Long-term outcome and prognosis of mixed histiocytosis (Erdheim-Chester disease and Langerhans Cell Histiocytosis)
Francesco Pegoraro, Matthias Papo, Fleur Cohen‐Aubart, Francesco Peyronel, Gianmarco Lugli, Irene Trambusti, G. Baulier, Mathilde de Menthon, Tanguy Le Scornet, E. Oziol, Nicole Ferreira-Maldent, Olivier Hermine, Benoit Faucher, Dirk Koschel, Nicole Straetmans, Noémie Abisror, Benjamin Terrier, François Lifermann, Jérôme Razanamahery, Yves Allenbach, Jeremy Keraen, Sophie Bulifon, B. Hervier, Annamaria Buccoliero, Frédéric Charlotte, Quentin Monzani, Samia Boussouar, Natalia Shor, Annalisa Tondo, Stéphane Barète, Ahmed Idbaïh, Abdellatif Tazi, Elena Sieni, Zahir Amoura, Jean‐François Emile, Augusto Vaglio, Julien Haroche
Abstract
Background: Erdheim-Chester disease (ECD) is a rare histiocytosis that may overlap with Langerhans Cell Histiocytosis (LCH). This "mixed" entity is poorly characterized. We here investigated the clinical phenotype, outcome, and prognostic factors of a large cohort of patients with mixed ECD-LCH. Methods: This retrospective study was performed at two referral centers in France and Italy (Pitié-Salpêtrière Hospital, Paris; Meyer Children's Hospital, Florence). We included children and adults with ECD diagnosed in 2000-2022 who had biopsy-proven LCH, available data on clinical presentation, treatment and outcome, and a minimum follow-up of one year. Outcomes included differences in clinical presentation and survival between mixed ECD-LCH and isolated ECD; we also investigated response to treatments and predictors of survival in the mixed cohort. Survival was analyzed using the Kaplan-Maier method and differences in survival with the long-rank test. Cox regression models were used to evaluate the potential impact of age and gender on survival and to identify predictors of non-response and survival. Findings: = 0.948). At multivariable analysis, age at diagnosis (HR 1.052, 95% CI 1.008-1.096), associated hematologic conditions (HR 3.030, 95% CI 1.040-8.827), and treatment failure (HR 9.736, 95% CI 2.919-32.481) were associated with an increased risk of death, while lytic bone lesions with a lower risk (HR 0.116, 95% CI 0.031-0.432). Interpretation: mutation and targeted treatments are effective. Age at diagnosis, bone lesion patterns, associated hematologic conditions, and treatment failure are the main predictors of death in mixed ECD-LCH. Funding: None.