Venous thromboembolism in patients with acute myeloid leukemia: development of a predictive model.

BACKGROUND: Patients with acute myeloid leukemia (AML) are at increased risk of venous thromboembolic events (VTE). However, thromboprophylaxis is largely underused. OBJECTIVES: This study aimed to determine possible VTE development risk factors and to develop a novel predictive model. METHODS: We conducted a retrospective cohort study of adult patients with newly diagnosed AML. We used univariate and multivariable logistic regression to estimate binary outcomes and identify potential predictors. Based on our final model, a dynamic nomogram was constructed with the goal of facilitating VTE probability calculation. RESULTS: Out of 626 eligible patients with AML, 72 (11.5%) developed VTE during 6 months of follow-up. Six parameters were independent predictors: male sex (odds ratio [OR] 1.82, 95% confidence interval [CI]: 1.077-2.065), prior history of thrombotic events (OR 2.27, 95% CI: 1.4-4.96), international normalized ratio (OR 0.21, 95% CI: 0.05-0.95), Eastern Cooperative Oncology Group performance status (OR 0.71, 95% CI: 0.53-0.94), and intensive therapy (OR 2.05, 95% CI: 1.07-3.91). The C statistics for the model was 0.68. The model was adequately calibrated and internally validated. The decision-curve analysis suggested the use of thromboprophylaxis in patients with VTE risks between 8 and 20%. CONCLUSION: We developed a novel and convenient tool that may assist clinicians in identifying patients whose VTE risk is high enough to warrant thromboprophylaxis.

Incidence, risk factors, and outcome of asymptomatic central nervous system involvement in adult patients with acute myeloid leukemia.

Examination of central nervous system (CNS) involvement is not routine diagnostic practice in adult patients with acute myeloid leukemia (AML). Therefore, many asymptomatic patients with CNS involvement might go undetected. The effect of CNS involvement on the AML disease course is not well defined, with conflicting results regarding clinical outcome. This study aimed to determine the incidence of asymptomatic CNS involvement in AML estimated by multiparametric flow cytometry of cerebrospinal fluid (MFC-CSF) at diagnosis, the related potential risk factors, and prognosis. In total, 645 patients with de novo AML were screened; 183 (28.4%) of them fulfilled institutional practice for MFC-CSF analysis based on presence of CNS symptoms and/or clinical features. CNS symptoms and signs were observed in 8/183 (4.4%) patients, but most patients (175/183, 95.6%) were asymptomatic. In the asymptomatic group, 73/175 (41.7%) patients had positive or suspicious cerebrospinal fluid (CSF) findings categorized as CNS positive (CNSpos) and 102/175 (58.3%) had normal CNS findings categorized as CNS negative (CNSneg). The presence of leukemic blasts was confirmed in 81/183 (44.3%) patients; the total incidence of CNS involvement in the whole AML group was 12.6% (81/645). Compared with asymptomatic patients with CNSneg, those with CNSpos had a significantly higher frequency of lymphadenopathy, white blood cell count ≥30 × 109/L, presence of the monocytic phenotype, and a high percentage of bone marrow (BM) blasts. The multivariate logistic regression model identified monocytic phenotype (p = 0.047) and high percentage of BM blasts (p = 0.042) as predictors for CNSpos. CNSpos did not affect overall survival in patients with AML. There was a higher incidence of CNS involvement in asymptomatic adult patients with de novo AML, emphasizing possible undervalued rates of CNS disease at diagnosis. Prospective studies should determine whether diagnostic lumbar puncture for MFC-CSF analysis and CNS prophylaxis could contribute to better selection and prognosis in this patient population.

Arterial Thrombosis in Patients with Acute Myeloid Leukemia: Incidence and Risk Factors.

BACKGROUND: Patients with hematological malignancies have an increased risk of arterial thrombotic events (ATEs) after diagnosis, compared to matched controls without cancer. However, data about incidence and risk factors for ATE development in patients with acute myeloid leukemia (AML) are missing. AIM: The objectives of this study were to determine the incidence of ATE in non-promyelocytic-AML patients and to define the potential risk factors for ATE development. METHODS: We conducted a retrospective cohort study of adult patients with newly diagnosed AML. The primary outcome was the occurrence of confirmed ATE, defined as myocardial infarction, stroke or critical limb ischemia. RESULTS: Out of 626 eligible AML patients, 18 (2.9%) patients developed ATE in the median time of 3 (range: 0.23-6) months. Half of these patients died due to ATE complications. Five parameters were predictors of ATE: BMI > 30 (p = 0.000, odds ratio [OR] 20.488, 95% CI: 6.581-63.780), prior history of TE (p = 0.041, OR 4.233, 95% CI: 1.329-13.486), presence of comorbidities (p = 0.027, OR 5.318, 95% CI: 1.212-23.342), presence of cardiovascular comorbidities (p < 0.0001, OR 8.0168, 95% CI: 2.948-21.800) and cytogenetic risk score (p = 0.002, OR 2.113, 95% CI: 1.092-5.007). CONCLUSIONS: Our study showed that patients with AML are at increased risk of ATE. The risk was increased in patients with cardiovascular comorbidities, previous thrombosis, adverse cytogenetic risk as well as BMI > 30.

Application of Rotational Thromboelastometry in Patients with Acute Promyelocytic Leukemia.

