Hemorrhagic cystitis (HC) has been reported with increased frequency following post-transplantation cyclophosphamide (PTCy)–based haploidentical hematopoietic cell transplantation (HCT) along with a ...strong association with BK viruria. We prospectively evaluated the incidence of BK viruria and HC in 115 patients (median age 20 years, 2–65) undergoing PTCy-based haploidentical HCT with (
n
= 71) or without (
n
= 44) CTLA4Ig. HC prophylaxis consisted of a continuous infusion of mesna 30 min prior and 48 h post-PTCy. The overall incidence of BK viruria was 65.7%. None with BK viruria < 10
4
copies/ml developed clinical symptoms (
n
= 65). The incidence of BK viruria ≥ 10
4
copies/ml was 7.1% (
n
= 8) and 75% developed HC. The incidence of HC was 5.4% at a median of 30 days. Both BK viruria ≥ 10
4
copies/ml and HC were strongly associated with acute GVHD (
p
< 0.001). A higher NRM was observed in those with BK viruria ≥ 10
4
copies/ml, related to GVHD and its complications (41.7% vs 12.6%,
p
= 0.04). The incidences of acute GVHD, vis-à-vis, overall BK viruria, BK viruria ≥ 10
4
copies/ml, and HC, tended to be lower in patients receiving CTLA4Ig. Thus, extended infusional mesna, coupled with significant reduction in alloreactivity along with possible preservation of antiviral immunity associated with the use of CTLA4Ig, was probably responsible for a much lower incidence of BK viruria and resultant HC than reported previously following PTCy-based haploidentical HCT.
Introduction: Diffuse Large B-cell Lymphoma (DLBCL) is the most common type of Non Hodgkin Lymphoma (NHL) and is categorised into the Germinal Centre B-cell (GCB) and Activated B-cell (ABC/Non GCB) ...subtypes as per the Cell Of Origin (COO) model with the help of gene expression profiling/ immunohistochemistry. The non GCB subtype has been found to associate with the Double Expressor (DE) phenotype (i.e., co-expression of BCL-2 and c-myc by IHC and this association was substantiated and proven to be statistically significant in the present study. Aim: To categorise all DLBCL cases into GCB and Non GCB and further into DE and Non-DE by using Hans and Choi IHC alogrithm. Materials and Methods: A retrospective study of 50 patients was carried out with the help of archival material filed in the Department of Anatomic Pathology at Dharamshila Narayana Superspeciality Hospital, New Delhi, India from 1st January 2019 to 30th June 2020. The study was approved by Instituitional Ethics Committee (IEC). Chi-square test and Yates correction were used for statistical analysis. Results: The study cohort was divided into two Groups- group-A with nodal presentation and group-B with extranodal presentation. By using the Hans and Choi IHC algorithms, the cases were categorised into the GCB and non GCB subtypes in both the groups. The DE phenotype was determined in each case by the co-expression of c-myc (>40%) and BCL-2 (>50%) by IHC. By using the statistical chi-square test analysis and Yates correction, the association of DE was found to be statistically significant with non GCB type lymphomas and non DE with GCB lymphomas with p-value being 0.0005 and 0.00168, respectively. Conclusion: Due to the heterogeneity inherent in DLBCL, prediction of the DE phenotype and the COO by IHC is a sensitive tool and helps in the prognostication and therapeutic triage of patients. Hence, in all the cases diagnosed as DLBCL, a detailed morphological and IHC work up is mandatory to determine prognosis and possibly tailor therapy according to COO and DE phenotype.
Gut colonisation with carbapenem-resistant enterobacteriaceae (CRE) is a risk factor for CRE bacteremia and patients with haematological malignancies (HM) are at the highest risk of mortality.
We ...conducted a prospective surveillance study of gut colonisation with CRE and its impact on the outcome of 225 consecutive patients of HM over 28 months.
The median age of the cohort was 46 years, the majority with acute leukaemia. 48 (21%) patients were colonised with CRE on admission (CAD). Another 46 patients were colonised with CRE in the hospital (CIH). The risk factors for CAD and CIH were a diagnosis of acute leukaemia and duration of hospital stay respectively. CRE accounted for 77% of infection-related mortality (IRM). The incidence of CRE bacteremia in CRE positive patients was 18% (17/94), and mortality in those with CRE bacteremia was 100%. IRM was 35.3% in CIH group compared to 10.5% in the CAD group (p=0.0001). IRM was highest in those with acute myeloid leukaemia (AML) and CIH (54.9% p=0.0001). On multivariate analysis, CIH was the most important risk factor for IRM (HR-7.2).
