Day +60 WT1 assessment on CD34 selected bone marrow better predicts relapse and mortality after allogeneic stem cell transplantation in acute myeloid leukemia patients

Abstract

The aim of this study was to evaluate the role of WT1 expression after allogeneic stem cell transplantation (alloHSCT) in patients with acute myeloid leukemia (AML). We studied WT1 expression in bone marrow cells from 50 patients in complete remission on day +60 after transplant. WT1 was assessed on unfractionated bone marrow mononuclear cells (MNC) and on CD34+ selected cells (CD34+). A ROC curve analysis identified 800 WT1 copies on CD34+ selected cells, as the best cut-off predicting relapse (AUC 0.842, p=0.0006, 85.7% sensitivity and 81.6% specificity) and 100 copies in MNC (AUC 0.819, p=0.007, 83.3% sensitivity and 88.2% specificity). Using the 800 WT1 copy cut off in CD34+ cells, the 2 year cumulative incidence of relapse was 12% vs 38% (p=0.005), and 2 year survival 88% vs 55% (p=0.02). Using the 100 WT1 copy cut off in unfractionated MNC, the 2 year cumulative incidence of relapse 13% vs 44% (p=0.01) and the 2 year survival 88% vs 55% (p=0.08). In a multivariate Cox analysis WT1 expression in CD34 cells proved to highly predictive of relapse (p=0.004); also WT1 expression on unfractionated cells predicted relapse (p=0.03). In conclusion, day-60 WT1 expression after allogeneic HSCT is a significant predictor of relapse, particularly when tested on CD34+ selected bone marrow cells.

Bone marrow CD34+ molecular chimerism as an early predictor of relapse after allogeneic stem cell transplantation in patients with acute myeloid leukemia

“…Overall, our data are in line with other published papers, highlighting the role of both lineage specific molecular chimerism and WT1 as markers of MRD after allo-SCT ( 14 – 19 , 24 – 28 ). The issue of the superiority of molecular chimerism on CD34+ cells over other methods for leukemia relapse prediction is still unsolved.…”

“…Thus, it may be considered as a surrogate marker of MRD, which can be associated with a high probability of disease recurrence ( 14 – 17 ). Several studies have confirmed that lineage-specific molecular chimerism is a reliable marker of MRD and relapse risk ( 14 – 17 ), but the interplay between CD34+ chimerism and other markers of MRD (e.g., leukemic blasts detection with MFC or WT1 ) possibly associated with MRD persistence is poorly understood and under-studied ( 18 , 19 ).…”