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Molecular responses and chromosomal aberrations in patients with polycythemia vera treated with peg-proline-interferon alpha-2b

Fifty-one polycythemia vera (PV) patients were enrolled in the phase I/II clinical study PEGINVERA to receive a new formulation of pegylated interferon alpha (peg-proline-IFNα-2b, AOP2014/P1101). Peg-proline-IFNα-2b treatment led to high response rates on both hematologic and molecular levels. Hemat...

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Detalles Bibliográficos
Autores principales: Them, Nicole CC, Bagienski, Klaudia, Berg, Tiina, Gisslinger, Bettina, Schalling, Martin, Chen, Doris, Buxhofer-Ausch, Veronika, Thaler, Josef, Schloegl, Ernst, Gastl, Guenther A, Wolf, Dominik, Strecker, Karin, Egle, Alexander, Melchardt, Thomas, Burgstaller, Sonja, Willenbacher, Ella, Zagrijtschuk, Oleh, Klade, Christoph, Greil, Richard, Gisslinger, Heinz, Kralovics, Robert
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Ltd 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4657499/
https://www.ncbi.nlm.nih.gov/pubmed/25545244
http://dx.doi.org/10.1002/ajh.23928
Descripción
Sumario:Fifty-one polycythemia vera (PV) patients were enrolled in the phase I/II clinical study PEGINVERA to receive a new formulation of pegylated interferon alpha (peg-proline-IFNα-2b, AOP2014/P1101). Peg-proline-IFNα-2b treatment led to high response rates on both hematologic and molecular levels. Hematologic and molecular responses were achieved for 46 and 18 patients (90 and 35% of the whole cohort), respectively. Although interferon alpha (IFNα) is known to be an effective antineoplastic therapy for a long time, it is currently not well understood which genetic alterations influence therapeutic outcomes. Apart from somatic changes in specific genes, large chromosomal aberrations could impact responses to IFNα. Therefore, we evaluated the interplay of cytogenetic changes and IFNα responses in the PEGINVERA cohort. We performed high-resolution SNP microarrays to analyze chromosomal aberrations prior and during peg-proline-IFNα-2b therapy. Similar numbers and types of chromosomal aberrations in responding and non-responding patients were observed, suggesting that peg-proline-IFNα-2b responses are achieved independently of chromosomal aberrations. Furthermore, complete cytogenetic remissions were accomplished in three patients, of which two showed more than one chromosomal aberration. These results imply that peg-proline-IFNα-2b therapy is an effective drug for PV patients, possibly including patients with complex cytogenetic changes. Am. J. Hematol. 90:288–294, 2015. © 2014 The Authors. American Journal of Hematology published by Wiley Periodicals, Inc.