Our data demonstrate that a substantial proportion of patients with HM are colonised with CRE without prior hospitalisation, but those with nosocomial colonisation have the highest risk of mortality, particularly in those with AML.
The kinetics of NKG2C
adaptive natural killer (ANK) cells and NKG2A
inhibitory NK (iNK) cells with respect to the incidence of SARS-CoV-2 infection were studied for 6 months in a cohort of healthcare ...workers following the administration of the heat-killed
(Mw group) in comparison to a control group. In both groups, corona virus disease 2019 (COVID-19) correlated with lower NKG2C
ANK cells at baseline. There was a significant upregulation of NKG2C expression and IFN-γ release in the Mw group (p=0.0009), particularly in those with a lower baseline NKG2C expression, along with the downregulation of iNK cells (p<0.0001). This translated to a significant reduction in the incidence and severity of COVID-19 in the Mw group (incidence risk ratio-0.15, p=0.0004). RNA-seq analysis at 6 months showed an upregulation of the ANK pathway genes and an enhanced ANK-mediated antibody-dependent cellular cytotoxicity (ADCC) signature. Thus, Mw was observed to have a salutary impact on the ANK cell profile and a long-term upregulation of ANK-ADCC pathways, which could have provided protection against COVID-19 in a non-immune high-risk population.
Hemophagocytic syndrome (HPS) is a rare but serious complication after allogeneic transplantation which has been reported to be particularly high after unrelated cord blood transplantation. We report ...on the incidence, risk factors and outcome of HPS in 51 patients (age 2–64 years) after haploidentical peripheral blood stem cell (PBSC) transplantation with post-transplantation cyclophosphamide (PTCY). The incidence of HPS was 12.2 %, occurring at a median of 18 days. The non-relapse mortality in patients with HPS was 83.3 % compared to 11.6 % in patients without HPS. Complete donor chimerism was documented in all patients with HPS. Definite infective etiology was identified in two patients only. The others were refractory to multiple lines of treatment and 3 patients underwent a second transplant. Even though the symptoms and biochemical markers of HPS showed prompt response in 2/3 patients undergoing a second allograft, they succumbed to infections before haematological recovery. The others succumbed to multi-organ failure or infections. Age < 10 years, transplantation for non-malignant disease and high CD34 content of the graft were identified as risk factors for HPS. Considering the fact that post-transplant HPS is usually a refractory and fatal condition, we discuss further attempts at deciphering the pathogenesis, developing modalities to prevent this complication and improve the outcome.
Objective
SARS‐CoV‐2 infection results in severe lung disease in up to 50% of hospitalised patients. The aetiopathogenesis in a subset of such patients, who continue to have progressive pulmonary ...disease following virus clearance, remains unexplored.
Methods
We investigated the role of NKG2C+/NKG2A− adaptive natural killer (ANK) cells, KLRC2 genotype and cytomegalovirus (CMV) reactivation in 22 such patients.
Results
The median duration of virus positivity was 23 days, and the median duration of hospitalisation was 48 days. The overall survival at 60 days in this group was 50%. Older age and comorbidities impacted survival negatively. CMV viraemia was documented in 11 patients, with a survival of 25% vs 80% in those without viraemia with viral load correlating with mortality. Both NK and T cells were markedly depressed in all patients at day 15. However, only persistently low ANK cells at 30 days along with an inversely high NKG2C−/NKG2A+ inhibitory NK cells significantly correlated with high CMV viraemia and mortality, irrespective of KLRC2 genotype. However, day 30 ANK cells were significantly lower in the KLRC2 deletion group. The release of IFN‐γ and perforin was severely compromised in all patients at day +15, with significant improvement in the survivors at day +30, but not in those with adverse outcome.
Conclusion
Patients with progressive lung disease even after negative SARS‐CoV‐2 status, with persistently reduced and functionally compromised ANK cells, are more likely to have CMV reactivation and an adverse outcome, independent of KLRC2 genotype.
