PB2272: THERAPY AND HOSPITAL MORTALITY PREDICTORS IN HEMATOLOGICAL PATIENTS WITH 4 GRADE NEUTROPENIA AND CONCOMITANT CORONAVIRUS INFECTION

Abstract

Background: According to published data, cancer patients are 5 times more likely to contract coronavirus infection (COVID-19) than non-cancer patients. Aims: To assess and identify predictors of hospital mortality in hematological patients with grade 4 neutropenia and concomitant coronavirus infection. Methods: A prospective study included 130 patients (55% women, 45% men) aged 18 to 91 years (median 59) with acute leukemia (AL) and lymphoproliferative diseases (LPD) who had grade 4 neutropenia and coronavirus infection (COVID-19) and were observed from April 2020 to December 2021 at Moscow City Clinical Hospital 52 (Russia). The study also included a reference group of 130 patients matched by sex, age and diagnosis, with AL/LPD and COVID-19, but without grade 4 neutropenia. The statistical analysis was an intention to treat analysis with adjustment for false discovery rate. Results: AML prevailed in the AL group (80.6%), aggressive non-Hodgkin’s lymphomas in the LPD group. Distribution by disease status: 62 patients (47.7%) on chemotherapy (CT), 19 (14.6%) in remission, 23 (17.8%) with disease progression, 19 (14.6%) with newly diagnosed disease, 7 (5.3%) with a relapse. The patients had a high NEWS score (7.5) and a high Charlson comorbidity index (5). The majority had moderate or severe lung tissue damage (CT2 in 44 (33%), CT3 in 25 (20%), CT4 in 13 (10%)). There were increases in the levels of C-reactive protein (> 100 g/L in 55% of patients, mean 241.5 g/L), LDH (506 U/L), D-dimer (1866), procalcitonin (> 0.5 ng/mL in 73%). IL-6 and IL-1b blockers were used for hypercytokinemia; the dose of IL blockers was reduced in view of grade 4 neutropenia. Empiric antibiotic therapy for complications was used in 91.5% of patients. Antifungal therapy was carried out in 65% of cases. Sepsis developed in 63 (48.5%) patients. The median duration of hospitalization in patients with grade 4 neutropenia was 18 days. Transfer to the ICU was required in 78 (60%) patients in the total group and in 41 patients (52.5%) among those older than 60 years. Mortality in ICU patients: 80.7%, mortality in patients older than 60 years: 92.7%. In non-ICU patients with AL and LPD younger than 60 years, the mortality rate was 0%. Mechanical ventilation was used in 48.5% of cases. Mortality was lower in vaccinated patients than in unvaccinated ones (40% vs 51%). The mortality rates in the main group (AL 48.6%, LPD 51.7%, Fig. 1) and the reference group (AL 37.5%, LPD 13.8%, Fig. 2) showed that the presence of grade 4 neutropenia increased the risk of death almost twofold: the relative risk was 1.9 (95% CI 1.3–2.6), p=0.0001. According to the results of multivariate analysis (logistic regression), the predictors of hospital mortality in the main group were ICU stay (odds ratio 12.1 (1.4–24.0), p=0.0001), sepsis (3.0 (1.1–7.7), p=0.001), and age > 65 (3.0 (0.9–7.5), p=0.001). Severe disease progression/relapse is also a predictor of mortality (close to statistical significance). Image:Summary/Conclusion: Coronavirus infection with severe neutropenia (caused by tumor progression and/or combination chemotherapy) is a significant adverse factor of hospital mortality in patients with hematological cancers. Predictors of hospital mortality are age over 60 years, sepsis, ICU stay, and the absence of remission.