SEARCH:   Advanced

Blood, 2 April 2009, Vol. 113, No. 14, pp. 3154-3160. Prepublished online as a Blood First Edition Paper on December 18, 2008; DOI 10.1182/blood-2008-07-166439. This Article Full Text Full Text (PDF) Supplemental Table and Figure All Versions of this Article: blood-2008-07-166439v1 113/14/3154    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Podolanczuk, A. Articles by Bussel, J. B. Search for Related Content PubMed PubMed Citation Articles by Podolanczuk, A. Articles by Bussel, J. B. Related Collections Free Research Articles Platelets and Thrombopoiesis Clinical Trials and Observations Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL TRIALS AND OBSERVATIONS Of mice and men: an open-label pilot study for treatment of immune thrombocytopenic purpura by an inhibitor of Syk Anna Podolanczuk1,2, Alan H. Lazarus3, Andrew R. Crow3, Elliot Grossbard4, and James B. Bussel2 1 Department of Medicine, New York Presbyterian Hospital, Columbia University Medical Center, New York; 2 Departments of Pediatrics and Medicine, New York Presbyterian Hospital, Weill Cornell Medical Center, New York; 3 Canadian Blood Services and the Li Ka Shing Institute of St Michael's Hospital, Toronto, ON; and 4 Rigel Pharmaceuticals, South San Francisco, CA To determine whether inhibition of Syk would be useful in FcR-dependent cytopenias such as immune thrombocytopenic purpura (ITP) or autoimmune hemolytic anemia, mouse models were used to evaluate efficacy of R406, an inhibitor of Syk function, in treating cytopenia. Both disease models responded favorably to treatment, with amelioration of ITP being more dramatic. Thus, phase 2 clinical trial was initiated to study the effects of Syk inhibition in humans with ITP. Sixteen adults with chronic ITP were entered into an open-label, single-arm cohort dose-escalation trial beginning with 75 mg and escalating as high as 175 mg twice daily. Doses were increased until a persistent response was seen, toxicity occurred, or 175 mg twice daily was reached. Eight patients achieved persistent responses with platelet counts greater than 50 x 109/L (50 000 mm3) on more than 67% (actually 95%) of their study visits, including 3 who had not persistently responded to thrombopoietic agents. Four others had nonsustained responses. Mean peak platelet count exceeded 100 x 109/L (100 000 mm3) in these 12 patients. Toxicity was primarily GI-related with diarrhea (urgency) and vomiting; 2 patients had transaminitis. In conclusion, inhibition of Syk was an efficacious means of increasing and maintaining the platelet count in half the patients with chronic refractory ITP. (ClinicalTrials.gov, no. NCT00706342 [ClinicalTrials.gov] ). CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: A Syk inhibitor for sick platelets? Donna S. Woulfe Blood 2009 113: 3133-3134. [Full Text] [PDF]

	Copyright © 2009 by American Society of Hematology         Online ISSN: 1528-0020