Universität zu Köln

Jamieson, Catriona, Hasserjian, Robert, Gotlib, Jason, Cortes, Jorge ORCID: 0000-0002-8636-1071, Stone, Richard, Talpaz, Moshe ORCID: 0000-0003-3361-3981, Thiele, Juergen, Rodig, Scott and Pozdnyakova, Olga (2015). Effect of treatment with a JAK2-selective inhibitor, fedratinib, on bone marrow fibrosis in patients with myelofibrosis. J. Transl. Med., 13. LONDON: BMC. ISSN 1479-5876

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Abstract

Background: Progressive bone marrow fibrosis (BMF) is a cardinal feature of many myeloproliferative neoplasms (MPNs) and there is a documented association between the severity of BMF and overall prognosis. We conducted an exploratory analysis of sequential BMF data from two phase I studies of long-term treatment with the Janus kinase 2 (JAK2) inhibitor fedratinib in patients with myelofibrosis. Methods: Bone marrow samples were obtained at baseline and after every six cycles (24 weeks) of daily fedratinib treatment. Fibrosis was centrally assessed by three independent haematopathologists, who were blinded to the patients' data, and graded according to European Consensus Myelofibrosis Grading Criteria. The analysis population comprised patients with a baseline BMF grade >= 1, and at least one post-baseline BMF grade assessment. Changes in BMF grade compared with baseline were classified as improvement (>= 1 grade reduction), stabilisation (no change in any baseline BMF grade <3) or worsening (>= 1 grade increase). Results: Twenty-one patients were included in the analysis. A total of 153 bone marrow samples were analysed. Improvement or stabilisation of BMF from baseline was recorded in 15 of 18 (83 %) evaluable patients at cycle 6 and in four of nine (44 %) evaluable patients at cycle 30. Two patients achieved resolution of their BMF (grade = 0) by cycle 12. Conclusions: This exploratory analysis indicates that improvement or even resolution of BMF may be achievable with JAK2 inhibitor therapy in some patients with MPNs and myelofibrosis.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Jamieson, Catriona UNSPECIFIED UNSPECIFIED UNSPECIFIED Hasserjian, Robert UNSPECIFIED UNSPECIFIED UNSPECIFIED Gotlib, Jason UNSPECIFIED UNSPECIFIED UNSPECIFIED Cortes, Jorge UNSPECIFIED orcid.org/0000-0002-8636-1071 UNSPECIFIED Stone, Richard UNSPECIFIED UNSPECIFIED UNSPECIFIED Talpaz, Moshe UNSPECIFIED orcid.org/0000-0003-3361-3981 UNSPECIFIED Thiele, Juergen UNSPECIFIED UNSPECIFIED UNSPECIFIED Rodig, Scott UNSPECIFIED UNSPECIFIED UNSPECIFIED Pozdnyakova, Olga UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-393056
DOI:	10.1186/s12967-015-0644-4
Journal or Publication Title:	J. Transl. Med.
Volume:	13
Date:	2015
Publisher:	BMC
Place of Publication:	LONDON
ISSN:	1479-5876
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CHRONIC IDIOPATHIC MYELOFIBROSIS; INTERNATIONAL-WORKING-GROUP; POLYCYTHEMIA-VERA; MYELOPROLIFERATIVE NEOPLASMS; ESSENTIAL THROMBOCYTHEMIA; RETICULIN FIBROSIS; MYELOID METAPLASIA; EUROPEAN CONSENSUS; JAK2; MUTATION Multiple languages Medicine, Research & Experimental Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/39305