|
|
Blood, 1 June 2007, Vol. 109, No. 11, pp. 4635-4640.
Prepublished online as a Blood First Edition Paper on February 27, 2007; DOI 10.1182/blood-2006-10-050054.
 Previous Article | Table of Contents | Next Article 
CLINICAL TRIALS AND OBSERVATIONS
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
Jelena V. Jovanovic1,
Joannah Score2,
Katherine Waghorn2,
Daniela Cilloni3,
Enrico Gottardi3,
Georgia Metzgeroth4,
Philipp Erben4,
Helena Popp4,
Christoph Walz4,
Andreas Hochhaus4,
Catherine Roche-Lestienne5,
Claude Preudhomme5,
Ellen Solomon1,
Jane Apperley6,
Michela Rondoni7,
Emanuela Ottaviani7,
Giovanni Martinelli7,
Finella Brito-Babapulle8,
Giuseppe Saglio3,
Rüdiger Hehlmann4,
Nicholas C. P. Cross2,
Andreas Reiter4,
David Grimwade, on behalf of the European LeukemiaNet1
1 Department of Medical & Molecular Genetics, King's College London, United Kingdom;
2 Wessex Regional Genetics Laboratory, University of Southampton School of Medicine, Salisbury, United Kingdom;
3 Department of Clinical & Biological Sciences, University of Turin, Italy;
4 III Medizinische Universitätsklinik, Medizinische Fakultät Mannheim, University of Heidelberg, Mannheim, Germany;
5 Laboratoire d'Hématologie, Hôpital Calmette, Lille, France;
6 Department of Haematology, Imperial College, London, United Kingdom;
7 Institute of Hematology and Medical Oncology, University of Bologna, Italy;
8 Department of Haematology, Ealing Hospital, London, United Kingdom
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 FIP1L1-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 103-105). 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 fusion to imatinib, as compared with BCR-ABL, and underline the importance of RQ-PCR monitoring to guide management using molecularly targeted therapies.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
D. Grimwade, J. V. Jovanovic, R. K. Hills, E. A. Nugent, Y. Patel, R. Flora, D. Diverio, K. Jones, H. Aslett, E. Batson, et al.
Prospective Minimal Residual Disease Monitoring to Predict Relapse of Acute Promyelocytic Leukemia and to Direct Pre-Emptive Arsenic Trioxide Therapy
J. Clin. Oncol.,
August 1, 2009;
27(22):
3650 - 3658.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Fukushima, I. Matsumura, S. Ezoe, M. Tokunaga, M. Yasumi, Y. Satoh, H. Shibayama, H. Tanaka, A. Iwama, and Y. Kanakura
FIP1L1-PDGFR{alpha} Imposes Eosinophil Lineage Commitment on Hematopoietic Stem/Progenitor Cells
J. Biol. Chem.,
March 20, 2009;
284(12):
7719 - 7732.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Cools
FIP1L1/PDGFR{alpha}'s Kit to stimulate mast cells
Blood,
September 15, 2008;
112(6):
2179 - 2179.
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Verstovsek, A. Tefferi, J. Cortes, S. O'Brien, G. Garcia-Manero, A. Pardanani, C. Akin, S. Faderl, T. Manshouri, D. Thomas, et al.
Phase II Study of Dasatinib in Philadelphia Chromosome-Negative Acute and Chronic Myeloid Diseases, Including Systemic Mastocytosis
Clin. Cancer Res.,
June 15, 2008;
14(12):
3906 - 3915.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Nishioka, T. Ikezoe, J. Yang, A. Miwa, T. Tasaka, Y. Kuwayama, K. Togitani, H. P. Koeffler, and A. Yokoyama
Ki11502, a novel multitargeted receptor tyrosine kinase inhibitor, induces growth arrest and apoptosis of human leukemia cells in vitro and in vivo
Blood,
May 15, 2008;
111(10):
5086 - 5092.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. C. Heinrich, H. Joensuu, G. D. Demetri, C. L. Corless, J. Apperley, J. A. Fletcher, D. Soulieres, S. Dirnhofer, A. Harlow, A. Town, et al.
Phase II, Open-Label Study Evaluating the Activity of Imatinib in Treating Life-Threatening Malignancies Known to Be Associated with Imatinib-Sensitive Tyrosine Kinases
Clin. Cancer Res.,
May 1, 2008;
14(9):
2717 - 2725.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C Williams, S Kalra, U Nath, N Bown, V Wilson, B S Wilkins, and A J Neylon
FIP1L1-PDGFRA positive chronic eosinophilic leukaemia and associated central nervous system involvement
J. Clin. Pathol.,
May 1, 2008;
61(5):
677 - 680.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. D. Klion, J. Robyn, I. Maric, W. Fu, L. Schmid, S. Lemery, P. Noel, M. A. Law, M. Hartsell, C. Talar-Williams, et al.
Relapse following discontinuation of imatinib mesylate therapy for FIP1L1/PDGFRA-positive chronic eosinophilic leukemia: implications for optimal dosing
Blood,
November 15, 2007;
110(10):
3552 - 3556.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Reiter, D. Grimwade, and N. C.P. Cross
Diagnostic and therapeutic management of eosinophilia-associated chronic myeloproliferative disorders
Haematologica,
September 1, 2007;
92(9):
1153 - 1158.
[Full Text]
[PDF]
|
|
|
|
|
