title: Cladribine (2-chlorodeoxyadenosine) in frontline chemotherapy for adult Langerhans cell histiocytosis: A single-center study of seven cases.
abstract: BACKGROUND
  Adult Langerhans cell histiocytosis is a rare disorder with diverse clinical manifestations and inconsistent treatment outcomes to conventional therapeutic regimens. Cladribine (2-chlorodeoxyadenosine) repeatedly proved effective in cases of relapsed multifocal and multisystem disease forms. In this retrospective study we present an analysis of cladribine in frontline systemic therapy.
  
  
  METHODS
  A cohort of seven male patients with biopsy proved multisystem (six cases) and multifocal (one case) Langerhans cell histiocytosis received cladribine at a dose of 5 mg/m(2) subcutaneously (five cases) or by two-hour intravenous infusion (two cases) over five consecutive days, every four weeks for a median of four courses (range 4-6). The treatment was enhanced with cyclophosphamide (300 mg intravenously on days 1-5 in cycles 4-6) and corticoids (dexamethasone 24 mg orally or methylprednisolone 250 mg intravenously on days 1-5 in cycles 4-6) in two patients, with radiotherapy (20 Gy on skin or bone lesions) in three patients and with photochemotherapy (psoralen plus ultraviolet A light, PUVA) on skin lesions in one patient.
  
  
  RESULTS
  All patients achieved clinically relevant treatment response confirmed by positron emission tomography (PET). Durable complete remissions were maintained in six patients (86%), including two patients with hypophysis involvement, with the median follow-up of 37 months (range 15-94; 49.8 ± 35.2 [ 6 ]). One patient had an aggressive, early relapsing disease requiring further treatment lines. The treatment-related toxicities consisted of transient bone marrow suppression affecting the leukocytes predominantly. Grade 3 lymphopenia occurred in five patients (71%) and grade 3 neutropenia in one patient (14%).
  
  
  CONCLUSIONS
  Cladribine, both as a single agent as well as in combination with an alkylating cytostatic and corticoids, represents an effective treatment option with favorable toxicity profile for adult patients with multisystem or aggressive multifocal form of Langerhans cell histiocytosis.
authors.affiliation: Department of Internal Medicine - Hematology and Oncology, Faculty of Medicine of Masaryk University and University Hospital Brno, Czech Republic.
authors.forename: Zdeněk
authors.initials: Z
authors.lastname: Adam
authors.forename: Petr
authors.initials: P
authors.lastname: Szturz
authors.forename: Jiří
authors.initials: J
authors.lastname: Vaníček
authors.forename: Mojmír
authors.initials: M
authors.lastname: Moulis
authors.forename: Luděk
authors.initials: L
authors.lastname: Pour
authors.forename: Marta
authors.initials: M
authors.lastname: Krejčí
authors.forename: Roman
authors.initials: R
authors.lastname: Hájek
authors.forename: Jiří
authors.initials: J
authors.lastname: Mayer
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D017338:Cladribine / Q000627:therapeutic use*; D015331:Cohort Studies; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005938:Glucocorticoids / Q000627:therapeutic use; D006646:Histiocytosis, Langerhans-Cell / Q000188:drug therapy* / Q000532:radiotherapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D010778:Photochemotherapy; D049268:Positron-Emission Tomography; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D005938:Glucocorticoids; D017338:Cladribine; D003520:Cyclophosphamide