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

doi:10.1038/leu.2008.91

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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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 JAK2^V617F 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 language	English
Pages (from-to)	965-970
Number of pages	6
Journal	Leukemia
Volume	22
Issue number	5
DOIs	https://doi.org/10.1038/leu.2008.91
State	Published - May 2008
Externally published	Yes

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@article{23ed88ec59c64be7aa44587fec5a8f98,

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

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.",

author = "A. Quint{\'a}s-Cardama and W. Tong and H. Kantarjian and D. Thomas and F. Ravandi and S. Kornblau and T. Manshouri and Cortes, {J. E.} and G. Garcia-Manero and S. Verstovsek",

note = "Funding Information: This work was supported by The University of Texas MD Anderson Cancer Center{\textquoteright}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).",

year = "2008",

month = may,

doi = "10.1038/leu.2008.91",

language = "English",

volume = "22",

pages = "965--970",

journal = "Leukemia",

issn = "0887-6924",

publisher = "Springer Nature",

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T1 - A phase II study of 5-azacitidine for patients with primary and post-essential thrombocythemia/polycythemia vera myelofibrosis

AU - Quintás-Cardama, A.

AU - Tong, W.

AU - Kantarjian, H.

AU - Thomas, D.

AU - Ravandi, F.

AU - Kornblau, S.

AU - Manshouri, T.

AU - Cortes, J. E.

AU - Garcia-Manero, G.

AU - Verstovsek, S.

N1 - Funding Information: 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).

PY - 2008/5

Y1 - 2008/5

N2 - 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.

AB - 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.

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DO - 10.1038/leu.2008.91

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AN - SCOPUS:43749117734

SN - 0887-6924

VL - 22

SP - 965

EP - 970

JO - Leukemia

JF - Leukemia

IS - 5

ER -

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

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