CML Chapter

Abstract

The discovery of the tyrosine kinase inhibitor (TKI) imatinib in the early 2000's revolutionized the treatment and prognosis of patients with chronic myeloid leukemia (CML) [Hochhaus et al. in N Engl J Med 376:917-927, 2017]. The treatment of patients with CML has changed dramatically since the approval of imatinib and other TKIs. Before the TKI era, newly diagnosed patients would undergo HLA typing to try to identify a well-matched donor, and then proceed quickly to allogeneic hematopoietic cell transplantation (HCT). With the introduction of imatinib followed a few years later by dasatinib, nilotinib, then bosutinib, treatment approaches changed in a dramatic way. Transplantation is no longer an upfront treatment option for newly diagnosed CML patients, and in fact, it is very rarely used in the management of a patient with CML currently. The management of CML patients has been a model of personalized medicine or targeted therapy that is being emulated in the treatment of many other hematologic malignancies and solid tumors such as lung cancer [Soverini et al. in Mol Cancer 17:49, 2018]. The Philadelphia Chromosome (Ph) which leads to the formation of the BCR-ABL fusion gene and its product the BCR-ABL protein is the cause of CML. With effective targeting of this protein with the available TKIs, the disease is completely controllable if not curable for most patients. Life expectancy for patients with CML is essentially normal. Quality of life becomes an important goal including the potential for pregnancy, and ultimately the chance to discontinue all TKI therapy permanently. The three cases outlined below serve to highlight some of the important issues in the management of patients with CML in the post-TKI era.

Keywords: Chronic myelogenous leukemia; Drug discontinuation; Major molecular response; NCCN guidelines; Sokal score; Tyrosine kinase inhibitors.