Low-dose imatinib mesylate leads to rapid induction of major molecular responses and achievement of complete molecular remission in FIP1L1-PDGFRA-positive chronic eosinophilic leukemia

J V Jovanovic, J Score, K Waghorn, D Cilloni, E Gottardi, G Metzgeroth, P Erben, H Popp, C Walz, A Hochhaus, C Roche-Lestienne, C Preudhomme, E Solomon, J Apperley, M Rondoni, E Ottaviani, G Martinelli, F Brito-Babapulle, G Saglio, R HehlmannN C P Cross, A Reiter, D Grimwade

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189 Citations (Scopus)

Abstract

The FIP1L1-PDGFRA fusion gene is a recurrent molecular lesion in eosinophilia-associated myeloproliferative disorders, predicting a favorable response to imatinib mesylate. To investigate its prevalence, 376 patients with persistent unexplained hypereosinophilia were screened by the United Kingdom reference laboratory, revealing 40 positive cases (11%). To determine response kinetics following imatinib, real-time quantitative-polymerase chain reaction (RQ-PCR) assays were developed and evaluated in samples accrued from across the European LeukemiaNet. The FIP1L1-PDGFRA fusion transcript was detected at a sensitivity of 1 in 105 in serial dilution of the EOL-1 cell line. Normalized FIP1L1-PDGFRA transcript levels in patient samples prior to imatinib varied by almost 3 logs. Serial monitoring was undertaken in patients with a high level of FIP1L 1-PDGFRA expression prior to initiation of imatinib (100 mg/d-400 mg/d). Overall, 11 of 11 evaluable patients achieved at least a 3-log reduction in FIP1L1-PDGFRA fusion transcripts relative to the pretreatment level within 12 months, with achievement of molecular remission in 9 of 11 (assay sensitivities 1 in 10(3)-10(5)). In 2 patients, withdrawal of imatinib was followed by a rapid rise in FIP1L1-PDGFRA transcript levels. Overall, these data are consistent with the exquisite sensitivity of the FIP1L1-PDGFR alpha fusion to imatinib, as compared with BCR-ABL, and underline the importance of RO-PCR monitoring to guide management using molecularly targeted therapies
Original languageEnglish
Pages (from-to)4635 - 4640
Number of pages6
JournalBlood
Volume109
Issue number11
DOIs
Publication statusPublished - 1 Jun 2007

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