Reactivation and risk of sequelae in Langerhans cell histiocytosis

OBJECTIVE: To evaluate disease reactivation in patients with Langerhans cell histiocytosis (LCH) and its impact on adverse sequelae. MATERIALS AND METHODS: A retrospective evaluation of 300 patients diagnosed with LCH between 1987 and 2002 with complete response to initial treatment was performed. RESULTS: Mean age at diagnosis was 5.3 years. With a mean follow-up of 4.8 years, reactivation of the disease occurred in 29.7% (89/300) of the patients, with two or more reactivations in 34.8% (31/89) of those. Reactivation occurred in 17.4, 36.8, 46.5, and 53.5% of the patients with single-system unifocal disease (Group A: 161 patients), single-system multifocal disease (Group B: 53 patients), multi-system disease without (Group C: 58 patients), and with (Group D: 28 patients) risk-organ involvement, respectively. The differences between the incidence rates of Groups A and B (P < 0.0004), A and C (P < 0.0001), and A and D (P < 0.0001) were highly significant. The most common reactivation sites involved were bone, middle ear, and skin; reactivation was rare in risk organs (9.5%). The median time between initial complete response and the first reactivation episode was 1 year for Group A, 1.3 years for Group B, and 9 months for Groups C and D. Most reactivation episodes (88%) occurred within the first 2 years of follow-up. Adverse sequelae were recognized in 242/300 patients: 71% (49/69) of patients with and 25.4% (44/173) without reactivations developed these adverse sequelae (P < 0.0001), respectively. Sites most commonly showing sequelae were bone, middle ear, and hypothalamus (Diabetes Insipidus). CONCLUSIONS: Incidence of reactivation correlates with the stage of the disease at diagnosis. Incidence of sequelae correlates with the occurrence of reactivations.