Favorable outcome in TCF3::HLF-positive pediatric B-cell acute lymphoblastic leukemia without classic metabolic...

The t(17;19)(q22;p13) translocation, generating the TCF3::HLF fusion oncogene, occurs in < 1% of pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) and is associated with extreme chemotherapy resistance, frequent metabolic complications including hypercalcemia and disseminated intravascular coagulation (DIC), both of which have been reported with variable frequencies across published cohorts depending on the underlying TCF3::HLF fusion subtype, together with an extremely poor long-term prognosis. A 3-year-old girl with TCF3::HLF-positive BCP-ALL presented with fever, lethargy, and pancytopenia, but notably lacked hypercalcemia and overt disseminated intravascular coagulation (DIC). Cytogenetic analysis additionally revealed a high hyperdiploid karyotype (52-58 chromosomes) and duplication of 1q. She was treated with a high-risk Children's Oncology Group (COG) protocol (prednisone, vincristine, daunorubicin, PEG-asparaginase), achieving a day-8 blast count < 1000/µL and complete remission with an exceptionally low flow-cytometric MRD of less than 0.01%. She underwent myeloablative allogeneic hematopoietic stem cell transplantation (HSCT) from a matched related donor and remains in complete remission(CR) more than 2 years post-transplantation. This case suggests that TCF3::HLF-positive ALL encompasses a clinical spectrum rather than a uniformly fatal disease. The absence of classic metabolic complications and the co-occurrence of high hyperdiploidy might delineate a subgroup with a better response to intensive chemotherapy and early HSCT. Larger studies integrating detailed molecular characterization are required to substantiate this hypothesis and guide risk-adapted therapy.