The DOI matches its Crossref record; 12 of the 12 references it cites were found in a registry or an index.
Of mice and men: an open-label pilot study for treatment of immune thrombocytopenic purpura by an inhibitor of Syk
Abstract
To determine whether inhibition of Syk would be useful in FcγR-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 × 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 × 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).
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Citations
Cites
Immune Thrombocytopenic Purpura
Cines, D. B., & Blanchette, V. S. (2002) · New England Journal of Medicine · doi:10.1056/nejmra010501 · Cited by 1,366
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AMG 531, a Thrombopoiesis-Stimulating Protein, for Chronic ITP
Bussel, J. B., Kuter, D. J., George, J. N., McMillan, R., Aledort, L. M., Conklin, G. T., Lichtin, A. E., Lyons, R. M., Nieva, J., Wasser, J. S., et al. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa054626 · Cited by 530
Self-citationBraselmann, S., Taylor, V., Zhao, H., Wang, S., Sylvain, C., Baluom, M., Qu, K., Herlaar, E., Lau, A., Young, C., et al. (2006) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.106.109058 · Cited by 508
Self-citationChang, M., Nakagawa, P. A., Williams, S. A., Schwartz, M. R., Imfeld, K. L., Buzby, J. S., & Nugent, D. J. (2003) · Blood · doi:10.1182/blood-2002-05-1475 · Cited by 392
Chen, L., Monti, S., Juszczynski, P., Daley, J., Chen, W., Witzig, T. E., Habermann, T. M., Kutok, J. L., & Shipp, M. A. (2008) · Blood · doi:10.1182/blood-2007-07-100115 · Cited by 316
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Self-citationCrow, A. R., Song, S. M., Semple, J. W., Freedman, J. J., & Lazarus, A. H. (2001) · British Journal of Haematology · doi:10.1046/j.1365-2141.2001.03136.x · Cited by 115
Self-citationThe Effect of Antiplatelet Autoantibodies on Megakaryocytopoiesis
McMillan, R., & Nugent, D. J. (2005) · International Journal of Hematology · doi:10.1532/ijh97.04168 · Cited by 76
Immunotoxicity assessment for the novel Spleen tyrosine kinase inhibitor R406
Zhu, Y., Herlaar, E., Masuda, E. S., Burleson, G. R., Nelson, A. J., Grossbard, E. B., & Clemens, G. R. (2007) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2007.03.027 · Cited by 51
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Cited by
The SYK tyrosine kinase: A crucial player in diverse biological functions
Mócsai, A., Ruland, J., & Tybulewicz, V. L. J. (2010) · Nature Reviews Immunology · doi:10.1038/nri2765 · Cited by 1,368
Clinical updates in adult immune thrombocytopenia
Lambert, M. P., & Gernsheimer, T. B. (2017) · Blood · doi:10.1182/blood-2017-03-754119 · Cited by 445
Pathogenesis of immune thrombocytopenia
Audia, S., Mahévas, M., Samson, M., Godeau, B., & Bonnotte, B. (2017) · Autoimmunity Reviews · doi:10.1016/j.autrev.2017.04.012 · Cited by 395
Fostamatinib for the treatment of chronic immune thrombocytopenia
Connell, N. T., & Berliner, N. (2019) · Blood · doi:10.1182/blood-2018-11-852491 · Cited by 108
ADAP restraint of STAT1 signaling regulates macrophage phagocytosis in immune thrombocytopenia
Xiong, Y., Li, Y., Cui, X., Zhang, L., Yang, X., & Liu, H. (2022) · Cellular & Molecular Immunology · doi:10.1038/s41423-022-00881-2 · Cited by 27
Metadata
- Authors
- Podolanczuk, A., Lazarus, A. H., Crow, A. R., Grossbard, E., & Bussel, J. B.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2009-04-02
- Volume
- 113
- Issue
- 14
- Pages
- 3154-3160
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2095255852
- Cited by
- 263
- References
- 12
- FWCI
- 9.35
- Type
- journal article
- Language
- en
- Open access
- closed
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- Podolanczuk, A., Lazarus, A. H., Crow, A. R., Grossbard, E., & Bussel, J. B. (2009). Of mice and men: an open-label pilot study for treatment of immune thrombocytopenic purpura by an inhibitor of Syk. Blood. https://doi.org/10.1182/blood-2008-07-166439
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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