Clofarabine in the treatment of myelodysplastic syndromes | Aplastic Anemia & MDS International Foundation

Clofarabine in the treatment of myelodysplastic syndromes

PubMed Abstract: 
Original Publication Date: 
Thursday, February 27, 2014

Clofarabine is a potential treatment option for patients with myelodysplastic syndromes (MDS) and is well tolerated in an older patient population.  It was previously approved in 2004 for children with acute lymphocytic leukemia (ALL) who failed at least two prior treatment regimens.  It acts as an inhibitor of DNA synthesis and can reduce the percentage of leukemic blasts in adult patients with MDS and acute myeloid leukemia (AML).  Early research studies identified 40 mg/m2 daily for 5 days per course as the standard dosing regimen.


  • In a study using single-agent clofarabine, there was an overall response rate of 50% among the 6 patients with MDS. 
  • In phase II studies testing the IV and oral forms of clofarabine, a combined overall response rate of 47% was observed in 61 patients with higher-risk MDS.
  • The most frequent side-effects included bone marrow suppression, liver function abnormalities, rash, mucositis, gastrointestinal symptoms, and infection in the setting of febrile neutropenia.
  • Additional studies have demonstrated that oral clofarabine is safe and can be effective; the optimal dose and schedule are still under study.
  • Clofarabine has also been tested in combination with cytarabine (Ara-C) with responses in patients with both MDS and AML. 
  • Low-dose clofarabine may induce responses but with significant toxicity in patients with low-risk MDS who fail standard therapy, such as 5-azacytidine. 
  • Clofarabine has also been tested in combination with low-dose cytarabine in higher-risk MDS patients who have failed standard therapy.  Response rates are promising, but the role of this combination remains unclear. 


  • DNA methyltransferase inhibitors, such as azacitidine and decitabine, are standard of care for patients with MDS who require treatment; however, patients who do not respond or relapse after treatment have few treatment options.
  • Clofarabine alone and in combination with cytarabine (Ara-C) has demonstrated substantial activity against MDS and AML in elderly patients and has a favorable toxicity profile
  • Clofarabine can be used as a bridge to stem cell transplantation in patients with MDS.
  • Additional clinical trials are needed to define which patients derive the most benefit from clofarabine.
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