Response of ETV6-FLT3 positive myeloid/lymphoid neoplasm with eosinophilia to inhibitors of FMS-like tyrosine kinase 3

Walz, Christoph, Erben, Philipp, Ritter, Michael, Bloor, Adrian, Metzgeroth, Georgia, Telford, Nick, Haferlach, Claudia, Haferlach, Torsten, Gesk, Stefan, Score, Joannah, Hofmann, Wolf-Karsten, Hochhaus, Andreas, Cross, Nicholas C.P. and Reiter, Andreas (2011) Response of ETV6-FLT3 positive myeloid/lymphoid neoplasm with eosinophilia to inhibitors of FMS-like tyrosine kinase 3. Blood, 118 (8), 2239-2242. (doi:10.1182/blood-2011-03-343426). (PMID:21705501)

Abstract

Imatinib-resistant tyrosine kinase (TK) fusions involving FGFR1, JAK2, or FLT3 are rare but recurrent in patients with eosinophilia-associated neoplasms. We report here 2 male patients with ETV6-FLT3+ myeloid/lymphoid neoplasms with eosinophilia who were treated with the multitargeted TK inhibitors sunitinib and sorafenib. Patient 1 achieved rapid complete hematologic response and complete cytogenetic response after 3 months of taking sunitinib. A secondary blast phase caused by clonal evolution was diagnosed after 6 months. He achieved a second complete hematologic response after taking sorafenib but relapsed 2 months later. An N841K point mutation within the TK domain of FLT3, previously reported in acute myeloid leukemia and potentially conferring resistance to sorafenib, was subsequently identified. Patient 2 was heavily pretreated according to the initial diagnosis of T-lymphoblastic lymphoma and died in sunitinib-induced pancytopenia. This report highlights the importance of a careful diagnostic workup for eosinophilia-associated neoplasms to evaluate the possibility of TK inhibitor therapy.

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Contributors

Author: Nicholas C.P. Cross

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