Clinical Prevalence of Chemotherapy-induced Peripheral Neuropathy in Onco-hematological Patients

Background Chemotherapy-Induced Peripheral Neuropathy (CIPN) is a side effect common to many drugs in cancer treatment. CIPN symptoms are mainly sensory, as paresthesia and pain, especially in body extremities. It can affect the patient's life, requiring a dose reduction or interruption of therapy, which can impact patient's survival. Method Twenty-one hematology outpatients who were treated by neurotoxic potential drugs were selected. The Douleur neuropathique 4 questionnaire was applied, a patient form was made for data collection, and the data obtained was analyzed. Results The prevalence of CIPN was 47,62%. Five patients (23,81%) did not had signs of neurotoxicity, four (19,05%) patients were classified as Grade 1, seven (33,33% ) as Grade 2, and four (19,05%) as Grade 3, and one (4,76%) patient as Grade 4. Patients who had symptoms of CIPN had already received an average of 55,42% of the scheduled treatment. Three patients (14,29%) had to reduce the dose or change the drugs, and one patient (4,76%) had to discontinue it. Conclusions This study support the hypothesis that CIPN is an important side effect in cancer treatments. Being a cause of reducing the dose or temporarily suspending it, which can affect the success of the treatment and patient’s survival.

Immune biomarkers to predict SARS-CoV-2 vaccine effectiveness in patients with hematological malignancies

There is evidence of reduced SARS-CoV-2 vaccine effectiveness in patients with hematological malignancies. We hypothesized that tumor and treatment-related immunosuppression can be depicted in peripheral blood, and that immune profiling prior to vaccination can help predict immunogenicity. We performed a comprehensive immunological characterization of 83 hematological patients before vaccination and measured IgM, IgG, and IgA antibody response to four viral antigens at day +7 after second-dose COVID-19 vaccination using multidimensional and computational flow cytometry. Health care practitioners of similar age were the control group (n = 102). Forty-four out of 59 immune cell types were significantly altered in patients; those with monoclonal gammopathies showed greater immunosuppression than patients with B-cell disorders and Hodgkin lymphoma. Immune dysregulation emerged before treatment, peaked while on-therapy, and did not return to normalcy after stopping treatment. We identified an immunotype that was significantly associated with poor antibody response and uncovered that the frequency of neutrophils, classical monocytes, CD4, and CD8 effector memory CD127low T cells, as well as naive CD21+ and IgM+D+ memory B cells, were independently associated with immunogenicity. Thus, we provide novel immune biomarkers to predict COVID-19 vaccine effectiveness in hematological patients, which are complementary to treatment-related factors and may help tailoring possible vaccine boosters.

Treatment and in-Hospital Overall Survival in Hematological Patients with Grade 4 Neutropenia and Coronavirus Infection

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. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Comparison of Characteristics and Laboratory Tests of COVID 19-Hematological Patients from France and Brazil: Identification of Prognostic Driven Profiles

