Abstract
With an annual incidence of 1–2 in a million, Ph*(+) chronic myeloid leukemia (CML) is a clonal hematopoietic stem cell disease that makes myeloid neoplastic cells breed out of control. This BCR-ABL(+) myeloproliferative disease makes up about 15%–20% of all leukemia cases in adults. CML is seen more in males than females, with a rate of three to two. However, it does not show differences in prevalence in terms of age. CML consists of three clinical phases. The first one is the chronic phase, defined by rising white blood cell levels and also by myeloid proliferation and bone marrow maturation. While this phase does not exhibit complications, in diagnosis, it comprises most of the patients. The second phase is the accelerated phase, which the disease progresses to if it is not treated or does not respond to treatment. This usually takes about 3 years. The third phase is the blastic phase. The chronic phase can still progress to the next two phases within the first 2 years, with a rate of 10%. In the following years, the possibility increases by 15%–20% each year. Tyrosine kinase inhibitors (TKIs) are revolutionary drugs for the management of disease course in CML. The aim of this review is to assess current approaches to CML patients’ follow-up and treatment with TKIs. A literature search on CML and TKIs was made in PubMed, Web of Science, and Scopus with particular focus on randomized clinical trials, recommendations, guidelines, and expert opinions. In managing CML, various treatment methods have been utilized for many decades. Prior to the development of TKIs, interferon alpha was the primary tool, which was then complemented by allogeneic hematopoietic stem cell transplantation (HSCT). HSCT was successful in slowing the disease down in the long term and curing up to 50% of patients. Then the coming of the imatinib era opened up different treatment perspectives. For the patients resistant or intolerant to imatinib, second- and third-generation TKIs are successfully used in distinct CML disease states. The survival benefits of TKIs including imatinib, nilotinib, dasatinib, bosutinib, and ponatinib for CML patients are outstanding. TKI-related adverse events could impact the clinical course, especially in long-term drug administrations. The current aim for CML disease management in the TKI era is to provide age- and sex-matched normal life duration to CML patients.
Highlights
Defined by the spreading of myeloid neoplastic cells in the circulating blood and in the bone marrow, chronic myeloid leukemia (CML) is a malignant clonal hematological disease
Imatinib mesylate as frontline treatment From previous studies on the ideal dose of imatinib to be used for CML patients, the frontline treatment is recommended as imatinib mesylate at 400 mg/day
In a study that applied 800 mg/day imatinib mesylate as the frontline treatment in patients with risky Sokal scores, the rates observed at 12 months and 24 months were as follows: complete cytogenetic response (CCyR) at 88% and 91% and major molecular response (MMR) at 56% and 73%, respectively
Summary
Defined by the spreading of myeloid neoplastic cells in the circulating blood and in the bone marrow, chronic myeloid leukemia (CML) is a malignant clonal hematological disease. The definition, classification, and scoring of CML CML was defined as the discovery of t(9;22) (q34.1;q11.2) by traditional cytogenetics along with the discovery of BCR-ABL1 by molecular genetic practices by the World Health Organization in its revision of myeloid neoplasm classification in 2016 This classification included complete karyotype and bone marrow morphologic findings to verify the myeloid disease. Prior to the use of inhibitors, Sokal CML scoring was a widely used system It is based on the age, spleen, blasts, and platelets of the patient. In a study that applied 800 mg/day imatinib mesylate as the frontline treatment in patients with risky Sokal scores, the rates observed at 12 months and 24 months were as follows: CCyR at 88% and 91% and MMR at 56% and 73%, respectively. Hughes et al compared 600 mg/day imatinib mesylate with 800 mg/day and found the response rates for the 800 mg/day group at 12 months and 24 months to be as follows: CCyR at 88% and 90% and MMR at 47% and 73%, respectively [15]
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