Covid Antibody Titers in Cancer Patients Following Vaccination with ChAdOx1 nCOV-19 Vaccine.

Dr. Vikram GotaCovid-19 has led to significant mortality worldwide, with an increased risk in cancer patients. Vaccination provides significant protection against the infection. The study focuses on the immunogenicity and effectiveness of ChAdOx1 nCoV-19 vaccine in cancer patients within a real-world setting. Blood samples for measuring Covid antibody titers against the receptor binding domain were collected according to a convenient sparse sampling strategy in a real-world setting, with the days of the collection coinciding with their hospital appointment. The antibody titers between different groups were analyzed descriptively. A total of 56 patients were enrolled in the study. There was no apparent effect in antibody titers between patients with solid tumors and hematological malignancies (mean ± standard deviation [SD]: 36.80 ± 41.18 vs. 52.02 ± 26.27), among patients who were undergoing chemotherapy, immunotherapy, or local therapy (mean ± SD: 42.50 ± 44.46 vs. 50.06 ± 51.39 vs. 28.70 ± 25.03), and in patients with up to 90 days and more than 90 days' interval between their last treatment and date of vaccination (mean ± SD: 38.96 ± 42.66 vs. 40.51 ± 38.65). Additionally, there were only 2/56 patients with breakthrough infection, which points out the effectiveness of this vaccine in cancer patients. The ChAdOx1 nCoV-19 vaccine has activity in cancer regardless of the tumor type, type of treatment, or time from the last treatment.

'Ironing out the risk': Assessing the effect of plateletpheresis donation frequency on iron stores in South-Asian male donors.

BACKGROUND AND OBJECTIVES: Repeated blood donation is a well-known cause of iron deficiency among donors. However, present scientific literature lacks comprehensive evidence regarding the impact of regular plateletpheresis procedures on body iron reserves. In this study, we aimed to detect and correlate iron deficiency (using iron indices) with the frequency of platelet donations. Additionally, we also analysed the correlation between other iron and haematological indices with serum ferritin to determine cost-effective parameters that may serve as an initial screening approach to determine which donors should be subjected to serum ferritin testing. MATERIALS AND METHODS: A total of 180 male participants from our platelet donor registry were enrolled in this observational cross-sectional study. Enrolment questionnaires were administered to eligible donors, and biological samples were collected during plateletpheresis donation. Biological tests such as complete blood count, reticulocyte indices, iron indices, vitamin B12 and folate were performed. RESULTS: Donors with ≥12 donations per year showed the highest prevalence of low ferritin (serum ferritin: 15-30 ng/mL) and absent iron stores (serum ferritin <15 ng/mL) (41.3% and 26.7%, respectively). Ferritin showed a significant negative correlation with recent (r = -0.346) and lifetime donations (r = -0.196). The efficacy of other indices for identifying iron depletion was much better using a serum ferritin value <15 ng/mL. CONCLUSION: Regular plateletpheresis donations can lead to varying severities of non-anaemic iron deficiency. Blood centres must regularly monitor frequent plateletpheresis donors (especially donors with more than 11 donations in a calendar year) and ideally maintain their serum ferritin above 30 ng/mL.

Relevance of vitamin D in patients undergoing HLA matched allogeneic stem cell transplant for acute leukemia.

