CLINICAL OUTCOMES IN PATIENTS WITH COVID-19 AND HEMATOLOGIC DISEASE

Background Patients with hematologic diseases are at higher risk of the SARS-CoV-2 infection and more severe clinical outcomes of the coronavirus disease. CHRONOS19 is an observational prospective cohort study with the aim to determine the short and longer-term clinical outcomes, risk factors for disease severity and mortality, and rates of postinfectious immunity in patients with malignant and non-malignant hematologic diseases and COVID-19. Patients and Methods : Overall, 666 patients were enrolled in the study, of which 626 were included in the final data analysis. The primary endpoint was 30-day all-cause mortality. Secondary endpoints included COVID-19 complications, rates of ICU admission and mechanical ventilation, outcomes of a hematologic disease in SARS-CoV-2 infected patients, overall survival, and risk factors for disease severity and mortality. Data from 15 centers were collected at 30, 90, and 180 days after COVID-19 was diagnosed and were managed using a web-based e-data capture platform. All evaluations were performed in the pre-omicron period of COVID-19 pandemic. Results Thirty-day all-cause mortality was 18.9%. The predominant cause of death (in 80% of cases) were COVID-19 complications. At 180 days, the majority (70%) of additional deaths were due to hematologic disease progression. At a median follow-up of 5.7 [0.03-19.04] months, 6-month overall survival was 72% [95% CI: 0.69-0.76]. One-third of patients had severe SARS-CoV-2 disease. The rate of ICU admission was 22% with 77% of these patients requiring mechanical ventilation, with poor survival rate. A univariate analysis revealed that older age (≥ 60 years), male sex, malignant hematologic disease, myelotoxic agranulocytosis, transfusion dependence, refractory disease or relapse, diabetes among comorbidities, any complications, especially ARDS alone or in combination with CRS, admission to an ICU, and mechanical ventilation were associated with higher risks of mortality. Treatment of the hematologic disease was changed, postponed, or canceled in 63% of patients. At a longer follow-up (90 and 180 days), the status of the hematologic disease changed in 7.5% of patients. Conclusion Patients with hematologic disease and COVID-19 have high mortality rates, predominantly due to COVID-19 complications. At a longer-term follow-up, no significant impact of COVID-19 on the course of a hematologic disease was revealed. Micro Patients with hematologic conditions are at a higher risk of mortality due to COVID-19 compared to the general population. Further research and implementation of appropriate interventions in order to prevent the spread of the SARS-CoV-2 infection in this vulnerable patient population are warranted.

Role of Genetic Thrombophilia Markers in Thrombosis Events in Elderly Patients with COVID-19.

Thrombosis is an extremely dangerous complication in elderly patients with COVID-19. Since the first months of the pandemic, anticoagulants have been mandatory in treatment protocols for patients with COVID-19, unless there are serious contraindications. We set out to discover if genetic thrombophilia factors continue to play a triggering role in the occurrence of thrombosis in patients with COVID-19 with prophylactic or therapeutic anticoagulants. We considered the following genetic markers as risk factors for thrombophilia: G1691A in the FV gene, C677T and A1298C in the MTHFR gene, G20210A and C494T in the FII gene, and (-675) 4G/5G in the PAI-I gene. In a cohort of 176 patients, we did not obtain a reliable result indicating a higher risk of thrombotic complications when taking therapeutic doses of anticoagulants in carriers of genetic markers for thrombophilia except the C494T mutation in the FII gene. However, there was still a pronounced tendency to a higher incidence of thrombosis in patients with markers of hereditary thrombophilia, such as FV G1691A and FII G20210A mutations. The presence of the C494T (Thr165Met) allele in the FII gene in this group of patients showed a statistically significant effect of the mutation on the risk of thrombotic complications despite anticoagulant therapy.

Immunophenotype of Measurable Residual Blast Cells as an Additional Prognostic Factor in Adults with B-Cell Acute Lymphoblastic Leukemia.

Measurable residual disease (MRD) is a well-known independent prognostic factor in acute leukemias, and multicolor flow cytometry (MFC) is widely used to detect MRD. MFC is able not only to enumerate MRD accurately but also to describe an antigen expression profile of residual blast cells. However, the relationship between MRD immunophenotype and patient survival probability has not yet been studied. We determined the prognostic impact of MRD immunophenotype in adults with B-cell acute lymphoblastic leukemia (B-ALL). In a multicenter study RALL-2016 (NCT03462095), 267 patients were enrolled from 2016 to 2022. MRD was assessed at the end of induction (day 70) in 94 patients with B-ALL by six- or 10-color flow cytometry in the bone marrow specimens. The 4 year relapse-free survival (RFS) was lower in MRD-positive B-ALL patients [37% vs. 78% (p < 0.0001)]. The absence of CD10, positive expression of CD38, and high expression of CD58 on MRD cells worsened the 4 year RFS [19% vs. 51% (p = 0.004), 0% vs. 51% (p < 0.0001), and 21% vs. 40% (p = 0.02), respectively]. The MRD immunophenotype is associated with RFS and could be an additional prognostic factor for B-ALL patients.