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In the era of COVID-19, the chemotherapy of patients with hematological malignancies has become the cornerstone in hematology. Secondary immunodeficiency as a result of hemoblastosis, predisposes to a more severe course of coronavirus infection, and specific antitumor treatment only exacerbates patients immunodeficiency. Thus, there is a problem of conducting chemotherapy during the COVID-19 pandemic. At the moment, there are no unified recommendations for risk assessment and choice of treatment for patients with oncohematological diseases and concomitant coronavirus infection. In this article, we present a series of clinical cases of patients with hematological malignancies diagnosed with coronavirus infection at the onset of a hematological disease or after chemotherapy. Patients with long-term persistent coronavirus infection requiring specific anticancer treatment were allocated to a separate group. We hope that this article will help to set a vector for further research, as well as serve as a clear example of the clinical situations that a hematologist may face during the COVID-19 pandemic. Copyright © 2022 ABV-Press Publishing House. All rights reserved.
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Background: According to published data, the risk of coronavirus infection (COVID-19) in patients with malignancies is 5 times higher than in those without malignancies. Objective: To evaluate in-hospital overall survival in hematological patients with grade 4 neutropenia associated with coronavirus infection. Patients: This study was conducted from April 24, 2020 to June 17, 2021 in the Department of Hematology of Moscow City Clinical Hospital No. 52 (Russian Federation) and included 76 hematological patients with grade 4 neutropenia and coronavirus infection (aged 18-91 years): • 40 patients with acute leukemias (32 with AML, 8 with ALL): 22 men with a median age of 54 years (interquartile range (IQR) 43-60) and 18 women with a median age of 61 years (IQR 56-70) and • 36 patients with lymphoproliferative diseases (mostly with aggressive non-Hodgkin's lymphomas): 13 men with a median age of 57 years (IQR 40-68) and 23 women with a median age of 63 years (IQR 35-75). All patients were brought in by ambulance from other hospitals where they had received a course of combination chemotherapy interrupted due to coronavirus infection. Results: Most pts had moderate to severe lung disease (CT severity scores were 2, 3, and 4 in 29 (38.2%), 17 (22.5%), and 8 (10%) patients, respectively);55% of patients had high C-reactive protein and procalcitonin (above 0.5 ng/mL);lactate dehydrogenase (mean 395.7 U/L) and D-dimer (mean 2533.8) levels were significantly elevated. Patients had a higher NEWS score (mean 8) and a high Charlson comorbidity index score (mean 5). Interleukin-6 and IL-1b blockers were used as pathogenetic therapy to control hypercytokinemia. Taking into account grade 4 neutropenia, the dose of interleukin blockers was reduced. In order to prevent thromboembolic complications, low molecular weight heparins were used at therapeutic doses (with anti-Xa activity monitoring). Oxygen was administered in patients with clinical signs of respiratory failure (oxygen insufflation via nasal cannulas or mask). Patients with progressive respiratory failure were transferred to intensive care unit. In order to improve humoral immune response (due to low SARS-CoV-2 IgG antibody titers), 43.4% of patients were administered replacement therapy with pathogen-reduced fresh-frozen COVID-19 convalescent plasma. This led to a pronounced IgG increase in 7 patients only. Antifungal treatment was used in 54% of cases. Empirical antibacterial treatment for community-acquired pneumonia was administered, including inhibitor-protected aminopenicillins and respiratory fluoroquinolones (as 1st line treatment), upfront antibacterial treatment for neutropenic fever (2nd line), and targeted antibacterial treatment (3rd line). • In the acute leukemia group, 25 (63%) patients died during hospital treatment and 15 (37%) subjects survived;the median overall survival was 15 days (95% CI 15-22) (Fig. 1). • In the lymphoproliferative disease group, the numbers of deaths and survivals were 22 (61%) and 14 (39%), respectively, and the median overall survival was 25 days (95% CI 11-32) (Fig. 2). The median follow-up was 24 days. Conclusions: Coronavirus infection associated with severe neutropenia (caused by tumor progression and/or combination chemotherapy) is a significant adverse factor for overall survival in patients with hematological malignancies. [Formula presented] Disclosures: No relevant conflicts of interest to declare.