In a cohort of patients with severe COVID‐19 lung disease who continued to have severe illness even after clearance of virus, lack of recovery of NKG2C+ adaptive NK cells correlated with cytomegalovirus viral load and increased mortality.
Introduction: The Coronavirus Disease 2019 (COVID-19) is associated with damage of cells of both innate and adaptive immunity, which results in immune system’s impairment leading to secondary ...infections. Microbiological evaluation helps in diagnostic as well as antimicrobial stewardship leading to accurate treatment of COVID-19 infected patients. Aim: To evaluate superadded bacterial and fungal infections in COVID-19 infected patients and to evaluate bacterial and fungal infections in COVID-19 non infected patients admitted with Acute Respiratory Illness (ARI). Materials and Methods: This retrospective study was carried out in a tertiary care hospital in Delhi, India, over a period of eight months (May to December, 2020). Respiratory samples, received from indoor patients with history of ARI, were processed for COVID-19 (TrueNat Real Time Polymerase chain reaction) as well as for bacterial and fungal cultures following Standard Operating Procedures (SOP). Identification and susceptibility pattern was evaluated by Vitek2 compact system (bioMérieux, Inc. Durham, North Carolina/USA). Quality control strains used were American Type Culture Collection (ATCC) Staphylococcus aureus 29213, Escherichia coli 25922 and Candida parapsilosis ATCC 22019. Minimum Inhibitory Concentration (MIC) levels were standardised as per Clinical and Laboratory Standards Institute (CLSI) guideline, 2020. All statistical analysis was done by Chi-square test using Software Statistical Package for the Social Sciences (SPSS) version 22.0. Results: Total patients admitted with the history of ARI were 542; COVID-19 Positive Group (CPG) included 115 (21.22%) while COVID-19 Negative Group (CNG) included 427 (78.78%). Growth in bacterial and fungal cultures in CPG was 59.13% (68/115) while in CNG; it was 47.78% (204/427). Among the bacterial isolates, most common isolate was Klebsiella pneumoniae {CPG: 41.93% (26/62); CNG: 36.72% (76/207)}, followed by Pseudomonas aeruginosa {CPG: 33.87% (21/62); CNG: 31.88% (66/207)}. Fungal isolates in CPG was 19.48% (15/77) (p-value 0.0445). On comparing Antimicrobial Susceptibility (AST) pattern of Enterobacterales in both CPG (n=36) and CNG (n=102), no statistically significant difference was observed. Co-morbid conditions were found mostly in CNG 89% (140/158) with ARI while only 11% (18/158) was found in CPG. Conclusion: Secondary respiratory infections are quite common amongst COVID-19 positive patients. However, growth in culture, type of isolates, Antimicrobial Resistance (AMR) was almost similar with COVID-19 non infected patients admitted with ARI. Co-morbidity had the similar impact as COVID-19 infection with respect to co-infections.
Adenovirus infections occur in 5% to 21% of patients following stem cell transplantation (SCT), with an associated mortality of up to 50%. However, a lack of prospective studies has hampered further ...developments in the understanding and management of this infection in the posttransplantation setting. We prospectively studied the incidence and outcome of adenovirus infections after SCT using preemptive screening and a policy of reduction or withdrawal of immunosuppressive therapy if the virus was isolated. The incidence of adenovirus infection was 19.7% (15 of 76), and the virus was isolated exclusively in recipients of T-cell–depleted grafts. Patients receiving 50 or 100 mg alemtuzumab in vivo were at the greatest risk of adenovirus infection (45% probability) regardless of donor type, and this was related to the slower lymphocyte recovery. Six (40%) of the 15 adenovirus-infected patients developed adenovirus disease. Severe lymphocytopenia (less than 300/μL) at the time of first detection of adenovirus was a major risk factor for development of adenovirus disease (P = .001). In addition, failure to reduce immunosuppression (P = .04) and a positive result of adenovirus polymerase chain reaction (PCR) in blood at diagnosis (P = .01) were both associated with fatal adenovirus disease. On the basis of this study, we recommend active surveillance for adenovirus infection in T-cell–depleted SCT and withdrawal or reduction of immunosuppressive treatment, if possible, in patients with adenovirus infection. Preemptive antiviral therapy is warranted for patients with severe lymphocytopenia or positive blood PCR, and in those in whom immunosuppressive therapy cannot be reduced.
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