BACKGROUND: In hematopoietic stem cell transplant (HSCT), vitamin D deficiency has been variably associated with increased complications, primarily graft versus host disease (GvHD), with a potential impact on survival. Results from various studies however, have not been consistent. This analysis was conducted to study the impact of peri-transplant vitamin D levels on transplant outcomes in patients with acute leukemia (AL) who underwent HLA matched (related/unrelated) HSCT. METHODS: This was a single center retrospective study. Patients of AL including Acute Lymphoblastic Leukemia (ALL), Acute Myeloid Leukemia (AML) or Mixed Phenotypic Acute Leukemia (MPAL) who underwent fully matched or 9/10 transplants (related/unrelated) between 2008 and 2019 were included. Vitamin D deficiency was defined as serum 25-hydroxy vitamin D3 levels ≤20 ng/ml. Those with deficiency received replacement with oral vitamin D at a dose of 60,000 IU weekly for 8 weeks followed by maintenance with daily vitamin D (800 IU/day). Vitamin D levels were repeated at 4 months from start of replacement. For patients who received correction, repeat levels >20 ng/ml were considered replete. Based on vitamin D levels in the peri-transplant period (within 120 days of transplant), patients were categorised as either vitamin D replete (> 20 ng/ml) or deplete (≤ 20 ng/ml). Peri-transplant vitamin D status was correlated with transplant outcomes. RESULTS: Of the 133 patients included, 31 were deplete (median vitamin D 15.0 ng/ml) and 102 were replete (median vitamin D 34 ng/ml) at time of transplant. Both groups were matched for age, diagnosis, EBMT score and disease risk index (DRI). There were no differences in time to neutrophil or platelet engraftment, CMV reactivation, acute GvHD (aGvHD) or chronic GvHD (cGvHD) between the two groups. Relapse rate, Progression Free Survival (PFS) and Overall Survival (OS) were also comparable between the 2 groups. CONCLUSION: The incidence of vitamin D deficiency was high in our patient cohort. Patients who were vitamin D deficient at the time of transplant did not have inferior outcomes, suggesting a limited role of vitamin D in influencing transplant outcomes.

Salivary IgA as a Surrogate Biomarker for Microbial Infections in Postoperative Patients Receiving Chemo-Radio-Therapy for Head and Neck Cancer.

Objective Radiotherapy (RT) and chemotherapy (CT) are important treatment options in patients with head and neck cancers. A common complication of this is microbial colonization or infection of mucosal surfaces. These infections may commonly be due to bacteria or yeasts. Salivary proteins with their buffering activity and immunoglobulin, especially immunoglobulin A (IgA), protect oral tissue, mucosal surfaces, and teeth from various microorganisms. This study characterizes the common microorganisms encountered and evaluates the role of salivary IgA in predicting microbial infections in this group of patients with mucositis. Methods A total of 150 adult head and neck cancer patients on CTRT were evaluated at baseline and at the end of 3 and 6 weeks, respectively. Oral swabs collected from buccal mucosa were processed in the microbiology laboratory for the presence of microorganisms. Saliva was processed for IgA level estimation on Siemens Dimension Automated biochemistry analyzer. Results Pseudomonas aeruginosa and Klebsiella pneumonia e were the most common organisms found in our patients, followed by Escherichia coli and group A beta-hemolytic Streptococci . A significant increase ( p = 0.0203) in the incidence of bacterial infection was observed in post-CTRT patients (61%) compared to pre-CTRT patients (49.33%). There was significant increase in levels of salivary IgA ( p = 0.003) in patients with bacterial and fungal infection ( n = 135/267) when compared to those in samples showing no growth ( n = 66/183). Conclusion A significant increase in the incidence of bacterial infection in post-CTRT patients was observed in this study. This study also indicated that postoperative head and neck cancer patients with oral mucositis that developed an infection were associated with high salivary IgA levels, and it may serve as a surrogate biomarker of infection in these patients.

Safety, toxicity and pharmacokinetic assessment of oral Withaferin-A in mice.

Withaferin-A (WA) is the principle component of Withania somnifera (Ashwagandha). It has several biological activities including anti-cancer, anti-diabetic, neuroprotective, hepatoprotective and immune-modulatory properties. The acute and sub-acute toxicity of oral WA was investigated in mice. In the acute toxicity study, up to 2000 mg/kg of WA was well tolerated without any signs of toxicity or death. In the sub-acute toxicity study, mice were orally administered 10, 70 and 500 mg/kg of WA respectively, daily for 28 days. Upon physiological, serum chemistry, hematology and histopathogical examination, no features suggestive of drug-induced toxicity were observed at any dose levels, thereby confirming the No-Observed Adverse Effect Level (NOAEL) to be at least 500 mg/kg. Furthermore, the oral bioavailability of WA was evaluated using single intravenous and oral doses of 10 mg/kg and 70 mg/kg respectively using sparse sampling strategy. Bioanalysis was carried out using a validated LC-MS/MS method. The AUC of WA was found to be 3996.9 ± 557.6 ng/mL*h and 141.7 ± 16.8 ng/mL*h for the intravenous and oral routes of administration respectively. The oral bioavailability was determined to be 1.8%. To conclude, WA was found to be extremely safe even at high doses, with a low oral bioavailability.

