Allogeneic stem cell transplantation-related outcomes in myelodysplastic syndromes.

Abstract

6567 Background: Allogeneic stem cell transplantation (SCT) is the only known curative modality in myelodysplastic syndromes (MDS). Its use has historically been limited due to older patient age and comorbidity burden. Recent advances in reduced-intensity conditioning (RIC) have expanded the use of SCT in MDS. Methods: This was a retrospective single center database review study to evaluate contemporary outcomes in SCT-treated MDS. We identified all patients with newly diagnosed MDS presenting to our center between Jan 2000 and Mar 2023 and stratified them by receipt of SCT. Biallelic TP53 -mutated status was defined as 2 TP53 mutations, VAF ≥ 50%, or concomitant del(17p). Landmark analyses were performed to compare outcomes with or without SCT (median time from diagnosis to SCT as landmark). Results: 3649 patients with newly-diagnosed MDS were included. 573 (16%) underwent SCT. 4-week, 8-week, and 100-day mortality were 3%, 6%, and 14%, respectively. Acute GVHD occurred in 64% of patients (14% grade 3/4). Chronic GVHD occurred in 33%. Patients undergoing SCT (ages 18-77) had a median OS of 25 m from SCT day 0. The 5-year cumulative incidences of death and relapse were 21% and 31% with myeloablative conditioning (MAC) and 27% and 36% with reduced-intensity conditioning (RIC). Stratified by IPSS-R, the median OS post-SCT was 136, 40, 92, 103, and 8 m in Very Low, Low, Intermediate, High, and Very High risk. Patients with TP53 wt, TP53 mut monoallelic, and TP53 mut biallelic had a median OS of not reached (NR), 9 m, and 7 m. Patients with non-complex, complex (3 abn), and very complex (> 3 abn) CG had a median OS of 96 m, 14 m, and 7 m. Transplanted patients without TP53 mutations had 5-year OS of 59% and those without complex CG had 5-year OS of 54%. Immediate pre-SCT blasts <5% and 5-9% were associated with similar post SCT OS (median 29 and 30 m) whereas patients with 10-19% (8 m) and > 20% (12 m) had inferior survival. Multivariate analysis identified bone marrow ring sideroblast %, TP53 mutations, haplo donor, pre-SCT transformation to AML, and increasing donor age as associated with worse post-SCT OS while receipt of venetoclax pre-SCT and higher Karnofsky score were favorable. By landmark analyses, SCT was associated with improved OS across IPSS-R risk categories. Median OS was 185 m with SCT vs 82 m without SCT in Very Low risk (p<0.01), 107 vs 58 m in Low risk (p<0.01), 103 vs 31 m in Intermediate risk (p<0.01), 108 vs 18 m in High risk (p<0.01), and 16 vs 13 m in Very High risk (p<0.01). No significant benefit of SCT was noted in patients with TP53 mutations. The median OS was 27 m with SCT vs 17 m without SCT in TP53 mut monoallelic (p=0.10) and 14 vs 13 m in TP53 mut biallelic (p=0.16). Conclusions: SCT is curative in 50-60% of patients with MDS without TP53 mutations or complex CG. Efforts should be made to improve accessibility of SCT in this population. Alternative therapies are urgently needed in patients with TP53 mutations or complex CG.