Treatment of Langerhans Cells Histiocytosis by Cladribin Reached Long-Term Complete Remission in 9 out of 10 Adult Patients

Authors: Z. Adam 1;  P. Szturz 1;  J. Ďuraš 2;  L. Pour 1;  M. Krejčí 1;  Z. Řehák 3;  R. Koukalová 3;  M. Navrátil 1;  R. Hájek 1;  Z. Král 1;  J. Mayer 1
Authors‘ workplace: Interní hematoonkologická klinika, LF MU a FN Brno 1;  Ústav klinické hematologie, FN Ostrava 2;  Oddělení nukleární medicíny, centrum PET, MOÚ Brno 3
Published in: Klin Onkol 2012; 25(4): 255-261
Category: Original Articles


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. 

Patients and 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. 

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. 

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.

Key words:
cladribine – 2-chlorodeoxyadenosine – Langerhans cell histiocytosis – diabetes insipidus

This study was supported by grant of Internal Grant Agency of the Czech Ministry of Health NT 12215-4, grants of the Czexh Ministry of Education, Youth and Sports MSM0021622434, LC06027, grants of Internal Grant Agency of the Czech Ministry of Health NT11154, NT12130, NT12215 and NS10408.

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE “uniform requirements” for biomedical papers.

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28. 10. 2011


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