Genomic Analysis of AZD1222 (ChAdOx1) Vaccine Breakthrough Infections in the City of Mumbai.

Background: This manuscript describes the genetic features of SARS-CoV-2 mutations, prevalent phylogenetic lineages, and the disease severity amongst COVID-19-vaccinated individuals in a tertiary cancer hospital during the second wave of the pandemic in Mumbai, India. Methods: This observational study included 159 COVID-19 patients during the second wave of the pandemic from 17th March to 1st June 2021 at a tertiary cancer care centre in Mumbai. The cohort comprised of healthcare workers, staff relatives, cancer patients, and patient relatives. For comparison, 700 SARS-CoV-2 genomes sequenced during the first wave (23rd April to 25th September 2020) at the same centre were also analysed. Patients were assigned to nonvaccinated (no vaccination or <14 days from the 1st dose, n = 92), dose 1(≥14 days from the 1st dose to <14 days from the 2nd dose, n = 29), and dose 2 (≥14 days from the 2nd dose, n = 38) groups. Primary measure was the prevalence of SARS-CoV-2 genomic lineages among different groups. In addition, severity of COVID-19 was assessed according to clinical and genomic variables. Results: Kappa B.1.1671.1 and delta B.1.617.2 variants contributed to an overwhelming majority of sequenced genomes (unvaccinated: 40/92, 43.5% kappa, 46/92, 50% delta; dose 1: 14/29, 48.3% kappa, 15/29, 51.7% delta; and dose 2: 23/38, 60.5% kappa, 14/38 36.8% delta). The proportion of the kappa and delta variants did not differ significantly across the unvaccinated, dose 1, and dose 2 groups (p = 0.27). There was no occurrence of severe COVID-19 in the dose 2 group (0/38, 0% vs. 14/121, 11.6%; p = 0.02). SARS-CoV-2 genomes from all three severe COVID-19 patients in the vaccinated group belonged to the delta lineage (3/28, 10.7% vs. 0/39, 0.0%, p = 0.04). Conclusions: Sequencing analysis of SARS-COV-2 genomes from Mumbai during the second wave of COVID-19 suggests the prevalence of the kappa B.1.617.1 and the delta B.1.627.2 variants among both vaccinated and unvaccinated individuals. Continued evaluation of genomic sequencing data from breakthrough COVID-19 is necessary for monitoring the properties of evolving variants of concern and formulating appropriate immune response boosting and therapeutic strategies.

Comprehensive immune cell profiling depicts an early immune response associated with severe coronavirus disease 2019 in cancer patients.

Recent studies have highlighted multiple immune perturbations related to severe acute respiratory syndrome coronavirus 2 infection-associated respiratory disease [coronavirus disease 2019 (COVID-19)]. Some of them were associated with immunopathogenesis of severe COVID-19. However, reports on immunological indicators of severe COVID-19 in the early phase of infection in patients with comorbidities such as cancer are scarce. We prospectively studied about 200 immune response parameters, including a comprehensive immune-cell profile, inflammatory cytokines and other parameters, in 95 patients with COVID-19 (37 cancer patients without active disease and intensive chemo/immunotherapy, 58 patients without cancer) and 21 healthy donors. Of 95 patients, 41 had severe disease, and the remaining 54 were categorized as having a nonsevere disease. We evaluated the association of immune response parameters with severe COVID-19. By principal component analysis, three immune signatures defining characteristic immune responses in COVID-19 patients were found. Immune cell perturbations, in particular, decreased levels of circulating dendritic cells (DCs) along with reduced levels of CD4 T-cell subsets such as regulatory T cells (Tregs ), type 1 T helper (Th1) and Th9; additionally, relative expansion of effector natural killer (NK) cells were significantly associated with severe COVID-19. Compared with patients without cancer, the levels of terminal effector CD4 T cells, Tregs , Th9, effector NK cells, B cells, intermediate-type monocytes and myeloid DCs were significantly lower in cancer patients with mild and severe COVID-19. We concluded that severely depleted circulating myeloid DCs and helper T subsets in the initial phase of infection were strongly associated with severe COVID-19 independent of age, type of comorbidity and other parameters. Thus, our study describes the early immune response associated with severe COVID-19 in cancer patients without intensive chemo/immunotherapy.

