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Imatinib has dramatically altered the natural history of chronic myelogenous leukemia (CML), with the majority of patients now experiencing long-term remission and improved survival. However, in addition to the well-described phenomenon of resistance to imatinib, typically due to point mutations, uncommon consequences (eg, the development of Philadelphia chromosome–negative clones) may infrequently occur. We report 2 cases of sudden BCR/ABL1+ blast crisis in patients with CML who had achieved complete hematologic remission with imatinib therapy but were obligated to discontinue therapy owing to pancytopenia. These sudden blast crises were unusual at 3 levels: first, they were of precursor T lymphoblastic lineage; second, they had a primary extranodal presentation without overt bone marrow involvement; and third, they developed after recent cessation of imatinib. These observations suggest that the occurrence of 2 such rare cases in a single institution within a 1-year time frame may reflect another unusual consequence of imatinib therapy.