Follow-up of pediatric patients treated by IVIG for Langerhans cell histiocytosis (LCH)-related neurodegenerative CNS disease

Abstract

The follow-up of eight Japanese children with Langerhans cell histiocytosis (LCH)-related neurodegenerative central nervous system (ND-CNS) disease who were treated with intravenous immunoglobulin (IVIG) for >3 years is described. The patients developed ND-CNS disease at a median age of 5.2 (range 3.5-10.0) years and received IVIG treatment for a median duration of 6.5 + (range 3.7 to 10+) years. After a median follow-up period of 11.6 + (8.3+ to 13.9+) years after ND-CNS disease diagnosis, the median Expanded Disability Status Scale (EDSS) score of the eight patients was 4.0 (range 2.0-9.5). At the last follow-up as of March 2014, three patients have low EDSS scores (<3.0) and can walk without any assistance. Another three patients have EDSS scores of 3.5-4.5 and can walk by themselves, albeit occasionally with supports. However, the remaining two patients are wheelchair bound or bed ridden. The school performance of seven of the eight patients was below average. IVIG appeared to be most beneficial when it was administered soon after ND-CNS disease diagnosis when the EDSS scores were low (1.0-2.5). The patients who began receiving IVIG when their high EDSS scores were higher (4.5-7.0) appeared to obtain less benefit. To prevent progression of ND-CNS disease in patients with LCH, it is recommended to introduce IVIG early and to continue this therapy for >3 years.

Incidence and risk factors for clinical neurodegenerative Langerhans cell histiocytosis: a longitudinal cohort study

“…A better and reliable identification of the cND‐LCH risk population could be of major importance for initiating specific interventions very early in the course of the disease, specifically for at‐risk patients, to develop a tailored screening that combines imaging and neurocognitive assessment. Several therapeutic approaches have been attempted in ND‐LCH, including retinoic acid (Idbaih et al , ), the combination of vincristine and cytarabine (Allen et al , ), and immunoglobulin (Imashuku et al , ), and the best result that can be expected from such regimens is a stabilization of neurological symptoms. Recently, targeted therapies with BRAF inhibitors have shown efficacy in active BRAF V600E ‐mutated LCH and represent a promising approach (Haroche et al , ; Héritier et al , ).…”

Central diabetes insipidus in pediatric patients with Langerhans cell histiocytosis: Results from the JLSG‐96/02 studies

“…CDI was diagnosed based on a combination of clinical features, a water deprivation test and brain MRI findings (WITI loss of high signal intensity at the posterior pituitary lobe with or without thickened pituitary stalk). In terms of ND‐CNS, because we did not perform MRI study routinely for all LCH patients enrolled in JLSG 96 and 02 studies, we evaluated only cases of clinical ND‐CNS (cND‐CNS), as defined by our group …”

Langerhans cell histiocytosis in children: from the bench to bedside for an updated therapy

“…Neurodegenerative (ND)‐LCH may be devastating and, unfortunately, no effective therapy is available so far. The follow‐up of eight Japanese children with ND‐LCH treated with intravenous immunoglobulin (IVIG) for >3 years has been reported (Imashuku et al , ). After a median follow‐up time of 11·6 years, the median Expanded Disability Status Scale (EDSS) score of the eight patients was 4·0 (range 2·0–9·5).…”

“…IVIG appeared to be most beneficial when it was administered soon after ND‐CNS disease diagnosis when the EDSS scores were low (1·0–2·5). Based on this limited observation, to prevent progression of disease, the authors proposed that IVIG should be initiated early and continued for >3 years (Imashuku et al , ). Identification of patients in the earlier stage of ND‐LCH could thus be beneficial.…”