Prognostic Factors for Post-Transplant Outcomes in Patients with Myelodysplastic Syndromes (MDS)

Abstract 2015

Allogeneic hematopoietic stem cell transplantation (AlloSCT) remains the only curative option for MDS. Several retrospective studies evaluated the impact of various prognostic factors (i.e. cytogenetic risk group, WHO classification, ferritin level etc.) on post-transplant outcomes of pts with MDS, however comprehensive analyses including a cytogenetic abnormalities detected by SNP array (SNP-A) karyotyping method have not been performed. We have analyzed prognostic factors of post-AlloSCT outcomes among 74 pts with MDS (2000–2010) including the predictive value of SNP-A abnormalities. Cox proportional hazards analysis was used to identify univariable prognostic factors for acute GVHD (aGVHD), chronic GVHD (cGVHD), disease relapse, relapse free (RFS) and overall survival (OS). Multivariable prognostic factors were identified by stepwise Cox proportional hazards analysis. The median time from MDS diagnosis to transplant for all pts was 6 mos (range, 0.2– 141 mos). The median age at transplant was 51 yrs; 32% of the pts had a hematopoietic cell transplant co-morbidity index (HCT-CI) score ≥ 3; 69% had ≥1 prior chemotherapies; and only 30% were in remission prior to their transplant. 27 pts (37%) had RAEB-2, 11 (15%) had RAEB-1, and 9 (12%) had treatment-related MDS. 42 pts (58%) belonged to an intermediate-2 or higher IPSS risk category. 23 pts (31%) had adverse karyotype (complex or monosomy 7) detected by metaphase cytogenetics (MC). SNP abnormalities were identified in 58% of patients; 79% of all patients with SNP abnormalities had lesions not previously detected by traditional cytogenetic techniques. Median pre-transplant ferritin level was 1127 (range, 9–5201). 73% of the pts received myeloablative conditioning. In 61% of cases stem cells were harvested from the bone marrow. Matched related donors accounted for half of the cases. Twelve pts (16%) died within 100 days of transplant and 39 pts (53%) within the median follow up of 36 mos (range, 5–114). MDS relapse occurred in 22 pts (30%). The rates of grade II-IV aGVHD and extensive cGVHD were 49% and 24% respectively. Disease relapse was the most common cause of death (31%) followed by aGVHD (18%) and cGVHD (13%). In univariate analysis, aGVHD was associated with myeloablative (p<0.01) and non-TBI (p=0.01) containing regimens. Disease relapse was associated with increased number of prior chemotherapy regimens (p=0.04), whereas the OS was associated with higher level of pre-transplant ferritin level (p=0.01). In multivariable analysis, only high pre-transplant ferritin level predicted for worse OS (p=0.01) and only myeloablative conditioning predicted aGVHD (p=0.01). When the group with complex cytoegenetics or ≥3 SNP abnormalities was compared with the rest of the patients, relapse occurred more frequently and RFS and OS was reduced, however the high risk group was too small to detect a statistically significant difference. Our data demonstrate elevated pre-transplant ferritin level to be the only independent predictor for inferior OS in pts with MDS undergoing AlloSCT. The prognostic role of SNP-A abnormalities in addition to chromosomal lesions detected by MC in post-transplant setting needs to be validated in a larger group of MDS pts.