-HCT significantly improved 3-year OS and LFS versus no-donor management with HMA or supportive care.
Key Limitations
Biologic-assignment (donor vs no-donor) rather than randomized design; modest numbers of late transplants in the no-donor arm; HMA-based comparator predates newer MDS therapies; excluded patients planned for myeloablative or alternative-donor transplant, limiting generalizability.
Clinical Context
Provides high-level evidence that RIC allo-HCT improves survival in older patients with advanced MDS and supports donor searches in this group. ASCO/ELN and transplant-society guidance endorse allo-HCT for fit patients aged 50-75 with higher-risk MDS and a suitable matched donor.