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intravenous solution containing 1 mg/mL in 10 mL vials
Indication: hairy cell leukaemia
Hairy cell leukaemia is a relatively uncommon type of leukaemia involving B lymphocytes. The leukaemic cells have characteristic cytoplasmic projections and infiltrate the blood and bone marrow.
Lymphocytes contain high concentrations of deoxycytidine kinase. This enzyme phosphorylates deoxyadenosine while deoxynucleotidase reverses the reaction. Cladribine is a purine analogue which passively enters cells and is phosphorylated by deoxycytidine kinase. However, the product of the reaction is resistant to deamination and accumulates as there is little deoxynucleotidase activity in lymphocytes. This causes breaks in DNA strands and leads to cell death.
Cladribine is relatively specific for lymphocytes on account of their high ratio of deoxycytidine kinase to deoxynucleotidase. In hairy cell leukaemia, a 7day infusion can induce a response rate in over 60% of patients. Previously untreated patients have a higher response rate. After complete remission, only 2 of 126 patients have relapsed during a median follow up time of 14 months.1
Inevitably, there are serious adverse effects. Myelosuppression is common with neutropenia occurring in 69% of patients, anaemia in 41% and thrombocytopenia in 14%. Infections can be fatal, but to confuse the diagnosis, patients may develop a high fever without infection. Other adverse reactions include rashes, headache, thrombosis at the infusion site, nausea and vomiting.
- Beutler E. Cladribine (2chlorodeoxyadenosine). Lancet 1992;340:952-6.