Cladribine improves lung cysts and pulmonary function in a child with histiocytosis

Epaud, Ralph; Pointe, Hubert Ducou Le; Fasola, Sylvie; Ploussard, Sandra; Delestrain, Céline; Sileo, Chiara; Donadieu, Jean

doi:10.1183/09031936.00146114

Cited by 23 publications

(21 citation statements)

References 13 publications

(14 reference statements)

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“…Here, we found that vinblastine + steroids had either no effect or did not preclude further lung function deterioration in patients with lung involvement. For these patients, cladribine is a promising treatment [28–30]. …”

Section: Discussionmentioning

confidence: 99%

Vinblastine chemotherapy in adult patients with langerhans cell histiocytosis: a multicenter retrospective study

Tazi

Lorillon

Haroche

et al. 2017

Orphanet J Rare Dis

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BackgroundVinblastine is the standard treatment for children with Langerhans cell histiocytosis (LCH). Whether this treatment could be extended to adults with LCH is questionable. This retrospective multicenter study included 35 adult patients (median age 33 years; 23 men; 80% with multisystem LCH) who were treated with vinblastine + steroids as a first-line chemotherapy and followed for a median time of 83 months. The objectives were to determine the overall response rate (based on the Histiocyte Society criteria), disease reactivation rate, toxicity, permanent consequences, and survival rate corresponding to this treatment. The lung involvement outcome was based on serial lung function tests. The distribution of right-censored end points was estimated by the Kaplan-Meier method. Univariate Cox model with time-fixed and time-varying covariates was used for the predictive analysis of reactivation in the responders. Univariate analyses of risk factors for neurotoxicity were based on nonparametric Wilcoxon rank sum tests and exact Fisher tests.ResultsThe median duration of the first course of vinblastine was 7.6 months, with a median cumulative dose of 160 mg [IQR 120–212]. Seventy percent of the patients were responders at the end of this treatment. Subsequently, LCH reactivation occurred with a 5-year cumulative incidence of 40%. During the study, 27 reactivations were observed in 17 patients, and half of these episodes were retreated with vinblastine. At the end of the last vinblastine treatment, 70% of the patients were responders. None of the patients with impaired lung function improved. No grade 3–4 peripheral neuropathy was observed. At the final vinblastine treatment, permanent LCH consequences, primarily pituitary stalk involvement, were present in 15 (43%) patients, and all were present at the time of vinblastine initiation. The 10-year survival rate was 86.2% (95CI, 71.8–100%), and the 2 patients who died from LCH had risk organ localizations.ConclusionsVinblastine is an effective and well-tolerated first-line treatment for adult LCH except in patients with lung involvement and impaired lung function. However, a significant portion of patients experienced LCH reactivation during long-term follow up. As in childhood LCH, the presence of risk organ involvement has a negative impact on patient prognosis.

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Section: Discussionmentioning

confidence: 99%

Vinblastine chemotherapy in adult patients with langerhans cell histiocytosis: a multicenter retrospective study

Tazi

Lorillon

Haroche

et al. 2017

Orphanet J Rare Dis

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“…[79][80][81] It is directly toxic to monocytes and lymphocytes and can induce remission or improve pulmonary function in PLCH. [81][82][83][84][85][86][87] A phase II clinical trial investigating the safety and efficacy of cladribine in PLCH is currently underway (NCT01473797, www.ClinicalTrials.gov).…”

Section: Pharmacological Treatmentmentioning

confidence: 99%

Pulmonary Langerhans Cell Histiocytosis

Shaw

Borchers

Zander

et al. 2020

Semin Respir Crit Care Med

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Pulmonary Langerhans cell histiocytosis (PLCH) is a diffuse cystic lung disease that is strongly associated with exposure to cigarette smoke. Recently, activating pathogenic mutations in the mitogen-activated protein kinase pathway have been described in the dendritic cells in patients with PLCH and have firmly established PLCH to be an inflammatory myeloid neoplasm. Disease course and prognosis in PLCH are highly variable among individual patients, ranging from spontaneous resolution to development of pulmonary hypertension and progression to terminal respiratory failure. A subset of patients with PLCH may have extrapulmonary involvement, typically involving the skeletal system in the form of lytic lesions, skin lesions, or the central nervous system most commonly manifesting in the form of diabetes insipidus. Smoking cessation is the cornerstone of treatment in patients with PLCH and can lead to disease regression or stabilization in a substantial proportion of patients. Further insight into the underlying molecular pathogenesis of PLCH has paved the way for the future development of disease-specific biomarkers and targeted treatment options directed against the central disease-driving mutations.

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“…Basing on extrapolated observations made during randomised trials in children, various types of cytoreductive therapy (methotrexate, vinblastine, 6 mercaptopurine, etoposide) have been applied in adult LCH patients [3,[42][43][44][45][46][47][48][49]. However, the disease in adults runs a diverse clinical course and many drugs are differently tolerated.…”

Section: Chemotherapymentioning

confidence: 99%

Pulmonary Langerhans' Cell Histiocytosis in Adults

Radzikowska¹

2017

Advances in Respiratory Medicine

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Pulmonary Langerhans' cell histiocytosis (PLCH) is a rare disorder of unknown cause characterised by the infiltration of the lungs and other organs by the bone marrow derived Langerhans' cells, which carry mutations of BRAF gene and/or NRAS, KRAS and MAP2K1 genes. It occurs predominantly in young smokers, without gender predominance. The disease is characterised by formation of eosinophilic granulomas with the presence of Langerhans' cells infiltrating and destroying distal airways. High-resolution computed tomography of the chest (HRCT) plays an outstanding role in PLCH diagnosis. The typical radiological picture of PLCH is the presence of small intralobular nodules, often forming 'tree in bud' lesions, cavitated nodules, thin-and thick-walled cystic lesions frequently confluent. Definite diagnosis requires the finding of characteristic lesions in histological examination and demonstration of antigen CD1a or CD207 presenting cells in immunohistochemistry. Smoking cessation is the most important recommendation for PLCH patients. There are no evidence based data regarding systemic steroid therapy. The treatment of progressive PLCH is based on cladribine or cytarabine as salvage therapy. The prognosis is good, and over 85% of patients survive 10 years.

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Cladribine improves lung cysts and pulmonary function in a child with histiocytosis

Cited by 23 publications

References 13 publications

Vinblastine chemotherapy in adult patients with langerhans cell histiocytosis: a multicenter retrospective study

Vinblastine chemotherapy in adult patients with langerhans cell histiocytosis: a multicenter retrospective study

Pulmonary Langerhans Cell Histiocytosis

Pulmonary Langerhans' Cell Histiocytosis in Adults

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