Imatinib mesylate in chronic myeloid leukemia.

Chronic myeloid leukemia has become a paradigm for the discovery of target therapeutic approaches in the field of onco-hematology. Recognition of the tyrosine kinase activity of the p210Bcr-Abl oncoprotein led to the development of compounds targeting against BCR-ABL and then controlling the leukemic proliferation. Imatinib mesylate, one of the first tyrosine kinase inhibitors developed, was found effective and safe.

Durable responses in chronic myeloid leukemia patients maintained with lower doses of imatinib mesylate after achieving molecular remission.

In the present report, we address the question if the reduction of standard dosage of imatinib mesylate (IM) in imatinib-intolerant chronic myeloid leukemia (CML) patients with undetectable residual disease may impair their outcome. Four patients are described. The median follow up from the beginning of IM therapy was 35 months (33-59).

Novel compounds with antiproliferative activity against imatinib-resistant cell lines.

Chronic myelogenous leukemia is caused by the Bcr-Abl hybrid gene that encodes the p210Bcr-Abl chimeric oncoprotein. Although it reduces the total body burden of leukemia cells, the use of imatinib mesylate as a single agent may be accompanied by the evolution of resistance due mainly to the acquisition of point mutations. Imatinib has been combined with drugs that inhibit both the active and the inactive states of the p210Bcr-Abl kinase.

The significance of minimal residual disease in stem cell grafts and the role of purging: is it better to purge in vivo or in vitro?

Contamination of autologous graft by tumor, in addition to incomplete tumor eradication, can partly explain why relapse remains the commonest cause of treatment failure after autologous stem cell transplantation (ASCT) in patients with malignant hematologic disorders. Monitoring of minimal residual disease (MRD) is now recognized as an important diagnostic tool for assessment either of the response to treatments aimed at maximal cytoreduction and the individual risk of relapse. In order to improve cure rates, many strategies to achieve in vivo or in vitro reduction, if not eradication, of residual disease have been proposed.