Cladribine (2-chlorodeoxyadenosine) is metabolised and phosphorylated in a cell up to
2-chloroadenosine triphosphate which is the actual effective form of the
drug. The greatest accumulation of
2-chloroadenosine triphosphate is in the most active cells, where activating (phosphorylation)
enzyme,
deoxycytidine kinase, has the highest activity, whereas inactivating
enzyme (dephosphorylation), cytoplasmic 5-nucleotidase, has the lowest activity. A very good ratio of the both
enzymes for high effectiveness of
cladribine is in resting and proliferating lymphocytes. Therefore,
cladribine is an effective medication for
hairy cell leukemia, Waldenström macroglo-bulinemia but also for
chronic -B-lymphocytic leukemia. However, such high concentrations of
2-chloroadenosine triphosphate are reached in some cells of histiocytic lines, in monocytes and also in Langerhans dendritic cells. That's why
cladribine is highly effective medication in treating
Langerhans cell histiocytosis and also in treating diseases of the
juvenile xanthogranuloma group. In the paper we present a survey of published experience with
cladribine in patients with
Langerhans cell histiocytosis. The effectiveness of
cladribine in the childhood form of
Langerhans cell histiocytosis is investigated only in 1 multicentric clinical study, other data are taken from single case reports or small series studies.
Cladribine was used in 60 adult patients altogether and in 51 of them (85%) treatment response (CR + PR) was achieved. In the group of childhood patients
cladribine was used in 182 cases and treatment response (CR + PR) was reached in 110 (60.4%) thereof. One possible explanation for a higher number of
therapy responses in adults is lower
Langerhans cell histiocytosis aggressiveness in adults than in children. Another explanation is the fact that
therapy responses in adults are summarized only from case reports and smaller cohorts, whereas in children, case reports and also results of a prospective randomized clinical study are included. Diseases of the
juvenile xanthogranuloma group are much more rare than
Langerhans cell histiocytosis and so the number of publications is smaller. In total, 7 publications describe
therapy response of
cladribine in some of the
juvenile xanthogranuloma forms (
Erdheim-Chester disease, disseminated
juvenile xanthogranuloma and localized form of plane
xanthoma type).
Cladribine was also effective in CNS infiltration by
Langerhans cell histiocytosis cells or
juvenile xanthogranuloma cells.
CONCLUSIONS: