Chronic Myeloid Leukemia: An Approach to Clinico- Biological Patterns, Diagnosis and Treatment Options. Current Overview

Background: CML represents a clonal tumor of the hematopoietic system, which results from the malignant transformation of the pluripotent stem cell, while maintaining the differentiation property to all cell lines. According to current specialized literature sources, CML is characterized by uncontrolled multiplication of myeloid series cells, with an increase in circulating and total granulocyte mass, constituting 15-20% of all leukemia cases in adults, the most frequently recorded being chronic myeloproliferative neoplasia.

The objectives of our study were the descriptive evaluation of the current clinico- biologic patterns and the contemporary diagnosis options in CML, the updated identification of the management approaches and treatment strategies in this chronic myeloprolifertive neoplasm.

Material and Methods: We performed the narrative review of the updated bibliographic sources under the form of a synthesis book chapter. The chapter summarized and systematized the primary studies, dedicated to the epidemiology, etiology, pathogenesis, diagnosis and treatment issues of CML. In order to obtain the scheduled objectives, the scientific medical publications were searched via GoogleSearch, PubMed, Z-library, NCIB, Medscape, Hinari database, by the keywords: “chronic myeloid leukemia”, “incidence”, “etiology”, “pathogenesis”, “diagnosis”, “treatment”, “survival”, “prognosis”. Forty-seven relevant primary sources were identified and selected, according to the significance of the impact score, with the scientific, reproducible and transparent approach to the subject under discussion, with the subsequent data extraction, evaluation and interpretation. Intending to minimize errors, a copy of the data extraction sheet was initially produced, sharing all the elements to be extracted from the primary studies.

Results: The incidence of CML varies between 0.8 - 2.0 cases per 100,000 population. The total number of patients diagnosed with CML increased annually by 2% during 2007-2016, and the total number of deaths decreased annually by 1% during the years 2008-2017. The cause of CML is not well known yet, thus inducing screening di- fficulties in this oncopathology. Irradiation (especially in high doses) is considered a favouring etiological factor). Due to the formation of the BCR-ABL1 fusion oncogene, the tyrosine kinase activity of the ABL1 portion increases, stimulating autophosphorylation and thus being a trigger factor of malignancy of the phenotype by modifying proteins, which participate in cell cycle regulation. It increases the mitogenic activity of leukemic cells, disrupts the stromal adhesion of cells and inhibits apoptosis. The current specialized literature sources and published studies, based on representative groups of cases, identified all 3 clinical-evolutionary stages of CML: chronic (early and late), acceleration and acute one. The following 4 syndromes are described in most patients: tumor intoxication, tumor proliferation (hepato- and splenomegaly), anemic and thrombotic-hemorrhagic complications. The milepost of diagnosis is leukocytosis with basophilia and shift up to the immature granulocytes, mostly metamyelocytes, myelocytes and promyelocytes, and scanty or occasional myeloblasts. The diagnosis must be proved by cytogenetics detecting chromosomal translocation t(9;22)(q3.4;q1.1), and by RT-PCR detecting BCR-ABL transcripts. Taken into account the clonal conception of pathogenesis of hematological malignancies, TKIs, chemo- and/or immunotherapy are considered as the treatment options of choice for CML, followed by the allogeneic HSCT in case these are not effective.

Conclusions: CML morbidity increases with age, showing a maximum incidence in people aged between 35 and 65 (the mean age - 53 years), which denotes the predominant involvement of a working-age population. Identification of the chimeric BCR- ABL fusion gene and the p210 transcript with tyrosine kinase activity outlines CML at the molecular level. Allogeneic HSCT, as well as TKIs may be considered as curative options for the recovery of patients with CML in the chronic phase.