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Chronic Myeloproliferative Disorders

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

Leukemia volume 22, pages 965–970 (2008)Cite this article

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 75 mg/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.

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Acknowledgements

This work was supported by The University of Texas MD Anderson Cancer Center's Physician Scientist Program Award funded by the Commonwealth Cancer Foundation for Research, by The Leukemia and Lymphoma Society of America, and by NIH Grants CA100067 and CA105771 (all to G G-M).

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  1. Department of Leukemia, MD Anderson Cancer Center, The University of Texas, Houston, TX, USA

    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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  1. A Quintás-Cardama
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Correspondence to S Verstovsek.

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Quintás-Cardama, A., Tong, W., Kantarjian, H. et al. A phase II study of 5-azacitidine for patients with primary and post-essential thrombocythemia/polycythemia vera myelofibrosis. Leukemia 22, 965–970 (2008). https://doi.org/10.1038/leu.2008.91

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