Azacitidine in fludarabine-refractory chronic lymphocytic Leukemia: A phase II study

Asifa Malik, Mahran Shoukier, Guillermo Garcia-Manero, William Wierda, Jorge Cortes, Susan Bickel, Michael J. Keating, Zeev Estrov

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


Background: Treatment of fludarabine-refractory disease in patients with chronic lymphocytic leukemia (CLL) remains a challenge. Because a recent genome-wide methylation analysis of CLL cells suggested that demethylation therapy might be beneficial in CLL, we conducted a phase II trial with the hypomethylating agent azacitidine in patients with recurrent fludarabine-refractory CLL. Patients and Methods: Nine patients with recurrent fludarabine-refractory Rai stage IV CLL (median age, 74 years; range, 49-81 years) were enrolled. Azacitidine (75 mg/m2) was administered by subcutaneous injection daily for 7 consecutive days every 3 to 8 weeks, and the data were analyzed at a median follow-up of 9 months (range 3-47 months). Results: The trial was prematurely discontinued because of lack of response and slow accrual. The number of cycles administered ranged from 1 to 6. Three patients received 1 cycle, 3 patients received 2 cycles, and the remaining 3 patients received 4, 5, or 6 cycles. Side effects included grade 2 or 3 infectious episodes (resulting from immunosuppression and drug-induced neutropenia), diarrhea, rash, vomiting, anemia, and thrombocytopenia. One patient experienced reduction of hepatosplenomegaly and a substantial increase in platelet count after 4 cycles of therapy. However this response did not qualify as a partial response according to the National Cancer Institute International Workshop on CLL (NCI-IWCLL) criteria. At a median follow-up of 9 months after the start of azacitidine treatment, 3 patients (33%) who went on to receive other treatments were alive. Conclusions: Although no partial or complete responses occurred in these heavily pretreated patients, the encouraging response in 1 of these patients may warrant further studies to investigate the effects of azacitidine in CLL.

Original languageEnglish (US)
Pages (from-to)292-295
Number of pages4
JournalClinical Lymphoma, Myeloma and Leukemia
Issue number3
StatePublished - Jun 2013
Externally publishedYes


  • Azacitidine
  • Chronic lymphocytic leukemia
  • DNA methylation

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research


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