Prognostic impact of WT1 expression prior to hematopoietic stem cell transplantation in children with malignant hematological diseases.

PURPOSE: Malignant hematological diseases represent the most common pediatric cancer. As they cannot always be cured by chemotherapy alone, leukemia and myelodysplastic syndrome (MDS) are frequent medical indications for hematopoietic stem cell transplantation, yet even this treatment is not capable of preventing relapse for certain. Therefore, molecular markers are used to monitor minimal residual disease (MRD) to be enabled to react early to an impeding relapse. As specific markers are not always available, Wilms' tumor gene 1 (WT1) has been suggested as a universal marker, but has not yet been established clinically.
METHODS: We determined the level of WT1 gene expression in 130 children, adolescents and young adults with malignant hematological diseases prior to transplantation and evaluated its impact on patients' outcome. A real-time quantitative RT-PCR was used for this purpose.
RESULTS: The relationship between a high level of WT1 and the cumulative incidence of relapse, event-free survival and overall survival proved to be highly significant in univariate and multivariate analyses. Forty-eight percent of all patients with high WT1 levels suffered from a relapse, whereas only eight percent showing normal WT1 levels before transplantation relapsed. The most convincing result was found for acute myeloid leukemia (AML) and MDS.
CONCLUSION: We conclude that WT1 expression prior to transplantation qualifies as an independent prognostic factor and should be further evaluated for MRD monitoring. It might especially be useful for patients with AML or MDS missing specific markers.