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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.
CLINICAL TRIALS AND OBSERVATIONS Relapse following discontinuation of imatinib mesylate therapy for FIP1L1/PDGFRA-positive chronic eosinophilic leukemia: implications for optimal dosing1 Laboratory of Parasitic Diseases, National Institutes of Allergy and Infectious Diseases (NIAID), 2 Hematology Branch, National Heart, Lung and Blood Institute (NHLBI); 3 Laboratory of Allergic Diseases, NIAID; 4 Department of Laboratory Medicine, Warren Grant Magnusson Clinical Center; and 5 Biostatistics Research Branch, NIAID, National Institutes of Health (NIH), Bethesda, MD 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 follow-up for evidence of clinical, hematologic, and molecular relapse. Two patients with endomyocardial fibrosis were maintained on imatinib 300 to 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 < .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 http://www.clinicaltrials.gov as no. NCT00044304 [ClinicalTrials.gov] .
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