Childhood Langerhans cell histiocytosis with severe lung involvement: a nationwide cohort study

Abstract

Background: Lung involvement in childhood Langerhans cell histiocytosis (LCH) is infrequent and rarely life threatening, but occasionally, severe presentations are observed.

Methods: Among 1482 children (< 15 years) registered in the French LCH registry (1994-2018), 111 (7.4%) had lung involvement. This retrospective study included data for 17 (1.1%) patients that required one or more intensive care unit (ICU) admissions for respiratory failure.

Results: The median age was 1.3 years at the first ICU hospitalization. Of the 17 patients, 14 presented with lung involvement at the LCH diagnosis, and 7 patients (41%) had concomitant involvement of risk-organ (hematologic, spleen, or liver). Thirty-five ICU hospitalizations were analysed. Among these, 22 (63%) were secondary to a pneumothorax, 5 (14%) were associated with important cystic lesions without pneumothorax, and 8 (23%) included a diffuse micronodular lung infiltration in the context of multisystem disease. First-line vinblastine-corticosteroid combination therapy was administered to 16 patients; 12 patients required a second-line therapy (cladribine: n = 7; etoposide-aracytine: n = 3; targeted therapy n = 2). A total of 6 children (35%) died (repeated pneumothorax: n = 3; diffuse micronodular lung infiltration in the context of multisystem disease: n = 2; following lung transplantation: n = 1). For survivors, the median follow-up after ICU was 11.2 years. Among these, 9 patients remain asymptomatic despite abnormal chest imaging.

Conclusions: Severe lung involvement is unusual in childhood LCH, but it is associated with high mortality. Treatment guidelines should be improved for this group of patients: viral infection prophylaxis and early administration of a new LCH therapy, such as targeted therapy.

Keywords: Childhood; Intensive care; Langerhans cell histiocytosis; Pulmonary; Severe; Targeted therapy.

Fig. 1

Chest CT scan images (lung window). Initial images of PLCH for 12 of 17 patients. PLCH: Pulmonary Langerhans cell histiocytosis

Fig. 2

Intensive care unit (ICU) hospitalizations and management for 17 patients with pulmonary Langerhans cell histiocytosis. Solid bars represent one ICU stay, and the length of stay is proportional to the scale bar (each section on the X-axis = 20 days). Bracketed numbers are the number of days between ICU stays. □ indicates death. Pulmonary lesions associated with respiratory failure are indicated with shading (black: pneumothorax; dark grey: severe cystic lung lesion without pneumothorax; light grey: diffuse micronodular lung infiltration). Anti-LCH treatments are specified above each ICU stay, and the treatment time is indicated with lines (VC: vinblastine corticosteroid; VP16 Ara-C: Etoposide-Cytarabine; 2CDA: Cladribine; Mek i: MEK inhibitor; BRAF i: BRAF inhibitor). Points before or following the lines indicate ongoing treatments for unspecified times. Pneumothorax treatments are indicated under each ICU stay (D: drainage, T: talcage, P: pleurectomy by thoracotomy)

Fig. 3

Chest CT scan images (lung window) before and after initiation of target therapy. Images show lungs before and after the initiation of a BRAF-kinase inhibitor (Vemurafenib) and a MEK inhibitor (Cobimetinib)

Fig. 4

Overall survival after pulmonary Langerhans cell histiocytosis diagnosis for patients with severe lung involvement (n = 17)