Insights into the Management of Chronic Myeloid Leukemia– Challenging Issues of Health Care Systems

Background: The morbidity and prevalence by chronic myeloid leukemia (CML) increases with age, with a maximum incidence between 45 and 60 years, which indicates the predominant involvement of a workable population. Patients with the accelerated and acute phases of CML experience a marked disease burden in terms of symptoms and negative effects on quality of life, productivity, and daily living activities. The increased incidence rates in the working-age population, commonly delayed diagnosis of CML in the current epidemiological context and the significant level of disability in the advanced phases of the disease may be assumed as challenging issues of hematology and public health.

The objectives of our study were to distinguish the current epidemiological features and assess the management approaches in chronic myeloid leukemia (CML).

Material and Methods: We performed the analytical, cross-sectional, observational and case-control researches of 134 patients with CML,who were treated and followed up in the Institute of Oncology from Moldova between 2005–2022. The quantitative reverse transcription polymerase chain reaction (RT-PCR) was accomplished in order to determine the expression of the BCR-ABL p210 and p190 transcripts. Tyrosine kinase inhibitors (TKIs) were used as a front-line therapy in the newly diagnosed CML patients and in the cases of resistance to non-TKIs chemotherapy and interferon-a. Thirty-nine relevant primary references 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.
Results: The diagnosis of CML was established in chronic phase in 122 (91,04 ± 2,32%) patients, in the accelerated and acute phases – in 12 (8,96 ± 2,03%). Within the whole CML cohort structure, the age groups of 40 - 49 (28.4 ± 4.89%) and 50 - 59 (19.7 ± 4.31%) years proved to be more numerous (P<0.05), being attributed to the working- age population. The rate of Ph-chromosome-positive the bone marrow cells ranged from 20 to 100%. The study of the karyotype identified the following examples of ISCN diagnosis: 46, XX, t (9; 22) (q34; q11) [20] and 46, XY, t (9; 22) (q34; q11). In the absolute majority of cases (72.7%) the Ph chromosome was detected in over 70% of the BM cellular elements. BCR-ABL p210 transcript range was 9.5-100% IS. TKIs were provided via the Max Access Solutions progam. Under the first-line TKIs therapy, the complete molecular response was obtained in 24.3% of cases. No significant differences were registered in the rate of complete hematologic response (92.3% vs 92.8%) and complete molecular response (23.8% vs 24.7%) under the TKIs medication between the elderly patients and the whole cohort of CML patients. The overall one- and 5-year survival in elderly patients treated with TKI was 97.6 and 79%, being comparable with the respective parameters in the totality of CML patients (98.5% and 87%, correspondingly).
Conclusions: The efficient diagnosis management of patients with CML should combine the morphological, cytogenetic and molecular-genetic investigations of the peripheral blood and bone marrow regardless of the evolution phase, with FISH and RT-PCR as the decision-making options. The TKIs targeted therapy remains the first-line management approach to the newly-diagnosed and relapsed CML patients regardless of the age, gender, CML phase and blood count values.