Sensitivity of Pediatric Myelodysplastic Syndromes With Excess of Blasts With UBTF-TD to Venetoclax/Azacitidine.

UBTF-TD has been reported in a significant percentage of childhood MDS-EB and has been associated with inferior survival compared to that of patients with the wild-type gene. We treated three consecutive pediatric patients affected by UBTF-TD MDS-EB with venetoclax and azacitidine (ven/aza) in combination as 28-day cycles on a compassionate use basis three consecutive pediatric patients affected by UBTF-TD MDS-EB as a bridge to allogeneic HSCT. Treatment with ven/aza was well-tolerated, and all patients responded to the ven/aza course, achieving CR with flow-cytometry negativity. All three patients were bridged to myeloablative HSCT. All patients are disease-free and graft-versus-host disease-free at last follow-up. Comprehensive biological characterization of the disease showed (i) high expression of the BCL2 gene, paralleled by a low expression of BCL2A1 and MCL1; (ii) overexpression of both HOXA and HOXB; and (iii) a distinct methylation signature of patients with UBTF-TD myeloid neoplasms.