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Purine analoguesIn useRational designNeeds review

Cladribine

Also known as 2-chlorodeoxyadenosine, 2-CdA, Leustatin, Litak

A deoxyadenosine analogue that adenosine deaminase does not break down. The US injection label lists active hairy cell leukaemia; a 1990 report described complete remissions in 11 of 12 patients after a single seven-day infusion.

From discovery to approval

  1. 1980 · First described

    A 1980 PNAS paper tested 2-chlorodeoxyadenosine and 2-fluorodeoxyadenosine, deoxyadenosine analogues that adenosine deaminase does not break down, and found toxicity to human malignant lymphoblasts in culture and activity against mouse L1210 leukaemia. Any earlier chemical synthesis was not traced.[2][3]

  2. 1993-02-26 · FDA regular · 13 years after first description

    Leustatin (cladribine injection), NDA 020229, original approval, classed as a new molecular entity with standard review in the Drugs@FDA history; the page carries a note 'Withdrawn FR Effective 11/03/2016' and lists the product as discontinued. The original label and letter are not available there, so the indication at approval is not stated here. The type regular is an inference: no accelerated-approval wording was found. Generic cladribine injection labels list active hairy cell leukaemia.[4]

  3. 2004-04-14 · EMA regular · 24 years after first description

    Litak (cladribine, subcutaneous injection), marketing authorisation issued 14 April 2004 according to the EPAR page, which lists treatment of hairy-cell leukaemia (the page shows the current text). The page contains no conditional or exceptional-circumstances wording; the type regular is an inference. Which indications were authorised in 2004 is not stated on the page.[5]

How it works

Resistant to adenosine deaminase, it is phosphorylated inside lymphocytes and monocytes by deoxycytidine kinase and accumulates as the triphosphate. The label postulates that cells with high deoxycytidine kinase and low deoxynucleotidase activity are selectively killed.[1]

Where it came from and why

The authors write that inherited adenosine deaminase deficiency causes selective lymphopenia, possibly because toxic deoxyadenosine nucleotides accumulate in lymphocytes. They asked whether analogues that the enzyme cannot break down would be toxic to lymphocytes and lymphoid tumours.

Cancers

  • Hairy cell leukaemia

    In a 1990 series of 12 patients, all responded to a seven-day continuous infusion and 11 had complete remissions; the US injection label and the EMA page for Litak list hairy cell leukaemia.[6]

Family and partners

Drugs derived from it: Clofarabine

Worth knowing

  • Piro and colleagues report that none of the 12 patients had relapsed; the longest remission was 3.8 years and the median duration of remission was 15.5 months at the time of the report.[6]
  • The EMA page for Litak says cladribine has been in use in anticancer medicines since the 1980s and has been available as an intravenous infusion in some EU Member States since 1993; Litak is a subcutaneous injection studied in 63 adults with hairy-cell leukaemia.[5]
  • A 1983 paper found that 2-chlorodeoxyadenosine was lethal to resting normal T lymphocytes and to slowly dividing malignant T cells, unlike several other agents affecting purine metabolism.[3]
  • A 2011 review calls pentostatin and cladribine highly effective in hairy cell leukaemia, notes that their precise mechanisms in the disease are unknown, and says cladribine's additional actions may explain its greater myelosuppression.[7]

References

  1. Fresenius Kabi USA, LLC. Cladribine injection: prescribing information. DailyMed, set ID a2592a9b-bca6-4a5a-89c2-855a0634d5fe, published 14 October 2024. Read 26 October 2026. Source
  2. Carson DA, Wasson DB, Kaye J, Ullman B, Martin DW Jr, Robins RK, et al. Deoxycytidine kinase-mediated toxicity of deoxyadenosine analogs toward malignant human lymphoblasts in vitro and toward murine L1210 leukemia in vivo. Proc Natl Acad Sci U S A. 1980;77(11):6865-9. PubMedDOI
  3. Carson DA, Wasson DB, Taetle R, Yu A. Specific toxicity of 2-chlorodeoxyadenosine toward resting and proliferating human lymphocytes. Blood. 1983;62(4):737-43. PubMed
  4. U.S. Food and Drug Administration. Drugs@FDA: Approval date(s) and history, letters, labels, reviews for NDA 020229 (cladribine; Leustatin). Page read 2026-10-26. Source
  5. European Medicines Agency. Litak (cladribine): European public assessment report page (hairy-cell leukaemia; marketing authorisation issued 14/04/2004). Read 26 October 2026. Source
  6. Piro LD, Carrera CJ, Carson DA, Beutler E. Lasting remissions in hairy-cell leukemia induced by a single infusion of 2-chlorodeoxyadenosine. N Engl J Med. 1990;322(16):1117-21. PubMedDOI
  7. Johnston JB. Mechanism of action of pentostatin and cladribine in hairy cell leukemia. Leuk Lymphoma. 2011;52 Suppl 2:43-5. PubMedDOI