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Blood, 15 November 2007, Vol. 110, No. 10, pp. 3552-3556. Prepublished online as a Blood First Edition Paper on August 20, 2007; DOI 10.1182/blood-2007-07-100164. This Article Full Text (PDF) All Versions of this Article: blood-2007-07-100164v1 110/10/3552    most recent Alert me when this article is cited Alert me if a correction is posted 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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Klion, A. D Articles by Nutman, T. B Search for Related Content PubMed PubMed Citation Articles by Klion, A. D Articles by Nutman, T. B Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 13, 2007 Accepted July 31, 2007 Relapse following discontinuation of imatinib mesylate therapy for FIP1L1/PDGFRA-positive chronic eosinophilic leukemia: implications for optimal dosing Amy D Klion*, Jamie Robyn, Irina Maric, Weiming Fu, Laura Schmid, Steven Lemery, Pierre Noel, Melissa A Law, Marilyn Hartsell, Cheryl Talar-Williams, Michael P Fay, Cynthia E Dunbar, and Thomas B Nutman Laboratory of Parasitic Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States Laboratory of Allergic Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States Department of Laboratory Medicine,, Warren Grant Magnusson Clinical Center, National Institutes of Health, Bethesda, MD, United States Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, United States Biostatistics Research Branch, National Insitutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States * Corresponding author; email: aklion{at}niaid.nih.gov. Although imatinib is clearly the treatment of choice for FIP1L1/PDGFRA-positive chronic eosinophilic leukemia (CEL), little is known about optimal dosing, duration of treatment and the possibility of cure in this disorder. To address these questions, 5 patients with FIP1L1/PDGFRA-positive CEL with documented clinical, hematologic and molecular remission on imatinib (400 mg daily) and without evidence of cardiac involvement were enrolled in a dose de-escalation trial. The imatinib dose was tapered slowly with close followup for evidence of clinical, hematologic and molecular relapse. Two patients with endomyocardial fibrosis were maintained on imatinib 300-400 mg daily and served as controls. All 5 patients who underwent dose de-escalation, but neither of the control patients, experienced molecular relapse (p<0.05). None developed recurrent symptoms, and eosinophil counts, serum B12 and tryptase levels remained suppressed. Reinitiation of therapy at the prior effective dose led to molecular remission in all 5 patients, although 2 patients subsequently required increased dosing to maintain remission. These data are consistent with suppression rather than elimination of the clonal population in FIP1L1/PDGFRA-positive CEL and suggest that molecular monitoring may be the most useful method in determining optimal dosing without the risk of disease exacerbation. This trial was registered at www.clinicaltrials.gov as #NCT00044304. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. D. Klion How I treat hypereosinophilic syndromes Blood, October 29, 2009; 114(18): 3736 - 3741. [Abstract] [Full Text] [PDF] F. Roufosse Hypereosinophilic syndrome variants: diagnostic and therapeutic considerations Haematologica, September 1, 2009; 94(9): 1188 - 1193. [Full Text] [PDF]

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