A review and an update of European leukemianet recommendations for the management of chronic myeloid leukemia

The European LeukemiaNet (ELN) is a network of excellence articulated in several working packages (WP) dedicated to research in haematologic malignancies. The ELN WP 4 that is dedicated to chronic myeloid leukaemia (CML) begun in 2004 to discuss the management of CML in the era of tyrosine kinase inhibitors (TKIs), in collaboration with several non-European experts. The discussion led to the elaboration of treatment recommendations that were published in 2006 (Baccarani et al. 2006). A second and a third revised versions were published in 2009 and 2013 (Baccarani et al. 2009a, 2013). These recommendations were received favourably by the scientific community, the health-care professionals, and the patients, have provided shared definitions and a common language, and in several countries have contributed to a rationale and successful management of the disease. A fourth version is in preparation. In this chapter, we do not provide a formal, comprehensive, and detailed review of the recommendations that can be better found in the original publications. Here, we discuss in more details some issues that are critical and have undergone changes since 2012, when the last version was submitted. The members of the ELN CML panel have not been involved in the preparation of this chapter. All the opinions and the suggestions that are included in this chapter reflect the opinions and the personal experience of the authors. It is not intended to modify the original ELN recommendations, but to contribute to an open discussion on some critical issues, particularly on the definition of the phases of CML, on the characteristics of old and new risk scores, and on the prognostic value of several biologic risk factors. We also discuss the response to treatment, with focus on molecular response, the first-line treatment with focus on the choice between imatinib and second-generation TKIs, and on the goals of treatment. The value of second- and third-line treatment is highlighted. The issues of treatment discontinuation for treatment-free remission (TFR) and of chronic treatment continuation in patients who cannot achieve TFR, and of BCR-ABL1+ stem cells, are discussed and reviewed.