Clinical characteristics, laboratory parameters and outcomes of COVID-19 in cancer and non-cancer patients from a tertiary Cancer Centre in India.

BACKGROUND: There is paucity of data regarding clinical characteristics, laboratory parameters and outcomes of coronavirus disease (COVID-19) in cancer versus non-cancer patients, particularly from India. MATERIALS AND METHODS: This was an observational, single-centre, retrospective analysis of patients with laboratory-confirmed COVID-19 hospitalised in our institution between 22 May 2020 and 1 December 2020. We compared baseline clinical characteristics, laboratory parameters and outcomes of COVID-19 (overall mortality, time to discharge) between cancer and non-cancer patients. RESULTS: A total of 200 COVID-19 infection episodes were analysed of which 109 (54.5%) were patients with cancer and 91 (45.5%) were patients without cancer. The median age was 43 (interquartile range [IQR]:32-57), 51 (IQR: 33-62) and 38 (IQR: 31.5-49.3) years; of whole cohort, cancer and non-cancer patients, respectively. Comparison of outcomes showed that oxygen requirement (31.2% [95% CI: 22.6-40.7] vs. 17.6% [95% CI: 10.4-26.9]; p = 0.03), median time to discharge (11 days [IQR: 6.75-16] vs. 6 days [IQR: 3-9.75]; p < 0.001) and mortality (10.0% [95% CI: 5.2-17.3] vs. 1.1% [95% CI: 0.03-5.9]; p = 0.017) were significantly higher in patients with cancer. In univariable analysis, factors associated with higher mortality in the whole cohort included diagnosis of cancer (10.1% vs. 1.1%; p = 0.027; odds ratio [OR]: 7.04), age ≥60 (17.4% vs. 2.6%; p = 0.001; OR: 7.38), oxygen requirement (22% vs. 0.6%; p < 0.001; OR: 29.01), chest infiltrates (19.2% vs. 1.4%; p < 0.001; OR: 22.65), baseline absolute lymphocyte count <1 × 109 /L (10.8% vs. 1.9%; p = 0.023; OR:5.1), C-reactive protein >1 mg% (12.8% vs. 0%; p = 0.027; OR: 24.69), serum procalcitonin >0.05 ng/ml (22.65% vs. 0%; p = 0.004; OR: 4.49) and interleukin-6 >6 pg/ml (10.8% vs. 1.3%; p = 0.036; OR: 3.08). In multivariable logistic regression, factors significantly associated with mortality were oxygen requirement (p = 0.005; OR: 13.11) and high baseline procalcitonin level (p = 0.014; OR: 37.6). CONCLUSION: Cancer patients with COVID-19 have higher mortality and require longer hospital stay. High procalcitonin levels and oxygen requirement during admission are other factors that affect outcomes adversely.

Clinical course of severe COVID19 treated with tocilizumab and antivirals post-allogeneic stem cell transplant with extensive chronic GVHD.

Recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT) are an immunocompromised group who are likely to develop severe complications and mortality because of coronavirus disease 2019 (COVID-19). We report here a 61-year-old male patient of primary myelofibrosis who underwent an allo-HSCT 6 years earlier, had chronic graft-versus-host disease (cGVHD) involving the liver, lung, eyes, and skin, (with recurrent episodes of pulmonary infections) who developed severe COVID-19. The patient was treated with tocilizumab, and a combination of lopinavir/ritonavir, ribavirin, interferon-ß1b. He was discharged after 31 days with full recovery. Tocilizumab, a humanized monoclonal antibody against IL6, has been shown to benefit respiratory manifestations in severe COVID19. However, this is first report, to our knowledge, of its use and benefit in a post HSCT recipient.

Reduction in sample rejections at the preanalytical phase - Impact of training in a tertiary care oncology center.

