title: Effectiveness of cladribine therapy in patients with pulmonary Langerhans cell histiocytosis.
abstract: BACKGROUND
  Pulmonary Langerhans cell histiocytosis (PLCH) is a rare disorder characterised by granulomatous proliferation of CD1a-positive histiocytes forming granulomas within lung parenchyma, in strong association with tobacco smoking, and which may result in chronic respiratory failure. Smoking cessation is considered to be critical in management, but has variable effects on outcome. No drug therapy has been validated. Cladribine (chlorodeoxyadenosine, 2-CDA) down-regulates histiocyte proliferation and has been successful in curbing multi-system Langerhans cell histiocytosis and isolated PLCH.
  
  
  METHODS
  We retrospectively studied 5 patients (aged 37-55 years, 3 females) with PLCH who received 3 to 4 courses of cladribine therapy as a single agent (0.1 mg/kg per day for 5 consecutive days at monthly intervals). One patient was treated twice because of relapse at 1 year. Progressive pulmonary disease with obstructive ventilatory pattern despite smoking cessation and/or corticosteroid therapy were indications for treatment. Patients were administered oral trimethoprim/sulfamethoxazole and valaciclovir to prevent opportunistic infections. They gave written consent to receive off-label cladribine in the absence of validated treatment.
  
  
  RESULTS
  Functional class dyspnea improved with cladribine therapy in 4 out of 5 cases, and forced expiratory volume in 1 second (FEV1) increased in all cases by a mean of 387 ml (100-920 ml), contrasting with a steady decline prior to treatment. Chest high-resolution computed tomography (HRCT) features improved with cladribine therapy in 4 patients. Hemodynamic improvement was observed in 1 patient with pre-capillary pulmonary hypertension. The results suggested a greater treatment effect in subjects with nodular lung lesions and/or thick-walled cysts on chest HRCT, with diffuse hypermetabolism of lung lesions on positron emission tomography (PET)-scan, and with progressive disease despite smoking cessation. Infectious pneumonia developed in 1 patient, with later grade 4 neutrocytopenia but without infection.
  
  
  CONCLUSIONS
  Data interpretation was limited by the retrospective, uncontrolled study design and small sample size.
  
  
  CONCLUSIONS
  Cladribine as a single agent may be effective therapy in patients with progressive PLCH.
authors.affiliation: National Reference Centre for Rare Pulmonary Diseases, Department of Respiratory Medicine, Louis Pradel Hospital; Claude Bernard Lyon 1 University, Lyon, UMR 754, France. vincent.grobost@gmail.com.
authors.forename: Vincent
authors.initials: V
authors.lastname: Grobost
authors.affiliation: National Reference Centre for Rare Pulmonary Diseases, Department of Respiratory Medicine, Louis Pradel Hospital; Claude Bernard Lyon 1 University, Lyon, UMR 754, France. chahera.khouatra@chu-lyon.fr.
authors.forename: Chahera
authors.initials: C
authors.lastname: Khouatra
authors.affiliation: National Reference Centre for Rare Pulmonary Diseases, Department of Respiratory Medicine, Louis Pradel Hospital; Claude Bernard Lyon 1 University, Lyon, UMR 754, France. romain.lazor@chuv.ch.|Department of Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. romain.lazor@chuv.ch.
authors.forename: Romain
authors.initials: R
authors.lastname: Lazor
authors.affiliation: National Reference Centre for Rare Pulmonary Diseases, Department of Respiratory Medicine, Louis Pradel Hospital; Claude Bernard Lyon 1 University, Lyon, UMR 754, France. jean-francois.cordier@chu-lyon.fr.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Cordier
authors.affiliation: National Reference Centre for Rare Pulmonary Diseases, Department of Respiratory Medicine, Louis Pradel Hospital; Claude Bernard Lyon 1 University, Lyon, UMR 754, France. vincent.cottin@chu-lyon.fr.|Hospices Civils de Lyon, Hôpital Louis Pradel, Centre national de référence des maladies pulmonaires rares, Centre de compétences de l'hypertension pulmonaire, Service de pneumologie, Université de Lyon, Université Claude Bernard Lyon 1, INRA, Lyon, UMR754, France. vincent.cottin@chu-lyon.fr.
authors.forename: Vincent
authors.initials: V
authors.lastname: Cottin
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017338:Cladribine / Q000627:therapeutic use*; D005260:Female; D006646:Histiocytosis, Langerhans-Cell / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy*; D006801:Humans; D008171:Lung Diseases / Q000175:diagnosis* / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012907:Smoking / Q000009:adverse effects / Q000188:drug therapy; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D017338:Cladribine