title: Relapse following discontinuation of imatinib mesylate therapy for FIP1L1/PDGFRA-positive chronic eosinophilic leukemia: implications for optimal dosing.
abstract: 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.
authors: Laboratory of Parasitic Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD 20892, USA. aklion@nih.gov
authors: Amy D
authors: AD
authors: Klion
authors: Jamie
authors: J
authors: Robyn
authors: Irina
authors: I
authors: Maric
authors: Weiming
authors: W
authors: Fu
authors: Laura
authors: L
authors: Schmid
authors: Steven
authors: S
authors: Lemery
authors: Pierre
authors: P
authors: Noel
authors: Melissa A
authors: MA
authors: Law
authors: Marilyn
authors: M
authors: Hartsell
authors: Cheryl
authors: C
authors: Talar-Williams
authors: Michael P
authors: MP
authors: Fay
authors: Cynthia E
authors: CE
authors: Dunbar
authors: Thomas B
authors: TB
authors: Nutman
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage; D001549:Benzamides; D054316:Biomarkers, Pharmacological / Q000032:analysis; D001706:Biopsy; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D054796:Drug Dosage Calculations; D004804:Eosinophils / Q000166:cytology / Q000187:drug effects; D006801:Humans; D017681:Hypereosinophilic Syndrome / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000068877:Imatinib Mesylate; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000032:analysis / Q000235:genetics*; D010879:Piperazines / Q000008:administration & dosage*; D011743:Pyrimidines / Q000008:administration & dosage*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000032:analysis / Q000235:genetics*; D012008:Recurrence; D012074:Remission Induction; D028761:Withholding Treatment; D039221:mRNA Cleavage and Polyadenylation Factors / Q000032:analysis / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D054316:Biomarkers, Pharmacological; D015514:Oncogene Proteins, Fusion; D010879:Piperazines; D011743:Pyrimidines; D039221:mRNA Cleavage and Polyadenylation Factors; D000068877:Imatinib Mesylate; C479819:FIP1L1-PDGFRA fusion protein, human; D020796:Receptor, Platelet-Derived Growth Factor alpha
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