ABSTRACT
Background: Arterial thrombotic events (ATE) are important cause of noncancer-related deaths among patients with cancer. It is estimated that the prevalence of ATE among those patients is between 2-5%. However, data regarding acute myeloid leukemia (AML) related ATE are scarce and far less available than those related to venous thrombotic events. Aims: To determine the incidence of ATE in nonM3-AML patients and to underline the potential risk factors for ATE development. Methods: The single center, retrospective, cohort study was carried out in University Clinical Center of Serbia. Adult patients, who were diagnosed with nonM3-AML between January 2009. and December 2021. were included. In all patients the occurrence of ATE (e.g. a heart attack, a stroke, critical limb ischemia) was assessed during the active treatment and the three months following the last chemotherapy session. Diagnosis of ATE was established using clinical, laboratory and radiological methods. Patients who experienced venous thromboembolism during the treatment period were excluded. Demographic data, presence of obesity, smoking status, history of thrombosis, baseline laboratory findings (complete blood count, fibrinogen, D-dimer, PT, aPTT, LDH), leukemia-related parameters (cytogenetics (including ELN risk stratification), flow cytometry), Khorana score, ECOG PS, HCT CI score, concurrent COVID-19 were collected from patients' health records. The methods of descriptive (mean ± standard deviation, median (range), frequency (%)) and analytic statistics (Student's t-test, chi-squared test) were used. Results: A total of 545 patients (293 males (53.8%)) were included in the study. Median age of the study population was 58 (range: 18-81) years. ATE was noted in 18/545 (3.3%) subjects with following distribution: ischemic stroke 12/18 (66.7%), myocardial infarction 5/18 (27.8%), and acute lower extremity arterial thrombosis 1/18 (5.5%). ATE was diagnosed most commonly during the induction (8 (44.4%) patients), reinduction (3 (16.7%) patients) and consolidation (4 (22.2%) patients) cycles. However, cases of ATE were noted at diagnosis (1 (5.6%) patient), after transplantation (1 (5.6%) patient) or at relapse (1 (5.6%) patient) as well. ATE were significantly more frequent among patients with previous history of thromboembolic events (p = 0.016). Moreover, ATE were more common in patients with adverse cytogenetic abnormalities (p < 0.001). Other examined parameters did not significantly differ between those with and without ATE. Summary/Conclusion: The incidence of arterial thrombosis in our group was 3.3% which is in accordance with the previously published studies. Since the great number of already known risk factors for the arterial thrombosis are modifiable (e.g. smoking, diet, physical activity, excessive drinking?) it is important to actively work on the reduction on those risk factors, especially if the patient has the history of previous thromboembolic event and/or suffer from high risk AML. Prophylactic therapy with antiplatelet agents is aggravated due to the lack of firmer evidences and the presence of thrombocytopenia. Therefore further studies regarding this issue are needed.
ABSTRACT
Background: During the past one year different protocols addressing the treatment of acute leukemia (AL) during the coronavirus disease 2019 (COVID-19) outbreak have emerged. However, reliable data regarding this topic are still deficient, since only case series with heterogeneous patient population with different hematologic malignancies are available. Aims: To determine clinical characteristics of COVID-19 and to assess risk factors for mortality in patients with AL. Methods: This prospective study included 51 consecutive adult patients actively treated for AL, with verified SARS-CoV-2 infection treated at two Clinical Centres in Central Serbia. The study enrolled all symptomatic and asymptomatic patients regardless of severity of the infection. Baseline data including age, sex, body mass index, comorbidities, AL type, disease status (newly diagnosed, complete remission (CR), relapsed/ refractory (RR)), treatment (intensive, low-intensity chemotherapy, supportive care), time since AL diagnosis, outcome, laboratory parameters at the onset of infection were collected. Moreover, dana regarding COVID-19 symptoms, disease severity, COVID-19-specific therapies and time to PCR negativity were collected. Methods of descriptive and analytical statistics were used. Results: Most patients (80.4%) had acute myeloid leukemia (AML). At time of COVID-19 diagnosis 35.3% of patients were newly diagnosed with AL. Concurrent diagnosis of COVID-19 and AML was made in 5.89% patients, 23.5% were RR and 41.2% were in CR. Intensive chemotherapy was administered in 80.4% of our patients. At the time of COVID-19 diagnosis 29.4% patients had bone marrow aplasia. Intrahospital transmission was probable in 50.98% patients. Five patients who were initially asymptomatic andwith negative PCR test at the time of admission developed COVID19 symptoms within the first 48 hours. The most common symptoms of COVID-19 were fever (70.4%), fatigue (66.7%) and dyspnea (39.2%). Asymptomatic, mild to moderate, severe and critical COVID-19 was registered in 9.8%, 43.1%, 37.3% and 9.8% patients, respectively. Median time to PCR negativity was 18 days (range 10-50). Mortality for the entire cohort was 17/51 (29.4%). In all cases death was associated with COVID-19 pneumonia. Among COVID-19 symptoms dyspnea (OR 12.536 (95% CI: 3.106 - 50.597)), cephalgia (OR 5.36 (95% CI: 1.200 - 26.482) and fatigue (OR 5.921(95% CI: 1.168 - 30.019) were associated with higher mortality. Patients newly diagnosed with AL (OR 6.00 (95% CI 1.133 - 15.188) and patients with bone marrow aplasia (OR 4.148 (95% CI 1.133 - 15.188) had a significantly worse outcome in comparison with patients in CR. Additionally, pneumonia severity (OR 14.963 (95% CI 3.212 - 69.700) and need for oxygen therapy (OR 6.455 (95% CI 2.56 - 20.262) were associated with higher mortality risk. Among laboratory parameters lower platelet count (OR 0.985 (95% CI 0.973 - 0.996)), prolonged prothrombin time (OR 1.554 (95% CI 1.104 - 2.186)), higher ISTH DIC score (OR 2.122 (95% CI 1.258 - 3.576), C-reactive protein (OR 1.011 (95% CI 1.004 - 1018) and LDH (OR 1.001 (95% CI 1.000 - 1.003) were predictive for death. Summary/Conclusion: Baring in mind high mortality rate, and rate of intrahospital transmission, rigorous isolation of AL patients, permanent symptoms monitoring and prompt testing should be prioritized. Careful risk-benefit assessment regarding the continuing of anticancer therapy is required in patients receiving palliative therapy and intensive induction therapy. Conversely, there is no reason to withhold therapy for the patients in CR.