Management Milestones in Chronic Myeloid Leukemia Associated with Covid-19

Background: The recently published studies revealed the increased morbidity by COVID-19 in patients with hematologic tumors as compared to the allegedly healthy population. The extended incidence of COVID-19 and prevalence of chronic myeloid leukemia (CML) in a workable and socially active population may be regarded to the important issues of public health and hemato-oncology.

Objectives: The aim of the study was the assessment of the epidemiological and diagnosis patterns, treatment outcomes of COVID-19 associated with CML in order to improve the management of this hematologic malignancy.

Material and Methods: An observational and prospective study was performed in a group of 20 patients with CML, who were treated and followed up in the Institute of Oncology from the Republic of Moldova between 2005-2023. COVID-19 was diagnosed between 2020 - 2023 only in these 20 cases from the whole cohort of CML patients treated with tyrosine kinase inhibitors (TKIs). The quantitative reverse transcription polymerase chain reaction (RT-PCR) was performed with the aim to determine the expression of the BCR-ABL p210 and p190 transcripts. Nucleic acid amplification testing with a RT-PCR assay was accomplished in order to detect SARS-CoV-2 RNA from the upper respiratory tract, as the preferred initial diagnostic test for COVID-19. The study evaluated the effect of Sokal score on COVID-19 morbidity in CML patients.

Results: These 20 cases comprized 13.9% of 144 patients diagnosed with CML and followed up under the treatment with TKIs. There were 12 (60.0%) males and 8 (40.0%) females, with the male:female ratio 1.5:1 (p<0.05). The patients' age at diagnosis of COVID-19 ranged between 38-74 years (average age 52.8 years). Nine (45.0%) patients were under 50 years of age, 11 (55.0%) patients were over 50 years, and 7 (35.0%) of them were over 60 years of age. According to the WHO classification of COVID-19 severity, mild forms were registered in 5 (25.0%) cases, moderate in 10 (50.0%) and severe in 5 (25.0%) cases. The ECOG score of performance status of CML patients ranged between 0-2 at the time of diagnosis of COVID-19. The ECOG score was 2 only in 2 (10.0%) patients with active chronic phase, who experienced severe COVID-19. SARS-CoV-2 affected 10 (50.0%) low-risk patients, 8 (40.0%) intermediate-risk and 2 (10.0%) high-risk patients (p>0.05). COVID-19 developed in 18 (90.0%) patients with complete hematologic response (CHR) and in 2 (10.0%) patients without stable response to treatment with TKIs. Twelve (60.0%) patients were hospitalized for treatment of COVID-19, including all 5 (25.0%) with severe and 7 (35.0%) with moderate forms. Viral pneumonia was diagnosed by radiological examinations in 9 (45.0%) patients, including 5 (100.0%) with severe and 4 (40.0%) with moderate COVID-19 (p<0.05). Non-infectious comorbidities were registered in 4 of 5 patients with severe COVID-19 form and in 2 (20.0%) patients with moderate COVID-19 form. CML progressed into the accelerated and acute phases only in 2 (10.0%) cases with the active chronic phase and severe form of COVID-19. Nevertheless, repeated SARS-CoV-2 infection occurred only in 3 (15.0%) patients with CHR and was represented by mild (2 cases) and moderate (1 case) forms.

Conclusions: SARS-CoV-2 infection involved commonly CML patients of male gender. The older CML patients proved to be more susceptible to COVID-19. Sokal score had no impact on COVID-19 incidence in CML patients. The rate of moderate COVID-19 infection was higher in CML cases than in general population.Severe SARS-CoV-2 infection emerged in CML patients with serious non-infectious comorbidities. Patients with the advanced CML phases and severe COVID-19 encountered a poor prognosis of both conditions.

Cortes:Biopath Holdings: Consultancy, Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy; Sun Pharma: Consultancy, Research Funding; Rigel: Consultancy; Syndax: Consultancy; Nerviano: Consultancy; AbbVie: Research Funding; Ascentage: Research Funding; Lilly: Consultancy; Novartis: Consultancy, Research Funding.