Prognostic significance of WT-1 levels in patients with myelodysplastic syndrome and leukemia after reduced-intensity allogeneic transplantation
6524 Background: Expression of WT-1, a zinc-finger transcription factor, is elevated at diagnosis in many kinds of leukemia. The prognostic significance of the WT-1 transcript level before and after stem cell transplant is controversial. We performed real-time quantitative PCR (RQ-PCR) on samples from pts with leukemia and MDS undergoing allo stem-cell transplant (SCT) to determine if WT-1 expression correlates with survival (OS) and/or disease-free survival (DFS). Methods: Pts were conditioned with fludarabine, melphalan and alemtuzumab. cDNA was synthesized for RQ-PCR, which was performed on bone marrow (BM) and peripheral blood (PB) samples drawn prior to transplant admission and at day 28 (D28) post transplantation. All samples were analyzed using LightCycler technology and reported as a normalized ratio of WT-1 copy number to ABL copy number. Results: Data on 48 patients who underwent allo SCT are reported here. During a median follow up of 17 months, 24 patients died and the OS rate at one year was 52%. The DFS rate at one year was 34%. There was a statistically significant association between pretransplant WT-1 levels measured in PB and OS, with increase in risk of death by 36% for every 10 fold increase in WT-1 levels (p=0.048). Pretransplant WT-1 levels in both PB and BM also predicted DFS: the risk of relapse or death was increased by 44% (PB) and 71% (BM) for every 10 fold increase in WT-1 levels (p=0.012; p=0.048). However, after controlling for disease status at transplantation using a Cox model, pretransplant WT-1 levels were no longer a significant predictor because these levels were highly correlated with disease status at transplantation. We did not find any significant correlation between WT-1 levels 28 days post-transplantation and outcome. Conclusions: Our preliminary results differ from several published studies demonstrating prognostic significance of WT-1 RQ-PCR after allo SCT. Although elevated WT-1 levels prior to transplantation correlate with higher risk of post-transplant relapse and death from any cause, these preliminary data fail to establish an independent prognostic role for WT-1 RQ-PCR in the setting of reduced intensity allo SCT. Analysis of additional post-transplant time points is proceeding. No significant financial relationships to disclose.