Recent advances in the understanding of the molecular pathogenesis and targeted therapy options in Langerhans cell histiocytosis

Langerhans cell histiocytosis (LCH) is the most common histiocytic disorder caused by the clonal expansion of myeloid precursors that differentiate into CD1a+/CD207+ cells in the lesion. Advances in genomic sequencing techniques have improved our understanding of the pathophysiology of LCH. Activation of the mitogen-activated protein kinase (MAPK) pathway is a key molecular mechanism involved in the development of LCH. Recurrent BRAF mutations and MAP2K1 mutations are the major molecular alterations involved in the activation of the MAPK pathway. Recent studies have supported the “misguided myeloid differentiation model” of LCH, where the extent of disease is defined by the differentiation stage of the cell in which the activating somatic MAPK mutation occurs, suggesting LCH. Several studies have advocated the efficacy of targeted therapy using BRAF inhibitors with a high response rate, especially in patients with high-risk or refractory LCH. However, the optimal treatment scheme for children remains unclear. This review outlines recent advances in LCH, focusing on understanding the molecular pathophysiology, emerging targeted therapy options, and their clinical implications

The role of interim-foscarnet prophylaxis in preventing cytomegalovirus infection after ex vivo αβ T cell-depleted haploidentical hematopoietic cell transplant in children

The role of interim-foscarnet prophylaxis in preventing cytomegalovirus infection after ex vivo αβ T cell-depleted haploidentical hematopoietic cell transplant in childre

Recent improvement in survival outcomes and reappraisal of prognostic factors in hepatoblastoma

Background Prognostic factors in hepatoblastoma need to be reevaluated considering the advances in treatment modalities. The study aimed to evaluate current outcomes of hepatoblastoma and reappraise the association of prognostic factors, including pre-treatment extent of tumor (PRETEXT) stage with annotation factors and Children's Hepatic tumors International Collaboration-Hepatoblastoma Stratification (CHIC-HS) system, with survival outcomes. Methods We evaluated 103 consecutive patients with hepatoblastoma retrospectively according to the treatment period based on the introduction of a liver transplantation program. Results The 5-year overall survival (OS), event-free survival (EFS), and transplant-free survival rates were 80.2%, 74.2%, and 61.8%, respectively. EFS and OS were improved significantly from 58.6% to 81.6% (P = 0.024) and from 58.6% to 90.8% (P < 0.001), respectively, in the late period (N = 74) compared with the early period (N = 29). The PRETEXT stage was significant or marginally significant for EFS and OS in the early period but not in the late period. The P, F, R, and C factors were significant for OS and EFS in the early period. However, in the late period, only the P factor was significant for OS, and the F and M factors were significant for EFS. The CHIC-HS system was significant or marginally significant for EFS in both the early and late periods; however, it was significant for OS only in the early period. Conclusion Survival rates were significantly improved in children with hepatoblastoma, especially in those with advanced PRETEXT stages with positive annotation factors and in a high-risk CHIC-HS group. Prognostic factors had different clinical implications with evolved treatment modalities