Background: The COVID-19 disease has spread throughout the world in an unprecedented way. France and Brazil confirmed the first cases in the European and South American regions with high incidence rates at the peak of the first wave of contamination along the year 2020. Patients with hematological disorders, especially malignancies, may be more vulnerable to SARS-CoV-2 infection because of the underlying disease and treatment. Since COVID-19 presentation is heterogeneous, from asymptomatic up to severe life-threatening forms and the patients with malignancies and COVID-19 admitted to the hospital show a wide range of clinical manifestations and laboratory abnormalities, it is still unclear for clinicians which patients, blood tests at admission and disease factors are associated with worse outcomes. Getting further insights into patients with specific diseases is of particular interest. We aimed to identify profiles of hematologic patients hospitalized with COVID-19 that would be associated with survival, and to assess the differences between cohorts. Methods: A binational cohort including all consecutive hematological patients aged 18 years or more with moderate or severe COVID-19, requiring hospitalization until December 2020 at two tertiary centers, from Paris, France and São Paulo, Brazil, was studied. Patients with a hospital stay of less than 24 hours were excluded. All patients were followed until the end of hospitalization; then, after discharge, survival data was recovered on medical charts or outpatient consultations, if data were available. Patient profiles were based on age, comorbidities, blood tests at admission, COVID-19 symptoms, and hematological disease characteristics. A semi-supervised learning method was first used to obtain the prognostic driven profiles; then, a classifier was identified to allow the classification of patients using only admission (baseline) data. Results: A total of 263 patients (135 from Brazil and 128 from France) were enrolled. Male patients (58.2%), elderly (≥ 65 years, 46%), with high comorbidities prevalence were frequent. Non-Hodgkin Lymphoma (29.3%), multiple myeloma (19.4%) and chronic myeloid disorders (12.9%) were the most frequent underlying hematological malignancies and 13.3% of patients had benign diseases. Most of the patients (59.7%) had undergone chemotherapy in the last six months before COVID-19 admission. The clinical presentation of COVID-19 was similar in the two countries. Fever (68.4%), dyspnea (60.1%) and cough (55.9%) were the main symptoms at admission. The ICU admission (56% versus 25%) and invasive ventilation (42% versus 19%) rates were notably higher among Brazilian patients due to scarce ICU beds during the peak of transmission in France. The overall in-hospital mortality rate was 115/263 (43.7% [95%CI 37.6-49.9]) and the median follow-up after admission was 63 days (IQR 40-98). There was no evidence of survival difference between countries after adjusting on age, comorbidities, and diagnosis. Two clusters were identified, segregating young patients with few comorbidities, low CRP, D-dimers, LDH and creatinine levels, with a 30-day survival of 77.1%, versus 46.7% in remainders. The profiles (clusters) were strongly associated with survival (p<0.001), even after adjusting on age (p<0.001) (Figure 1). We identified a set of rules to classify patients into the two profiles, using only information available at hospital admission, with a high accuracy rate (97.7% on the training set and 84.9% on the validation set). The baseline predictors consecutively selected by the model were the number of comorbidities, creatinine, CRP, a continuous regimen of chemotherapy, platelets and lymphocytes counts, a symptom of ageusia, dyspnea, hematological malignancy, high blood pressure, and symptom of myalgia. Conclusions: This analysis allowed to identify two profiles of hospitalized hematological patients with COVID-19 that have a different outcome when infected with SARS-CoV-2. The results showed the importance of CRP, LHD, and creatinine in COVID-19 presentation and prognosis, whatever the geographic origin of the patients. The identification of patterns and clinical manifestations experienced by hematological patients during moderate or severe SARS-CoV-2 infection might be helpful to medical staff in the care management and in the allocation of scarce resources. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Endothelial Activation and Stress Index (EASIX) as an Early Predictor for Mortality and Overall Survival in Hematological and Non-Hematological Patients with COVID-19: Multicenter Cohort Study

COVID-19, as a disease involving the endothelium of multiple organs, is characterized by high mortality rates among hospitalized patients. Patients with hematological malignancies are particularly at risk of an unfavorable course of COVID-19. The endothelial activation and stress index (EASIX) score has been used as a simple predictor of overall survival (OS) in specific groups of hematological cancer patients. EASIX, as a biomarker of endothelial dysfunction, might play a prognostic role in patients with COVID-19. Here, we performed a comprehensive retrospective analysis of the EASIX score in 523 hospitalized COVID-19 patients with or without coexisting hematological cancer. Hematological cancer COVID-19 patients had higher EASIX scores compared to the overall population with COVID-19. In hematological patients, EASIX was a strong predictor of the occurrence of sepsis during COVID-19. Our findings demonstrated EASIX as a strong predictor of intensive care unit admission, in-hospital mortality, the occurrence of acute renal failure and the need for hemodialysis, both in hematological and non-hematological COVID-19 patients. Patients with a high EASIX score on COVID-19 diagnosis had significantly inferior OS compared to patients with low EASIX. We showed for the first time that EASIX might serve as a simple, universal prognostic tool of OS in both hematological and non-hematological COVID-19 patients.