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, Thomas B. Nutman

Research output: Contribution to journalArticle

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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 deescalation, 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.

Original languageEnglish (US)
Pages (from-to)3552-3556
Number of pages5
JournalBlood
Volume110
Issue number10
DOIs
StatePublished - Nov 15 2007
Externally publishedYes

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Recurrence
Tryptases
Therapeutics
Endomyocardial Fibrosis
Eosinophils
Disease Progression
Pdgfra-Associated Chronic Eosinophilic Leukemia
Imatinib Mesylate
Monitoring
Serum
Population

ASJC Scopus subject areas

  • Hematology

Cite this

Relapse following discontinuation of imatinib mesylate therapy for FIP1L1/PDGFRA-positive chronic eosinophilic leukemia : Implications for optimal dosing. / Klion, Amy D.; Robyn, Jamie; Maric, Irina; Fu, Weiming; Schmid, Laura; Lemery, Steven; Noel, Pierre; Law, Melissa A.; Hartsell, Marilyn; Talar-Williams, Cheryl; Fay, Michael P.; Dunbar, Cynthia E.; Nutman, Thomas B.

In: Blood, Vol. 110, No. 10, 15.11.2007, p. 3552-3556.

Research output: Contribution to journalArticle

Klion, AD, Robyn, J, Maric, I, Fu, W, Schmid, L, Lemery, S, Noel, P, Law, MA, Hartsell, M, Talar-Williams, C, Fay, MP, Dunbar, CE & Nutman, TB 2007, 'Relapse following discontinuation of imatinib mesylate therapy for FIP1L1/PDGFRA-positive chronic eosinophilic leukemia: Implications for optimal dosing', Blood, vol. 110, no. 10, pp. 3552-3556. https://doi.org/10.1182/blood-2007-07-100164
Klion, Amy D. ; Robyn, Jamie ; Maric, Irina ; Fu, Weiming ; Schmid, Laura ; Lemery, Steven ; Noel, Pierre ; Law, Melissa A. ; Hartsell, Marilyn ; Talar-Williams, Cheryl ; Fay, Michael P. ; Dunbar, Cynthia E. ; Nutman, Thomas B. / Relapse following discontinuation of imatinib mesylate therapy for FIP1L1/PDGFRA-positive chronic eosinophilic leukemia : Implications for optimal dosing. In: Blood. 2007 ; Vol. 110, No. 10. pp. 3552-3556.
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