CONTEXT: Major clinical decisions are based on the laboratory test results where preanalytical errors are an important cause of repeat collections in patients. Identification of problem areas and continuous training of phlebotomy staff are important tools in reducing these errors. AIMS: In this study, we looked at the most common causes of sample rejection in our setting and the efficacy of the corrective measures and training processes for staff in reducing preanalytical errors. SETTINGS AND DESIGNS: This prospective study was conducted at the laboratory diagnostic services of a tertiary care oncology center, with a hematopoietic stem cell transplant unit during the period of 2012-2017 in two phases. Sample rejections from various wards were analyzed for types of rejections. MATERIALS AND METHODS: In the first phase, we analyzed the problem areas (year 2012). Following a root cause analysis, current practices of training were altered. In the second phase (2013-2017), we studied the effects of these measures. STATISTICAL ANALYSIS USED: The percent variation and P value for significance in sample rejections were calculated. RESULTS: During the year 2012, 0.36% samples were rejected by laboratory. Following interventions in the period from 2013 to 2017, samples rejected dropped to 0.19% (P < 0.0001), 0.09% (P < 0.0001), 0.09% (P = 0.8387), 0.05% (P = 0.0004), and 0.05% (P = 0.329), respectively. The reduction was significant from surgical oncology ward (P = 0.0107) and intensive care unit (P = 0.0007). From 2013 to 2017, errors significantly reduced to 0.015% for hemolyzed samples (P = 0.0001), 0.005% for contaminated samples, 0.036% for clotted samples, and 0.019% for labeling errors. CONCLUSION: Intervention in the form of targeted training helps reduce errors and improves the quality of results generated and contributes to better clinical outcomes.

Bacteriological profile and antibiotic susceptibility patterns of clinical isolates in a tertiary care cancer center.

INTRODUCTION: This increased risk of bacterial infections in the cancer patient is further compounded by the rising trends of antibiotic resistance in commonly implicated organisms. In the Indian setting this is particularly true in case of Gram negative bacilli such as Escherichia coli, Klebsiella pneumoniae and Acinetobacter spp. Increasing resistance among Gram positive organisms is also a matter of concern. The aim of this study was to document the common organisms isolated from bacterial infections in cancer patients and describe their antibiotic susceptibilities. METHODS: We conducted a 6 month study of all isolates from blood, urine, skin/soft tissue and respiratory samples of patients received from medical and surgical oncology units in our hospital. All samples were processed as per standard microbiology laboratory operating procedures. Isolates were identified to species level and susceptibility tests were performed as per Clinical Laboratory Standards Institute (CLSI) guidelines -2012. RESULTS: A total of 285 specimens from medical oncology (114) and surgical oncology services (171) were cultured. Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus and Acinetobacter spp. were most commonly encountered. More than half of the Acinetobacter strains were resistant to carbapenems. Resistance in Klebsiella pneumoniae to cephalosporins, fluoroquinolones and carbapenems was >50%. Of the Staphylococcus aureus isolates 41.67% were methicillin resistant. CONCLUSION: There is, in general, a high level of antibiotic resistance among gram negative bacilli, particularly E. coli, Klebsiella pneumoniae and Acinetobacter spp. Resistance among Gram positives is not as acute, although the MRSA incidence is increasing.

Analysis of laboratory sample rejections in the pre-analytical stage at an oncology center.

BACKGROUND: Effective patient management depends on the accuracy of laboratory results. Sample collection errors constitute an important reason for repeat collections. This study was conducted at the laboratory diagnostic services of a tertiary care oncology center with a hematopoietic stem cell transplant unit to determine the common causes of sample rejections and see the effects of corrective action. METHODS: A retrospective, intervention and prospective analysis of the samples rejected from the total samples received in our laboratories, during a nine month period from January to September 2011 was undertaken. Causes of sample rejections were determined and intervention in the form of training relevant staff was instituted. RESULTS: Out of 32,548 samples received during Jan-Sep 2011, 177 samples (0.54%) were rejected. The most common reasons for rejection in hematology and biochemistry areas were clotted blood specimen (51.2%), improperly labeled specimen containers (14.46%) and hemolyzed blood samples (11.45%). For microbiology these included labeling errors, collection of specimen in wrong containers and specimen collection date and time not being entered, unacceptable specimen source and delayed transit time (18.2% each). CONCLUSIONS: Directed interventions may help reduce the incidence of sample rejections.