A phase II study of 5-azacitidine for patients with primary and post-essential thrombocythemia/polycythemia vera myelofibrosis

A. Quintás-Cardama, W. Tong, H. Kantarjian, D. Thomas, F. Ravandi, S. Kornblau, T. Manshouri, J. E. Cortes, G. Garcia-Manero, S. Verstovsek

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96 Scopus citations

Abstract

Myelofibrosis (MF; primary or post-essential thrombocythemia/ polycythemia vera) is incurable clonal myeloproliferative disorder, with no effective treatment. Epigenetic changes play an important role in cancer pathogenesis through transcriptional silencing of critical tumor suppressor genes. We conducted a phase-II study to evaluate the activity of DNA methyltransferase inhibitor, 5-azacitidine, in patients with MF. Thirty-four patients (76% previously treated) received 5-azacitidine at 75mg/m2 subcutaneously daily for 7 days, every 4 weeks. Twelve (35%) patients had abnormal cytogenetics and 19 (70%) of 27 evaluable patients had JAK2V617F mutation. Responses occurred in 8 (24%) patients after a median of 5 months (range, 3-10). Partial response occurred in 1 (3%) patient (duration 22+ months) and clinical improvement in 7 (21%) patients (median duration 4 months; range, 2-8.5). Myelosuppression was the major adverse effect, with grade 3-4 neutropenia in 10 (29%) patients. Global DNA methylation assessed by the long interspersed nucleotide element (LINE) bisulfite/pyrosequencing assay decreased from 53% pretherapy to 44% on day 14 (P = 0.0014) and returned to 50% at the end of the first 28-day cycle (P = 0.016). 5-azacitidine is relatively well tolerated and results in induction of global hypomethylation in patients with MF, but results in limited clinical activity.

Original languageEnglish (US)
Pages (from-to)965-970
Number of pages6
JournalLeukemia
Volume22
Issue number5
DOIs
StatePublished - May 2008
Externally publishedYes

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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    Quintás-Cardama, A., Tong, W., Kantarjian, H., Thomas, D., Ravandi, F., Kornblau, S., Manshouri, T., Cortes, J. E., Garcia-Manero, G., & Verstovsek, S. (2008). A phase II study of 5-azacitidine for patients with primary and post-essential thrombocythemia/polycythemia vera myelofibrosis. Leukemia, 22(5), 965-970. https://doi.org/10.1038/leu.2008.91