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The effects of baricitinib, a selective reversible inhibitor of Janus kinase 1 and 2, in the treatment of COVID-19 are associated with different aspects of pathogenesis - inhibition of viral endocytosis, reduction of excessive inflammatory response, and mitigation of vascular and pulmonary damage, which is a strong rationale for using baricitinib to treat patients with COVID-19. In the period from April to May 2020, City Clinical Hospital No. 52 obtained clinical experience of baricitinib clinical use in the therapy of 113 patients with COVID-19:58 (51%) women and 55 (49%) men, whose average age was 57±12.6 years old. Analysis of the results of using baricitinib showed that therapy with baricitinib against the background of standard pathogenetic therapy was found to be effective in 95 (84%) patients and ineffective in 18 (16%). Significant positive changes were shown in comparison with the baseline level of the following indicators: body temperature (from 37.2+0.8°C to 36, ±0.68°C, P=0.000), blood oxygen saturation (from 95.5±3.0% to 96.5±2.2%, P=0.011), C-reactive protein (from 46.1±48.0 mg/L to 33.5±43.7 mg/L, P=0.010), National Early Warning Score (NEWS) (from 1.7±1.3 to 1.1±1.2, p=0.001).From the safety point of view, patients showed a slight decrease in the average value of the number of neutrophils - from (3.1±1.4)xl09 to (3.0±2.0)xl09 and lymphocytes - from (1.8±0,9) x 109 to (1.7±0.9) x 109, as well as minimal multidirectional changes in the mean values of transaminase activity - alanine aminotransferase changed from 33.9±23.6 U/L to 34.9±47.5 U/L, aspartate aminotransferase - from 40.6±49.0 U/L to 38.5±25.5 U/L. In general, the results obtained within the experience of the clinical use of baricitinib in 113 Russian patients with COVID-19 are consistent with the available data from foreign clinical studies and confirm the efficacy and safety of baricitinib. © Team of Authors, 2021.
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Justification. Oncological diseases, along with diabetes, hypertension, cardiovascular and chronic obstructive pulmonary diseases, are associated with severe course and worst prognosis of the new coronavirus infection - COVID-19. Due to the limited number of the international studies and the lack of the domestic publications on the analysis of the course of COVID-19 in patients with oncohematological pathology and the patient management tactics, this work seems extremely topical. Materials and methods. 24.04.2020-31.05.2020, 110 patients with oncohematological pathology associated with new coronavirus infection were observed on the basis of the hematology service of City Clinical Hospital No 52: 59 women and 51 men, mean age 58 (18-90) years. Results. Currently, 24 (22%) patients among 110 are continuing treatment. The outcome of the disease is observed in 86 (78%) patients: 50 (58%) patients were discharged from hospital with complete or partial resolution of pneumonia, 36 (42%) of the 86 patients died. The groups did not differ in gender. The median age was higher in the group of deceased patients (66 vs. 54 years in patients who had a favorable outcome after COVID-19). The somatic status ECOG 3-4 was an independent predictive factor determining the adverse outcome of the disease. The third part of the patients from the group with a fatal cases due to a severe condition in the debut of the disease immediately were hospitalized in the intensive care unit (ICU), 2 (6%) of them had died within the first day. Disposition, according to the nosology showed a significant predominance among patients with an adverse outcome associated with acute leukemia (18% vs 39%). Patients with resistant course of hemoblastosis accounted for 50% of deceased patients. Severe form of the course of COVID-19 infection was twice as frequently (46% vs 84%) among patients with an adverse outcome of the disease, that was associated with both the initial more severe group of patients (33% were hospitalized in the ICU), and less curability of pneumonia against the background of the adverse prognostic factors: the older age group, the predominance of patients with acute leukemia and resistant course of oncohematological diseases. Specific anticancer therapy and COVID-19 therapy were comparable in both groups. Conclusions. Identification of new coronavirus infection against a backdrop of oncohematological disease is associated with a severe course of COVID-19 and high death rate - 42%. According to the preliminary obtained results, the adverse prognostic factors of COVID-19 in patients with oncohematological diseases include: elderly age, the poor somatic status (ECOG 3-4), relapse or progression of hemoblastosis and nosological affiliation to acute leukemia. © 2020 Journal of Modern Oncology. All rights reserved.