Successful Treatment with Imatinib Mesylate of a CML Patient in Megakaryoblastic Crisis with Severe Fibrosis

Abstract

The prognosis of patients with chronic myeloid leukemia in blastic crisis (CML-BC) remains extremely poor, and multiagent chemotherapy regimens commonly used to treat acute leukemia offer only short-term benefits. Therefore, the advent of the novel molecularly targeted anticancer agent imatinib mesylate is a breakthrough in CML therapy. We present a CML patient in megakaryoblastic crisis with severe myelofibrosis, who was treated with imatinib at a dosage of 400 mg/day and achieved complete remission together with a marked regression of myelofibrosis after 1 month. The effect of imatinib on the long-term prognosis remains unclear, although the agent is clearly a promising drug for treating CML-BC even in cases of myelofibrosis.

Co‐existence of Philadelphia chromosome positive acute megakaryoblastic and B‐lymphoblastic mixed blast crisis of chronic myeloid leukemia with chronic lymphocytic leukemia

“…The therapeutical approach with Imatinib, after the failure of the conventional therapy in our patient, seems to be surprisingly effective as we have obtained a complete hematological and cytogenetic response and a marked reduction of bone marrow fibrosis as also reported by other authors (7). Recently, in 75 patients with blast‐phase CML, a complete hematological response with Imatinib therapy has been reported in 23% whereas a complete cytogenetic response in only 5% (8).…”

Molecular ablation of transforming growth factor β signaling pathways by tyrosine kinase inhibition: The coming of a promising new era in the treatment of tissue fibrosis

“…1-6). Tissue fibrosis causes disruption of normal organ architecture, and ultimately leads to their dysfunction and failure.…”

“…Of particular interest in the present context are results of numerous recent studies demonstrating that the non-receptor kinase c-Abl participates in some of the TGF-β downstream signaling responsible for the development of a profibrotic phenotype response in a variety of cell types. The initial observations leading to this important discovery appeared in the hematologic literature with three reports describing simultaneously a remarkable reduction of bone marrow fibrosis in patients receiving treatment for chronic myelogenous leukemia with the c-Abl inhibitor, imatinib mesylate (14-16)`. Several subsequent studies confirmed the marked improvement in myelofibrosis following imatinib administration.…”

A novel insertion mutation of K294RGG within BCR-ABL kinase domain confers imatinib resistance: sequential analysis of the clonal evolution in a patient with chronic myeloid leukemia in blast crisis

“…Although imatinib provides high complete cytogenetic response (CCyR) and major molecular response (MMR) rates to CML patients, the accumulation of clinical information on imatinib-treated patients has identified patients with treatment failure or suboptimal response [4]. Furthermore, imatinib monotherapy and the combination of imatinib and chemotherapy have also improved the hematological response in patients with CML in BC (CML-BC), although the response is generally transient [3,5,6]. Second-generation BCR-ABL kinase inhibitors, nilotinib and dasatinib, have been approved for clinical use, but their efficacy for CML-BC is also limited [7,8].…”