Peripheral Blood WT1 Expression Predicts Relapse in AML Patients Undergoing Allogeneic Stem Cell Transplantation

Abstract

To evaluate if WT1 expression may predict relapse after allo-SCT, we analyzed WT1 levels on peripheral blood (PB) and bone marrow (BM) before and after allo-SCT in 24 AML patients with WT1 overexpression at diagnosis. Five copies of WT1/ABL × 104 from PB were identified as the threshold value that correlated with relapse after allo-SCT. The same correlation was not identified when WT1 expression was assessed from bone marrow (BM). Eight out of 11 (73%) patients with a pre-allo-SCT PB-WT1 ≥ 5 and 4/13 (31%) patients with a pre-allo-SCT PB-WT1 < 5 relapsed, respectively (P = 0.04). The incidence of relapse was higher in patients with PB-WT1 ≥ 5 measured after allo-SCT, at the 3rd (56% versus 38%; P = 0.43) and at the 6th month (71% versus 20%; P = 0.03). Patients with pretransplant PB-WT1 < 5 had significantly better 2-year OS and LFS than patients with a PB-WT1 ≥ 5 (81% versus 0% and 63% versus 20%) (P = 0.02). Our data suggest the usefulness of WT1 monitoring from PB to predict the relapse in allotransplanted AML patients and to modulate the intensity of conditioning and/or the posttransplant immunosuppression in an attempt to reduce the posttransplant relapse risk.

WT1 Expression in Circulating RNA as a Minimal Residual Disease Marker for AML Patients After Stem-Cell Transplantation

“…Therefore, a rising trend of WT1 expression indicates forthcoming clinical relapse. This is consistent with findings reported by Malagola et al [32]. We propose that patients who show changes in WT1 expression should be monitored more carefully and, if possible, treatment of the impending relapse should be started pre-emptively.…”

“…Polák et al [20] noted that on the basis of BM-RNA the upper remission level was estimated to be the relative (WT1/ABL) expression of WT1 = 0.02. Malagola et al [32] chose five copies of WT1/ABL 9 10 4 from PB-RNA as the threshold value that correlated with relapse after allogeneic stem-cell transplantation [32]. In this study, we found that the WT1 expression level increased significantly, both in BM-RNA and CRNA, before clinical relapse.…”

Postremission sequential monitoring of minimal residual disease by WT1 Q‐PCR and multiparametric flow cytometry assessment predicts relapse and may help to address risk‐adapted therapy in acute myeloid leukemia patients

“…Only taking into account the dynamic nature of this phenomenon, we can explain the discordance of the cut‐off values for positive versus negative samples observed by different groups. Also in our experience, for example, the predictive value of PB‐WT1 ≥ 16 × 10 4 ABL copies measured after 1st intensification is greater than PB‐WT1 ≥ 5 × 10 4 ABL copies measured before transplantation after completion of the treatment program, as already published on a selected cohort of the same patients .…”

“…Bone marrow and PB quantitative assessment of WT1 molecular levels was performed by Q‐PCR according to the ELN method as previously published .…”

Optimizing peripheral blood stem cells transplantation outcome through amend relapse and graft failure: a review of current literature

“…In this strategy, Wilms tumor-1 (WT1) gene expression exceeding 100 copies/10 4 abelson murine leukemia-1 (ABL1) in bone marrow (BM) or WT-1 ≥5 copies/10 4 ABL1 in peripheral blood, with BM in remission status (<5% blasts simultaneously with morphology and cytometry symptoms) is surrogate for starting DLI [ 45 , 48 ]. In absence of GVHD for HLA identical siblings transplantation, the starting dosage is 1 × 10 6 /kg CD3+ cells and subsequently, half log increments every 30–60 days until MRD becomes negative.…”