Quantitative Assessment of WT1 Gene Transcript After Hematopoietic Stem Cell Transplantation Is a Powerful MRD Marker to Predict the Clinical Outcome in Acute Leukemia

WT1 is a panleukemic marker that is expressed in 90% of acute leukemias and has been used as MRD marker after chemotherapy or transplantation. However, the threshold of WT1 to predict relapse and outcome in acute leukemia (AL) patients post transplantation has not been well studied.

We evaluated the predictive value of quantitative Wilms’ tumor gene (WTl) assessment for relapse following hematopoietic stem cell transplantation (HSCT) in patients of AL.

The quantitative assessment of WT1 expression by real-time quantitative PCR (RQ-PCR) was measured in 63 AL patients (pts) with 326 bone marrow samples at the different time points post transplant. ROC (Receiver Operating Characteristic) curve was used to determine the WT1 threshold in order to predict clinical relapses. Furthermore, AL patients were divided into WT1 positive and negative groups according to the threshold of WT1, and the clinical outcomes of these patients post transplant were analysed retrospectively.

BM samples from 19 pts who relapsed post transplanted showed significantly higher WT1 expression levels compared to the samples from 44 pts in remission (P<0.01), with a median expression level of 1270 (range 55–47596) and 132 (range 0–2959) copies WT1/10⁴ABL, respectively. Ten of 18 relapsed patients died from recurrence, and had higher levels of WT1 expression than that of other 8 patients. Based on the ROC curve, the cut-off value of WT1 was 585 copies WT1/10⁴ABL, dividing 63 patients into WT1-positive group (>585,n=21) and the negative group (≤585,n=42). The WT1-negative group had longer relapse- free survival (RFS) (P<0.01) and overall survival (OS) (P<0.01) than that of positive group.

Our data suggest that, in the HSCT setting, the sequential and quantitative analysis of WT1 may be useful as a leukemia marker for monitoring MRD, and predicting AL relapse post transplant.

No relevant conflicts of interest to declare.