Wilms Tumor Gene 1 Expression as a Predictive Marker for Relapse and Survival after Hematopoietic Stem Cell Transplantation for Myelodysplastic Syndromes

• Published in: Biology of blood and marrow transplantation 2015-03, Vol.21 (3), p.460-467
• Main Authors: Yoon, Jae-Ho, Jeon, Young-Woo, Yahng, Seung-ah, Shin, Seung-Hwan, Lee, Sung-Eun, Cho, Byung-Sik, Lee, Dong-Gun, Eom, Ki-Seong, Kim, Hee-Je, Lee, Seok, Min, Chang-Ki, Cho, Seok-Goo, Kim, Yonggoo, Kim, Dong-Wook, Lee, Jong-Wook, Han, Kyungja, Min, Woo-Sung, Park, Chong-Won, Kim, Myungshin, Kim, Yoo-Jin
• Format: Article
• Language: English
• Subjects: Adult; Aged; Allografts; Biomarkers - blood; Disease-Free Survival; Female; Gene Expression Regulation; Hematology, Oncology and Palliative Medicine; Hematopoietic Stem Cell Transplantation; Humans; Male; Middle Aged; Minimal residual disease; Myelodysplastic syndrome; Myelodysplastic Syndromes - blood; Myelodysplastic Syndromes - mortality; Myelodysplastic Syndromes - therapy; Recurrence; Relapse; Retrospective Studies; Survival; Survival Rate; Wilms tumor gene 1 (WT1); WT1 Proteins - biosynthesis
• ISSN: 1083-8791; 1523-6536
• DOI: 10.1016/j.bbmt.2014.11.008

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/104 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.