Sudden blast crisis in a chronic myeloid leukemia patient during imatinib therapy.

Imatinib mesilate (IM) is the first line therapy for chronic myeloid leukemia (CML) patients in chronic phase. Although it offers a complete cytogenetic response (CCyR) in a majority of patients, there still are some rare cases in which a sudden blast crisis (SBC) evolves. The mechanism of this unexpected event is not yet completely understood. We present the case of a female patient who developed a SBC while being under IM therapy. We do not know for sure which is the role of IM in this event, but current available data suggest that this drug may have a permissive effect on the evolution of some aggressive subclones in the context of restored normal cell population. Chronic myeloid leukemia (CML) is a myeloproliferative disorder that typically has a three phase evolution: chronic phase, accelerated phase and blast crisis. For many decades, the therapy of CML could only induce normalization of peripheral blood parameters and decrease the general symptoms and the spleen size. Interferon (INF) was the first drug able to induce a cytogenetic response. Along with its use, a peculiar but rather rare event (0.4 – 2.6% incidence) was noticed: sudden blast crisis (SBC) defined as an acute transformation that occurred unexpectedly in patients being in complete hematologic remission (CHR). Early reports described it among younger patients with more favorable disease, often associated with lymphoblastic morphology and good therapy response rates [1]. The tyrosine-kinase inhibitors dramatically changed the natural course of CML, with 80-90% complete cytogenetic responses (CCyR) and 5070% major molecular responses (MMR) [2]. Even with this therapy, SBC still occurred and hence it was suitably redefined as blastic crisis onset in a patient receiving IM, after a documented CCyR, in the immediately preceding bone marrow analysis and without an intervening accelerated phase [3]. Most authors reported clonal evolution or mosaicism according to standard cytogenetics [2-5] and found no mutations in abl kinase domain, leading to the idea that the mechanism of transformation may be less dependent of abl kinase mutations than among patients with a more “gradual” treatment failure [2], and that some patients who respond well to IM may still harbor residual leukemia progenitors that are susceptible to acquisition of molecular events that underlie progression to the blast phase [6,7]. CASE REPORT