Wilms tumor gene 1 expression as a predictive marker for relapse and survival after hematopoietic stem cell transplantation for myelodysplastic syndromes

Biol Blood Marrow Transplant. 2015 Mar;21(3):460-7. doi: 10.1016/j.bbmt.2014.11.008. Epub 2014 Nov 20.

Abstract

Relapse after allogeneic hematopoietic stem cell transplantation (HSCT) is a major concern in myelodysplastic syndromes (MDS), but the role of Wilms tumor gene 1 (WT1) as a predictive marker for post-HSCT relapse remains to be validated. We measured WT1 transcript levels by real-time quantitative PCR from marrow samples of 82 MDS patients who underwent transplantation between 2009 and 2013. Pre-HSCT WT1 expression weakly correlated with marrow blast counts or International Prognostic Scoring System scores and failed to predict post-transplantation relapse. Regarding post-HSCT WT1, transcript levels of relapsed patients were significantly higher in comparison to those in remission. Further analysis using receiver operating characteristics curves showed that higher (>154 copies/10(4)ABL) 1-month post-HSCT WT1 resulted in a higher 3-year relapse rate (47.2% versus 6.9%, P < .001) with poorer disease-free survival (DFS) and overall survival at 3 years (41.7% versus 79.0% and 54.3% versus 82.1%, P = .003 and P = .033, respectively). Multivariate analysis after adjusting for pre-HSCT karyotype and chronic graft-versus-host disease (GVHD) also revealed that higher 1-month post-HSCT WT1 was an independent predictive marker for subsequent relapse (P = .002) and poorer DFS (P = .010). In the higher 1-month post-HSCT WT1 subgroup, patients with chronic GVHD showed lower relapse rate and favorable survival outcome. One month post-HSCT WT1 expression was a useful marker for minimal residual disease and relapse prediction in association with chronic GVHD in the context of HSCT for MDS.

Keywords: Hematopoietic stem cell transplantation; Minimal residual disease; Myelodysplastic syndrome; Relapse; Survival; Wilms tumor gene 1 (WT1).

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Allografts
  • Biomarkers / blood
  • Disease-Free Survival
  • Female
  • Gene Expression Regulation*
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Male
  • Middle Aged
  • Myelodysplastic Syndromes* / blood
  • Myelodysplastic Syndromes* / mortality
  • Myelodysplastic Syndromes* / therapy
  • Recurrence
  • Retrospective Studies
  • Survival Rate
  • WT1 Proteins / biosynthesis*

Substances

  • Biomarkers
  • WT1 Proteins
  • WT1 protein, human