Long-term follow-up of Langerhans cell histiocytosis: 39 years' experience at a single centre.

Aim: To evaluate the long-term outcome of Langerhans cell histiocytosis (LCH) in children.

Methods: We re-evaluated all children (<15 y old at diagnosis) treated at our unit in 1962-1989. Histopathology specimens were reviewed and verified for 49 patients. Forty patients underwent physical examination and laboratory tests, and 38 were subjected to imaging, at a median time of 16 y (range 5.5-33.5) after diagnosis.

Results: Altogether, 5/49 (10%) children died, all with multi-system disease and age <2 y at diagnosis. Age at diagnosis (p=0.001) and survival (p=0.014) for the 22 children with multi-system disease was significantly lower compared with the 27 children with single-system disease. The term "maximal extent of disease" was introduced since reactivation of LCH often tends to involve additional organs not previously affected by the disease. At follow-up, late sequelae had developed in 17/40 (42%) patients, including diabetes insipidus in 6/40 (15%), CNS complications in at least 4/40 (10%) (3/16, 19%, of multi-system patients) and late-stage pulmonary disease in 4/38 (11%). Seven out of 21 (33%) of the patients with multi-system disease were alive and healthy without sequelae at follow-up, as compared to 16/24 (67%) of those with single-system disease (p=0.026). Of 14 individuals 25 y at follow-up, senior high school had been completed in 7/9 (78%) with single-system and 1/5 (20%) with multi-system disease (at maximal disease extent) (p=0.091).

Conclusion: Multi-system LCH is associated not only with increased mortality but also pronounced propensity for severe late sequelae; 51% of the patients (multi-system=33%, single-system=67%) were alive without sequelae at follow-up. Among multi-system patients, at least 19% suffered CNS sequelae.