Long‐term complications in uniformly treated paediatric Langerhans histiocytosis patients disclosed by 12 years of follow‐up of the JLSG‐96/02 studies

Abstract

Summary Langerhans cell histiocytosis (LCH) is a rare inflammatory myeloid neoplasia derived from immature myeloid dendritic cells with the mitogen‐activated protein kinase (MAPK) pathway gene mutation. LCH is rarely fatal, but patients develop various permanent consequences (PCs). We report the frequencies of LCH‐related PCs in paediatric patients (n = 317) treated by the JLSG‐96/02 AraC‐containing regimens. One‐third of LCH patients had at least one PC at a median follow‐up of 12 years. Central nervous system (CNS)‐related PCs (neurological and endocrinological) accounted for 21·5%, non‐CNS‐related 16·7%. We require novel therapeutic measures to further reduce the frequency of LCH‐related PCs.

Pilot study to estimate the safety and effectiveness of hydroxyurea and methotrexate recurrent langerhans cell histiocytosis (LCH-HU-pilot)

“…PD is defined as the worsening of signs or symptoms due to LCH and/or the appearance of new LCH lesions. 12,24,32,40, and 48 weeks after hydroxyurea administration. Treatment response at these time points after hydroxyurea administration is evaluated as follows.…”

“…[ 10 ] The most significant risk factor for permanent central nervous system consequences, such as central diabetes insipidus, anterior pituitary hormone deficiency, and neurodegenerative disease is a relapse of LCH. [ 11 , 12 ]…”

“…[10] The most significant risk factor for permanent central nervous system consequences, such as central diabetes insipidus, anterior pituitary hormone deficiency, and neurodegenerative disease is a relapse of LCH. [11,12] Zinn et al recently reported that hydroxyurea, which has previously been shown to be effective in the treatment of myeloid neoplasms (chronic myelogenous leukemia, polycythemia vera, and essential thrombocytosis) and sickle cell disease (SCD), is also effective in the treatment of LCH . [13] In this report, fifteen recurrent or refractory LCH cases (13 adult cases and 2 childhood cases) involving the skin and bone with or without lymph node involvement were treated with hydroxyurea.…”

New biomarker paves the way for a clinical trial for neurodegeneration in Langerhans cell histiocytosis

“…4 At 10 years after the diagnosis of LCH, the incidence of clinical ND is 5% in total and more than 10% in patients with cDI. 5 Since ND-LCH usually develops long after the diagnosis of LCH, after the initial LCH lesions have healed, there may be cases of progressive cerebellar ataxia of unknown origin being followed in neurology without being noticed as ND-LCH. Therefore, the actual incidence of ND-LCH could increase.…”

“…Patients who have disease involvement of the mastoid, temporal, and orbital bones and have developed central diabetes insipidus (cDI) are at high risk for developing ND‐LCH 4 . At 10 years after the diagnosis of LCH, the incidence of clinical ND is 5% in total and more than 10% in patients with cDI 5 . Since ND‐LCH usually develops long after the diagnosis of LCH, after the initial LCH lesions have healed, there may be cases of progressive cerebellar ataxia of unknown origin being followed in neurology without being noticed as ND‐LCH.…”