INTRODUCTION: Hemorrhagic early death (HED) remains a major cause of treatment failure among patients with acute promyelocytic leukemia (APL). We aimed to investigate the prognostic potential of rotational thromboelastometry (ROTEM) for bleeding in patients with APL. MATERIALS AND METHODS: 31 newly-diagnosed APL patients (median age of 40 years; 14 female/17 male) that underwent treatment at the Clinic of Hematology UCCS from 2016-2020 with all-trans retinoic acid and anthracyclines were recruited. CBCs (complete blood count), conventional coagulation tests (CCTs), and ROTEM parameters obtained before treatment initiation were evaluated. RESULTS: All patients demonstrated at least one ROTEM parameter out of the reference range. ROTEM parameters associated with significant hemorrhage were EXTEM clotting time (CT) (P = 0.041) and INTEM amplitude 10 (A10) (P = 0.039), however, only EXTEM CT (P = 0.036) was associated with HED. Among CBCs and CCTs, only platelets were associated with significant bleeding (P = 0.015), while D-dimer was associated with both bleeding and HED (P = 0.001 and P = 0.002, respectively). CONCLUSION: Our results indicate that ROTEM parameters may reveal hypocoagulability in APL patients and have the potential to improve current hemorrhage prognostic methods. Additionally, these results suggest the combination of ROTEM and CCTs might be useful in identifying patients at risk for HED.

COVID-19-Associated Pulmonary Aspergillosis in Patients with Acute Leukemia: A Single-Center Study.

Patients with coronavirus disease 19 (COVID-19) have increased susceptibility to secondary respiratory infections including invasive pulmonary aspergillosis (IPA). COVID-19-associated pulmonary aspergillosis (CAPA) is difficult to diagnose and can be associated with increased mortality especially in severe immunodeficiency such as hematological malignancies. Our study evaluates IPA in COVID-19 patients defined as COVID-19-CAPA among patients with acute leukemia (AL). A retrospective single-center study analyzed 46 patients with COVID-19 infection and acute leukemia, admitted to the Clinic for Haematology, Clinical Center of Serbia, Belgrade between the 2 April 2020 and 15 May 2021. During hospitalization, all participants were diagnosed with probable IPA according to the previous consensus definitions. Positive serology and galactomannan (GM) detection values in bronchoalveolar lavage (BAL) and serum were used as microbiological criteria. COVID-19 associated probable IPA was found in 22% (9/41) tested patients, where serum GM and IgM anti-Aspergillus antibodies were positive in 12% (5/41) and 10% (4/41) had positive serology for aspergillosis. One patient died while eight recovered during follow-up. Our study showed that COVID-19 might be a risk factor for IPA development in patients with AL. Early diagnosis and prompt treatment are required as reported mortality rates are high.

Acute leukemia and SARS-CoV-2 infection: clinical characteristics and risk factors for mortality.

Patients with acute leukemia (AL) have a high mortality rate from coronavirus disease 2019 (COVID-19). However, studies including patients with AL and COVID-19 are few. Fifty-one patients with AL and COVID-19 were included in our study. The mortality rate was 17/51 (29.4%). In all cases, death was associated with COVID-19 pneumonia. The major driver of outcome was the disease status (worse outcome was observed in newly diagnosed (OR, 6.00; 95% CI, 1.133 - 15.188) and patients with bone marrow aplasia (OR 4.148 [95% CI 1.133 - 15.188])). Higher mortality rate was associated with lower platelet count, prolonged PT, higher ISTH DIC score, CRP and LDH. Moreover, careful risk-benefit assessment regarding the continuation of anticancer therapy is required in patients receiving nonintensive and supportive therapy. Considering the high frequency of intrahospital viral transmission (50.98%), isolation of AL patients in single rooms, and permanent symptom monitoring and testing should be prioritized.

Himalayan P wave in a patient admitted for cardiac surgery.

Giant or Himalayan P waves are tall and peaked, the most prominent in lead II, and generally indicate enlargement of the right atrium. It has been rarely seen in clinical practice. The mechanism of Himalayan P wave formation is most likely related with prolonged conduction of electrical impulses through the enlarged right atrium. We describe the case of a patient with Himalayan P wave admitted for cardiac surgery.

Surgical treatment of intramural hematoma of the ascending aorta.

INTRODUCTION: Intramural hematoma of the aorta presents potentially fatal condition developing as a result of a vasa vasorum rupture. It is a major risk factor for developing a frank aortic dissection. CASE OUTLINE: A 65-year-old woman was admitted to our clinic for the second time, after her symptoms of chest pain and vertigo (with no electrocardiographic signs of myocardial infarction) hadn't disappeared after several months of medicament treatment (indicated in the first hospitalization). Computed tomography arteriography of the aorta showed no sign of acute aortic dissection, but revealed a contrast depo in the aortic wall of 8 x 14 mm dimensions, with no extravasation of contrast. Also, massive pericardial effusion was observed (10-30 mm in thickness). Transesophageal echocardiography confirmed these findings completely. The patient underwent surgery, in which plaque exulceration was detected on the convex side of the ascending aorta, 3 cm above the aortic valve, 1 cm in diameter, with no signs of intimal tear. A resection of the ascending aorta was performed, and the aorta was reconstructed with a 30 mm Dacron tube graft. The patient was discharged on the 14th postoperative day with satisfactory results. CONCLUSION: Intramural hematoma is not a common event, but it is potentially a fatal one. Open surgery in patients with an intramural hematoma is an effective treatment strategy, although percutaneous endovascular treatment options are being described.