Patterns and Outcomes of Recurrence in Pediatric Langerhans Cell Histiocytosis.

Abstract

Background: Langerhans cell histiocytosis (LCH) is a rare neoplasm with a heterogeneous clinical spectrum ranging from isolated lesions to multisystem disease, with recurrence reported in up to 50-60% of patients. Data on outcomes of recurrent LCH from resource-limited settings remain limited.

Methods: We report a 12-year retrospective review of children (1-18 years) with biopsy-proven relapsed LCH treated between January 2014 and December 2025. Clinical characteristics, recurrence patterns, treatment, and long-term outcomes were analyzed. All patients had received first-line therapy according to LCH-III protocol. Salvage treatments included cladribine-based chemotherapy, lenalidomide-dexamethasone (Len-Dex), or surgery for isolated lesions. Follow-up was updated to December 31, 2025.

Results: Seven patients with a median age of 22 months at diagnosis (range 6-57) were included. Four had risk-organ involvement at presentation. Diabetes insipidus was present in 4/7 (57%). The median time to first recurrence was 25.8 months (range 6-104). Recurrence involved bone alone in four patients and bone with skin in three patients; none had risk-organ involvement at relapse. Three patients experienced multiple recurrences. Salvage therapy included cladribine-based chemotherapy (n = 6), Len-Dex (n = 2), and surgery (n = 1). At a median follow-up of 114 months (range 63-169), overall and event-free survival were 100%. Long-term sequelae included persistent diabetes insipidus (3/4), sclerosing cholangitis (n = 1), and sensorineural hearing loss (n = 1).

Conclusions: Children with recurrent LCH in this cohort demonstrated good long-term outcomes irrespective of the salvage treatment strategy. Len-Dex represents a feasible, cost-effective therapeutic option in resource-limited settings where access to targeted therapy is limited.