A team of researchers from Baylor College of Medicine, Texas Children’s Hospital, and UPMC Children's Hospital of Pittsburgh has suggested a significant change in the diagnosis and treatment methods for Langerhans cell histiocytosis (LCH). After several years of study, the team has concluded that changes in genetic makeup of precursor blood cells in LCH patients can forecast a highly increased risk of treatment failure and development of associated neurodegeneration. Dr. Carl Allen, co-author of the study and co-director of various programs at Baylor and Texas Children’s Cancer and Hematology Center, emphasized the importance of collaboration in reaching this breakthrough.
“This study identifies genetic changes in a type of precursor blood cell that predict a much higher chance of treatment failure and risk of developing LCH-associated neurodegeneration,” said Allen.
LCH is a rare form of cancer that causes the abnormal accumulation of immune cells known as Langerhans cells, forming tumors in organs. Sometimes these cells cause neurodegeneration by migrating to the brain. The current method of treatment involves chemotherapy, which Allen stated, "ultimately cures fewer than half and has little effect on LCH-associated neurodegeneration."
Dr. Jennifer Picarsic, chief of Pediatric Pathology at UPMC Children's Hospital, discussed another major finding from the study, explaining that mutated precursor cells in the bone marrow of some patients can remain undetected with standard testing, leading to misdiagnoses.
The research, involving 385 young patients over 17 years, matched outcomes with the stage of LCH, mutations, and the BRAFV600E mutation's presence in bodily cells before treatment began. Findings published in the journal Blood advocate for revising pediatric LCH diagnostic stages considering these genetic factors. Allen pointed out that patients with the BRAFV600E mutation in their bone marrow and blood were at the greatest risk.
Addressing this, the study also underscored the potential for modified testing and treatment options—strategies that could be more personalized based on individual risks. Current clinical techniques supported by sensitive molecular diagnostics offer a chance to improve risk evaluation for LCH.
Dr. D. Will Parsons noted the study's unprecedented scope and impact, highlighting the 15-year longitudinal cohort's potential for immediate changes and future patient care implications. He also noted that the research benefitted significantly from longstanding collaborations with Dr. Miriam Merad's team at the Icahn School of Medicine at Mount Sinai and other institutions.
The research was supported by various institutions and funding bodies, including the National Institutes of Health, the Department of Defense, and numerous foundations dedicated to cancer research and treatment improvements. For full funding details, refer to the published article.
