No abstract

No abstract

The therapeutic landscape of chronic myeloid leukemia (CML) has profoundly changed over the past 7 years. Most patients with chronic phase (CP) now have a normal life expectancy. Another goal is achieving a stable deep molecular response (DMR) and discontinuing medication for treatment-free remission (TFR). The European LeukemiaNet convened an expert panel to critically evaluate and update the evidence to achieve these goals since its previous recommendations. First-line treatment is a tyrosine kinase inhibitor (TKI; imatinib brand or generic, dasatinib, nilotinib, and bosutinib are available firstline). Generic imatinib is the cost-effective initial treatment in CP. Various contraindications and side-effects of all TKIs should be considered. Patient risk status at diagnosis should be assessed with the new EUTOS long-term survival (ELTS)score. Monitoring of response should be done by quantitative polymerase chain reaction whenever possible. A change of treatment is recommended when intolerance cannot be ameliorated or when molecular milestones are not reached. Greater than 10% BCR-ABL1 at 3 months indicates treatment failure when confirmed. Allogeneic transplantation continues to be a therapeutic option particularly for advanced phase CML. TKI treatment should be withheld during pregnancy. Treatment discontinuation may be considered in patients with durable DMR with the goal of achieving TFR.

The introduction of imatinib mesylate (IM) has revolutionized the treatment of chronic myeloid leukemia (CML). Although experience is too limited to permit evidence-based evaluation of survival, the available data fully justify critical reassessment of CML management. The panel therefore reviewed treatment of CML since 1998. It confirmed the value of IM (400 mg/day) and of conventional allogeneic hematopoietic stem cell transplantation (alloHSCT). It recommended that the preferred initial treatment for most patients newly diagnosed in chronic phase should now be 400 mg IM daily. A dose increase of IM, alloHSCT, or investigational treatments were recommended in case of failure, and could be considered in case of suboptimal response. IntroductionAfter the initial descriptions of chronic myeloid leukemia (CML) more than 150 years ago, little meaningful progress was made in its treatment for more than a century. Radiation therapy and busulfan contributed more to improving quality of life than to prolonging survival. Survival prolongation was first achieved with hydroxyurea (HU), much more with allogeneic hematopoietic stem cell transplantation (alloHSCT) and, later, in a minority of patients, with recombinant interferon-alpha (rIFN␣). 1 Understanding the pathogenesis of the disease began with the discovery of the Philadelphia (Ph) chromosome followed by appreciation of its molecular counterpart, the BCR-ABL fusion gene. 2,3 Recognition of the tyrosine kinase (TK) activity of the Bcr-Abl proteins led to the discovery of a new series of compounds targeted against BCR-ABL-encoded proteins, which inhibited the TK activity, thus aborting the signals controlling the leukemic phenotype. 4 One of the TK inhibitors, imatinib mesylate (IM), was found to have a high and relatively specific biochemical activity and an acceptable pharmacokinetic and toxicity profile, and was thus rapidly introduced into clinical practice. [5][6][7] This resulted in a revolutionary step in the management of CML and by extension a shift in paradigm for the management of cancer in general.The most recent comprehensive analysis of CML treatment was an evidence-based guideline developed in 1998 by an expert panel convened by the American Society of Hematology (ASH) covering conventional chemotherapy, rIFN␣, and alloHSCT. 8 TK inhibitors were not considered at that time but were subsequently the subjects of editorials and preliminary reviews. 7,[9][10][11][12][13][14] Although it is premature at this time to perform an evidence-based analysis of the effects of IM, the implications and consequences of the introduction of TK inhibitors are so important that it is not too early to review the available data and to discuss how the treatment of CML could be managed and further progress could be pursued based upon expert opinion. Therefore, the European LeukemiaNet appointed a panel of experts to review the current situation. This report constitutes its opinion. For personal use only. on May 10, 2018. by guest www.bloodjournal.org From Methods Panel compos...

No abstract