1.
Risk factors for a severe disease course in children with SARS-COV-2 infection following hematopoietic cell transplantation in the pre-Omicron period: a prospective multinational Infectious Disease Working Party from the European Society for Blood and Marrow Transplantation group (EBMT) and the Spanish Group of Hematopoietic Stem Cell Transplantation (GETH) study
Averbuch, D., de la Camara, R., Tridello, G., Knelange, N. S., Bykova, T. A., Ifversen, M., Dobsinska, V., Ayas, M., Hamidieh, A. A., Pichler, H., et al
Bone marrow transplantation. 2023;:1-9
Abstract
Risk factors for severe SARS-Cov-2 infection course are poorly described in children following hematopoietic cell transplantation (HCT). In this international study, we analyzed factors associated with a severe course (intensive care unit (ICU) admission and/or mortality) in post-HCT children. Eighty-nine children (58% male; median age 9 years (min-max 1-18)) who received an allogeneic (85; 96%) or an autologous (4; 4%) HCT were reported from 28 centers (18 countries). Median time from HCT to SARS-Cov-2 infection was 7 months (min-max 0-181). The most common clinical manifestations included fever (37; 42%) and cough (26; 29%); 37 (42%) were asymptomatic. Nine (10%) children following allo-HCT required ICU care. Seven children (8%) following allo-HCT, died at a median of 22 days after SARS-Cov-2 diagnosis. In a univariate analysis, the probability of a severe disease course was higher in allo-HCT children with chronic GVHD, non-malignant disease, immune suppressive treatment (specifically, mycophenolate), moderate immunodeficiency score, low Lansky score, fever, cough, coinfection, pulmonary radiological findings, and high C-reactive protein. In conclusion, SARS-Cov-2 infection in children following HCT was frequently asymptomatic. Despite this, 10% needed ICU admission and 8% died in our cohort. Certain HCT, underlying disease, and SARS-Cov-2 related factors were associated with a severe disease course.
2.
Incidence of Adenovirus Infection in Hematopoietic Stem Cell Transplant Recipients: Findings from the AdVance Study
Sedlacek, P., Petterson, T., Robin, M., Sivaprakasam, P., Vainorius, E., Brundage, T., Chandak, A., Mozaffari, E., Nichols, G., Voigt, S.
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2018
Abstract
Adenovirus (AdV) is an increasingly recognized threat to allogeneic hematopoietic stem cell transplant (allo-HCT) recipients, particularly when infection is prolonged and unresolved. AdVance is the first multinational, multicenter study to evaluate the incidence of AdV infection in both pediatric and adult allo-HCT recipients across European transplant centers. Medical records for patients undergoing first allo-HCT between January 2013 and September 2015 were reviewed at 50 participating centers. The cumulative incidence of AdV infection (in any sample using any assay) during the 6 months following allo-HCT was 32% (95% confidence interval [CI], 30.9 to 33.4) among pediatric allo-HCT recipients (n=1736) and 6% (95% CI, 4.7 to 6.4) among adult allo-HCT recipients (n=2540). The incidence of AdV viremia ≥1000 copies/mL (a common threshold for initiation of pre-emptive treatment) was 14% (95% CI, 13.0 to 14.8) in pediatric, and 1.5% (95% CI, 1.1 to 2.0) in adult transplant recipients. Baseline risk factors for developing AdV viremia ≥1000 copies/mL included younger age, use of T-cell depletion, and donor type other than matched-related. Baseline demographic factors were broadly comparable across patients of all ages and identified by multivariate analyses. Notably, the incidence of AdV infection reduced stepwise with increasing age; younger adults (18-34 years) had a similar incidence as older pediatric patients (<18 years). This study provides a contemporary multicenter understanding of the incidence and risk factors for AdV infection following allo-HCT. These findings may help optimize infection screening and intervention criteria, particularly for younger at-risk adults.
3.
Appearance of cytomegalovirus-specific T-cells predicts fast resolution of viremia post hematopoietic stem cell transplantation
Pelak, O., Stuchly, J., Krol, L., Hubacek, P., Keslova, P., Sedlacek, P., Formankova, R., Stary, J., Hrusak, O., Kalina, T.
Cytometry Part B, Clinical Cytometry. 2017;92(5):380-388
Abstract
BACKGROUND Cytomegalovirus (CMV) specific T-cells are known to provide long-term control of CMV reactivation, which is a frequent complication of hematopoietic stem cell transplantation. We have studied 58 pediatric patients after hematopoietic stem cell transplantation who suffered from CMV reactivation to reveal which functional T cell subset is best correlating with successful reactivation resolution and which protects from reactivation episode. METHODS Detection of 30 combinatorial subsets of four types of response to ex vivo CMV stimulation (IFNgamma secretion, IL-2 secretion, CD40L upregulation and degranulation) that were detectable on either CD8+ or CD4+ T cells through flow cytometry intracellular cytokine staining was used. RESULTS We found that the presence of CD8+ dual positive (IFNgamma+ and IL-2+) cells is the most accurate functional parameter that can predict fast resolution of CMV reactivation. Next, we show that the presence of CD8+ dual positive (IFNgamma+ and IL-2+) and CD8+ IFNgamma+ cells provides a protective effect (a hazard risk of 0.28 (confidence interval 0.18 - 0.43) and 0.45 (CI 0.27 - 0.75), respectively) and the presence of corticotherapy increases the risk of reactivation (HR 2.47 (CI 1.82-3.36)). Thus, a patient without corticotherapy and with both of the critical T cell subsets present has a cumulative 19.6 times lower risk of developing CMV reactivation than a patient on corticotherapy and without CD8+ dual positive (IFNgamma+ and IL-2+) or CD8+ IFNgamma+ cells. CONCLUSIONS We have established parameters of CMV specific functional response ex vivo that can be used in assisting clinical management of patients with CMV reactivation. © 2015 International Clinical Cytometry Society.