Cladribine (Litak, Leustat) for leukaemia: reports of progressive multifocal encephalopathy (PML); stop treatment if PML suspected

Consider progressive multifocal encephalopathy (PML) in the differential diagnosis for patients with new or worsening neurological signs or symptoms, even several years after treatment with cladribine.

Advice for healthcare professionals:

  • we are aware of 3 confirmed cases of progressive multifocal encephalopathy (PML) worldwide that developed 6 months to several years after patients received treatment with cladribine for haematological conditions
  • an association between cladribine and prolonged lymphopenia has been reported
  • consider PML in the differential diagnosis for patients with new or worsening neurological signs or symptoms
  • if PML is suspected, stop cladribine treatment immediately and ensure the patient receives specialist investigation
  • patients should be monitored for signs and symptoms or appearance of new neurological dysfunction (eg, motor, cognitive, or psychiatric symptoms)
  • although reports are very infrequent, PML is a life-threatening neurological disorder; advise patients of symptoms of PML and the need to get medical help immediately if these occur


The following cladribine medicines are licensed in the UK:

  • Litak, indicated for hairy cell leukaemia

  • Leustat, indicated for hairy cell leukaemia and B-cell chronic lymphocytic leukaemia

  • Mavenclad, recently authorised for highly active relapsing-remitting multiple sclerosis

Reports of PML in oncology indications

A recent European review was triggered by post-marketing reports of progressive multifocal encephalopathy (PML) in patients given cladribine for haematological cancer. As of March 2017, 3 confirmed reports of PML (including at least 1 fatal case) have been reported in patients worldwide taking cladribine for various haematological conditions. None of these reports were from patients in the UK.

Since cladribine can induce myelosuppression and immunosuppression, as well as lymphopenia that can last several months, it is thought to be biologically plausible that it could increase the risk of PML. An association between cladribine and prolonged lymphopenia has been reported.

For cladribine medicines with oncology indications (Litak and Leustat), the product information for healthcare professionals and patients is being updated and a letter has been sent to haematologists and oncologists about the risk.

PML in multiple sclerosis indication

The product information for cladribine for the multiple sclerosis indication already includes a warning about the risk of PML. A Prescriber’s Guide is available.

About PML

PML is a rare, progressive, and demyelinating disease of the central nervous system that can be fatal. It is caused by activation of JC virus, which usually remains latent and typically only causes PML in immunocompromised patients. The factors leading to activation of the latent infection are not fully understood. If PML is suspected, investigations may include magnetic resonance imaging, ultrasensitive polymerase chain reaction (PCR) assay for JC virus DNA, or brain biopsy for JC virus.

Reporting of suspected adverse reactions

Suspected adverse reactions should be reported to us on a Yellow Card, even if some time has passed since administration.

Article citation: Drug Safety Update volume 11, issue 5; December 2017: 2.

Post-publication note:

In March 2022, links were updated during routine review of older articles.

Published 14 December 2017