A team of researchers from Baylor College of Medicine, Texas Children’s Hospital, and UPMC Children's Hospital of Pittsburgh is calling for significant changes in the diagnosis and treatment of Langerhans cell histiocytosis (LCH). This follows extensive research analyzing LCH patients over several years.
Dr. Carl Allen, co-director of the Pediatric Cancer Program at Baylor and co-director of the Histiocytosis Program at Texas Children’s Cancer and Hematology Center, stated, "The proposed revisions are the culmination of more than a decade of work and would not have been possible without collaboration in clinical trials and translational research between scientists, patients, and families." The study reveals genetic mutations in precursor blood cells that increase the likelihood of treatment failure and LCH-associated neurodegeneration.
LCH is a rare cancer marked by the proliferation of Langerhans cells, which regulate the immune system. In LCH patients, these cells create tumors and can lead to brain-related problems due to LCH-associated neurodegeneration. Dr. Allen commented on contemporary staging approaches, noting that they "were developed at a time when the nature of LCH as a cancer was debated," highlighting the need for updated treatment methods.
Dr. Jennifer Picarsic, chief and chair of Pediatric Pathology at UPMC Children’s Hospital of Pittsburgh, added that "mutated precursor cells hiding in the bone marrow of certain LCH patients can be missed with standard histology and reported as ‘normal.’”
The study, which included 385 children and adolescents, focused on LCH's pathological features and genetic markers, such as the BRAFV600E mutation. This research supports a revised diagnostic approach for pediatric LCH, which considers these genetic drivers.
Dr. Allen noted, "In the study, we found that patients who present with a reservoir of precursor disease cells with the most common BRAFV600E mutation in bone marrow and blood are at the highest risk of treatment failure and LCH-associated neurodegeneration." These findings could pave the way for personalized treatment regimens tailored to individual patients.
This research underscores the potential for modern imaging and molecular diagnostics to improve the understanding and treatment of pediatric LCH. "This study, which includes a 15-year longitudinal cohort with correlative biology, is unprecedented," said Dr. D. Will Parsons, professor of pediatrics at Baylor.
The study was a collaboration involving multiple authors and institutions, including Baylor College of Medicine and Texas Children's Hospital. Funding support came from organizations such as the National Institutes of Health and the St. Baldrick's Foundation.
