title: [Treatment of Langerhans cells histiocytosis by cladribin reached long-term complete remission in 9 out of 10 adult patients].
abstract: BACKGROUND
  The effectiveness of cladribine depends on the ratio of activating (deoxycytidine kinase) and inactivating (5-nucleotidase) enzymes. Not only is this ratio high in resting lymphocytes but also in Langerhans cells as well in some other histiocytic cells. Therefore, cladribine shows high effectiveness in patients with Langerhans cell histiocytosis (LCH). In 2003, the first report on excellent results with cladribine in first line treatment of patients with multisystem or multifocal LCH was published. That is why we use cladribine for adult patients with relapsing form of LCH and also for first line treatment of multifocal and multisystem LCH at our department.
  
  
  METHODS
  Since 2001, we have treated altogether 10 adults (9 male and 1 female) with cladribine. The median age at diagnosis was 31.5 years (range: 5-45). The multiorgan form of the disease was present in 8 patients, and 2 patients had the multifocal skeletal form with aggressive disease course. Cladribine at a dose of 5 mg/m2 SC per day was given as a 5-day course at 28-day intervals. In cases of insufficient effectiveness, in two patients after the 3rd cycle with cladribine monotherapy, we proceeded to combination therapy with cladribine of 5 mg/m2 per day, cyclophosphamide 150 mg/m2 per day and dexamethasone 20 mg per day, all on days 1-5. We planned 6 cycles at the most.
  
  
  RESULTS
  The median of cladribine cycles was 5 (range: 4-6). Altogether, 10 patients finished therapy; out of them 9 are in complete remission with the follow-up median of 26 months (range: 16-94). Treatment failure was noted only in 1 patient - in 60 days after therapy cessation the disease progressed and required further treatment (CHOEP, high-dose BEAM chemotherapy with autologous transplantation followed by Revlimid treatment and allogeneic transplantation). Treatment response - disappearance of infiltrate in the pituitary infundibulum - was observed in 2 patients with LCH affecting the pituitary infundibulum.
  
  
  CONCLUSIONS
  Cladribine is a suitable medication for multiorgan and multifocal forms of LCH. In our group of ten evaluated patients, cladribine therapy resulted in 90% of long-term complete remissions. Three patients had CNS involvement and in all three patients, treatment responses have been achieved.
authors.affiliation: Interni hematoonkologicka klinika LF MU a FN Brno, Brno. z.adam@fnbrno.cz
authors.forename: Z
authors.initials: Z
authors.lastname: Adam
authors.forename: P
authors.initials: P
authors.lastname: Szturz
authors.forename: J
authors.initials: J
authors.lastname: Duraš
authors.forename: L
authors.initials: L
authors.lastname: Pour
authors.forename: M
authors.initials: M
authors.lastname: Krejčí
authors.forename: Z
authors.initials: Z
authors.lastname: Rehák
authors.forename: R
authors.initials: R
authors.lastname: Koukalová
authors.forename: M
authors.initials: M
authors.lastname: Navrátil
authors.forename: R
authors.initials: R
authors.lastname: Hájek
authors.forename: Z
authors.initials: Z
authors.lastname: Král
authors.forename: J
authors.initials: J
authors.lastname: Mayer
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D017338:Cladribine / Q000627:therapeutic use*; D005260:Female; D006646:Histiocytosis, Langerhans-Cell / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D055815:Young Adult
chemical_list: D017338:Cladribine