TCF3-HLF-fusion positive acute lymphoblastic leukemia (ALL) is currently incurable. Employing an integrated approach, we uncovered distinct mutation, gene expression, and drug response profiles in TCF3-HLF-positive and treatment-responsive TCF3-PBX1-positive ALL. Recurrent intragenic deletions of PAX5 or VPREB1 were identified in constellation with TCF3-HLF. Moreover somatic mutations in the non-translocated allele of TCF3 and a reduction of PAX5 gene dosage in TCF3-HLF ALL suggest cooperation within a restricted genetic context. The enrichment for stem cell and myeloid features in the TCF3-HLF signature may reflect reprogramming by TCF3-HLF of a lymphoid-committed cell of origin towards a hybrid, drug-resistant hematopoietic state. Drug response profiling of matched patient-derived xenografts revealed a distinct profile for TCF3-HLF ALL with resistance to conventional chemotherapeutics, but sensitivity towards glucocorticoids, anthracyclines and agents in clinical development. Striking on-target sensitivity was achieved with the BCL2-specific inhibitor venetoclax (ABT-199). This integrated approach thus provides alternative treatment options for this deadly disease.

This is the largest single-center study conducted to investigate the frequency and the management strategies in patients with CHR who were treated with the same chemotherapy protocol for LGG. Premedication and desensitization were the preferred modifications in case of CHR. Overall, the success rate for carboplatin continuation is high in comparison to previous studies. Carboplatin can be continued successfully in many cases with CHR if reactions are managed in a timely fashion.

Background. Hemolytic uremic syndrome (HUS) is an acquired disorder largely affecting infants and young children. It is characterized by the triad of microangiopathic hemolytic anemia, acute renal failure, and thrombocytopenia. Although its etiology is unknown, viral and bacterial infections, disseminated malignancies in adults, and a variety of chemotherapeutic agents including cisplatin, have been implicated in its occurrence. The association of HUS with chemotherapeutic agents after its detection in a pediatric patient treated with cisplatin is reviewed. Methods. A 16‐year‐old male with osteosarcoma was treated with cisplatin as part of a chemotherapy protocol. After the fourth course, his renal function deteriorated and necessitated cessation of cisplatin. Nine months after the initiation of cisplatin, HUS developed. There was no evidence of residual tumor or metastatic disease. He received numerous packed erythrocyte and platelet transfusions for persistent hemolysis and underwent several episodes of hemodialysis. Utilizing this patient as an example, the authors reviewed the incidence of HUS developing subsequent to the use of other chemotherapeutic agents. Results. In the publishing literature, chemotherapy‐associated HUS has been described to occur 54 days to 14 months after the initiation of chemotherapeutic regimens. A variety of agents was associated with the phenomenon. Conclusion. Hemolytic uremic syndrome may be a complication of cisplatin, as evidenced by the condition that occurred in a 16‐year‐old patient with osteosarcoma after cisplatin therapy.

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Achieving lower morbidity and higher survival rates in the treatment of childhood leukemia has been a paradigm of success in modern oncology. However, serious long-term health complications occur in very large populations of childhood leukemia survivors, in the case of both acute lymphoid leukemia and acute myeloid leukemia (AML). Additionally, 15% of acute lymphoid leukemia patients have treatment failures, and rates are even higher in childhood AML. In the last few decades, as a result of well-tested experiments that statistically analyzed treatment cohorts, new agents have emerged as alternatives or supplements to established treatments, in which high survival and/or less morbidity were observed. This review provides an overview of better practice in the treatment of childhood leukemia.