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Imatinib mesylate in the treatment of Core Binding Factor leukemias with KIT mutations. A report of three cases.

Cairoli R, Beghini A, Morello E, Grillo G, Montillo M, Larizza L, Morra E

Division of Haematology, Niguarda Hospital, Piazza Ospedale Maggiore 3, 20162 Milan, Italy. ctm_marencairoli@ospedaleniguarda.it

Aim of this study is to investigate the capability of Imatinib to induce an anti-leukemic effect in Core Binding Factor (CBF)-leukemia patients presenting either with extracellular juxtamembrane or kinase KIT mutations. On the basis of a screening analysis for KIT mutations, two patients with a kinase mutation and one with extracellular juxtamembrane mutation, in first or subsequent leukemic relapse, received 400mg Imatinib twice daily for 30 days. After Imatinib discontinuation, bone marrow cells were re-tested to assess the KIT mutational status and the chromosomal set. In our experience, none of the treated patients had a response by standard criteria; in particular, we did not observe any activity against acute myeloid leukemia (AML) associated with KIT kinase mutations. However, in the patient with extracellular juxtamembrane mutation, Imatinib seems to have some clinical beneficial effect and, most important, is able to abrogate the leukemic subclone carrying the mutation. Whether Imatinib, in combination with other agents, may play a role in the treatment of AML with more sensitive extracellular juxtamembrane KIT mutation remains to be determined.

Published 23 February 2005 in Leuk Res, 29(4): 397-400.
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