Tyrosine kinase inhibitors. It’s a little more than ten years since the first TKI, imatinib, was approved for the treatment of myeloid leukemia Chemistry Chronicle, which had no previous treatment with interferon. Two years later Ter showed international randomized trial of Interferon and STI571 trial, the superiority of imatinib over IFN / cytarabine in CHIR-99021 GSK-3 inhibitor new patients diagnosed in the chronic phase, and led to its approval for the treatment of first line. Before the development of imatinib, an effective treatment for CML in a minority of patients was limited. IFN-based therapy with hydroxyurea ridiculed Ngerten survival time compared with induced reactions lasted between 10 and 30% of patients. However, this advantage was largely low-risk patients according to Sokal nkt Descr And has been at the expense of significant toxicity t.
Allogeneic h Matopoetische stem cell transplantation Ethical first chronic phase of a compatible donor bound produced five years disease-free survival PCI-24781 MEK inhibitor rate at about 50%. However, the transplant mortality T and morbidity Concerning t Chtlich and many patients were not f Rderf compatibility available, because of co-morbidities or lack a suitable donor. All that changed dramatically with the advent of imatinib Ver. We now have the luxury to ask questions, which measured ten years ago would have appeared, especially if we are sure to set imatinib in patients whose disease is not detectable by RT-PCR. The logical extension of this question is whether patients who remain negative molecular be cured in the absence of treatment for their disease, and generally how it should define healing in this context.
Imatinib has also changed the Fa Ver One, the CML method is followed. The IRIS study established a complete cytogenetic response and major molecular response, defined as a 3-log reduction of BCR-ABL transcripts from a standardized baseline, connected as an important milestone With excellent long-term results are provided and a justification for the use of surrogate endpoints in clinical trials sp ter. Despite this unprecedented success, some clouds Appeared in the sky of imatinib. Concerns arose when it became clear that a significant proportion of patients had the IRIS study for various reasons, a fact that is not directly cumulative Kaplan-Meier reaction or graphics business was Protected leave.
It followed a treated eight years ago only 55% of patients with imatinib at the forefront in the IRIS study continued to receive imatinib, may need during the rest of the treatment, mainly due to unsatisfactory therapeutic effect or discontinued, had toxicity t. Because of these concerns is the Press Presentation, the disposition of patients, seen increasingly as a point monitoring Erg Nzung necessarily overall survival and event-free survival Sch Estimates. In addition, it became clear that the results of imatinib therapy are much less favorable in the community. A report of the H Pital Hammersmith imatinib failure defined more broadly than the IRIS study, because the drug for any reason, Including, Lich toxicity t is dropped. In addition, the lack of cytogenetic response as a failure, in line with the recommendations of the European Network of leukemia Chemistry. Using these criteria, EFS at 5 years was calculated at 63% only. Even more alarming are the results of a study, Bev Lkerung in CML patients in the North West of England based, which includes all patients diagnosed wi
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