Key Points The cumulative incidence of AKI diagnosis post–hematopoietic stem cell transplantation was 12.9%. Calcineurin inhibitor use was associated with the highest cumulative incidence, 21.6%, ...after hematopoietic stem cell transplantation. Patients with AKI with hypertension/hypertensive disease had a 30-day survival probability of 63.9% (hazard ratio, 4.86, 95% confidence interval, 3.58 to 6.60). Patients with AKI were 2.5 times more likely to experience composite hospitalization and/or mortality at 30 days. Of patients who developed AKI, dialysis dependence has nearly tripled since 2014. Background AKI is a common complication in pediatric patients undergoing hematopoietic stem cell transplantation (HSCT), with a reported prevalence ranging from 68% to 84%. Few multicenter pediatric studies comprehensively assess the epidemiologic associations and clinical outcomes associated with AKI development. Methods An observational, retrospective analysis was conducted using an aggregated electronic health record data platform. The study population consisted of pediatric patients (age <18 years) who underwent HSCT over a 20-year period. The study groups consisted of patients with an encounter diagnosis of AKI ( n =713) and those without AKI ( n =4455). Both groups were propensity matched for age, sex, race, prior cancer diagnosis, and other comorbidities. End points were incidence, mortality risk, clinical outcomes, and prevalence of dialysis dependence. Competing risks analysis, Cox proportional hazard analyses, Kaplan–Meier survival curves, and incidence/prevalence rates were calculated. Results After matching, 688 patients were identified. Cumulative incidence of AKI diagnosis post-HSCT was 13.7%. Hypertensive disease, calcineurin inhibitors, and vancomycin were the most prevalent risk factors for AKI, with calcineurin inhibitors showing the highest cumulative incidence (21.6%). Patients with AKI with hypertensive disease had a survival probability of 63.9% at 30 days, followed by calcineurin inhibitors (64.4%) and vancomycin (65.9%). Patients with AKI were 1.7 times more likely to experience composite hospitalization and/or mortality at 30 days. At 365 days post-HSCT, patients with AKI had higher rates of all-cause emergency department visits, intensive care unit admissions, and mechanical ventilation compared with non-AKI. Of patients who developed AKI, the prevalence of dialysis dependence has nearly tripled since 2014. Conclusions The findings highlight a strong association between specific risk factors, such as hypertension, calcineurin inhibitor use, and vancomycin use, with increased mortality and adverse clinical outcomes in patients with AKI after HSCT. These results emphasize the need for preventative actions such as 24-hour BP monitoring and discontinuation of potential nephrotoxic medications.
Vascular thromboses (VT) are life-threatening events after pediatric liver transplantation (LT). Single-center studies have identified risk factors for intra-abdominal VT, but large-scale pediatric ...studies are lacking.
This multicenter retrospective cohort study of isolated pediatric LT recipients assessed pre- and perioperative variables to determine VT risk factors and anticoagulation-associated bleeding complications.
Within seven postoperative days, 31/331 (9.37%) patients developed intra-abdominal VT. Open fascia occurred more commonly in patients with VT (51.61 vs 23.33%) and remained the only independent risk factor in multivariable analysis (OR = 2.84, p = 0.012). Patients with VT received more blood products (83.87 vs 50.00%), had significantly higher rates of graft loss (22.58 vs 1.33%), infection (50.00 vs 20.60%), and unplanned return to the operating room (70.97 vs 16.44%) compared to those without VT. The risk of bleeding was similar (p = 0.2) between patients on and off anticoagulation.
Prophylactic anticoagulation did not increase bleeding complications in this cohort. The only independent factor associated with VT was open fascia, likely a graft/recipient size mismatch surrogate, supporting the need to improve surgical techniques to prevent VT that may not be modifiable with anticoagulation.
Abstract 1595▪▪This icon denotes an abstract that is clinically relevant.
Poster Board I-621
Intensive chemotherapy has dramatically improved cure rates for children with T-cell acute lymphoblastic ...leukemia (T-ALL) and lymphoblastic lymphoma (T-LL). However, short-term and long-term toxicities have also increased while response rates to salvage therapy for relapsed patients remain dismal. Unfortunately, due to limits of technology and the paucity of clinical material available in children that often present with large mediastinal masses, biologic parameters for risk stratification of pediatric T precursor malignancies are limited relative to pre-B ALL. Thus, most T-ALL/LL patients are treated similarly on current protocols. Limited biologic features for risk stratification likely results in overtreatment of some children while precluding patients with high-risk disease from novel therapeutic approaches upfront. Since aberrant signal transduction is a key feature driving malignant cell behavior, we hypothesized that malignant T cells would possess distinct signaling networks relative to normal thymocytes and that differences in signaling profiles could be used to identify distinct subpopulations of T-ALL/LL patients at diagnosis. To test this hypothesis, we developed a phospho-flow cytometry platform to interrogate signaling networks at the single cell level in normal and malignant T precursor cells. Previous studies in mice and humans demonstrated that approximately 95% of thymocytes normally die before exiting the thymus. Since functional T cell receptor (TCR) and IL-7 signals are known to be critical for normal thymocyte survival, we reasoned that malignant T cells might retain dependence on these signaling networks. We thus optimized stimulation conditions with both sub-optimal and saturating concentrations of anti-TCR, anti-CD28 co-stimulation, IL-7, PMA, and pervanadate. Anti-sera to 15 key intracellular protein targets in these signaling networks were validated. To distinguish malignant from normal cells, cell surface staining for 8 epitopes that survive the fixation and permeabilization steps of the assay was established. Fluorescent cell bar coding was utilized for analysis of multiple samples in a single tube, enabling high-throughput screening while minimizing experimental variability and reagent use. Using this novel platform we simultaneously measured the phospho-protein response of 107 signaling nodes in the basal state and in response to stimulation in precursor T cell lines and a panel of banked patient samples. Analysis of pilot data identified the most robust and key signaling nodes for each of the major MAPK, PI3K, and JAK-STAT pathways. Given the limited number of cells in most tissue bank samples, we then focused the platform on the 30 most informative signaling nodes. Simultaneous measurement of pERK, pS6, pSTAT5, pBcl-2, Bcl-Xl, pNFkB, PTEN, intracellular Notch and PI3K levels in the basal state and with stimulation reveals T-ALL/LL patient subpopulations with distinct signaling profiles. Interestingly, a dichotomous pattern of either hypo- or hyper-responsiveness to stimulation is emerging. Measurement of patient signaling networks is also elucidating complex crosstalk between the classically separate MAPK and PI3K signaling pathways. Informed by the patient data, targeted inhibitors are being used to unveil the interdependence of these pathways in response to stimulation and their role in apoptosis. We have also extended this approach to analyze drug responses in patient samples in vitro at the single cell level. Using a Casapse 3 based flow-cytometry assay, we find distinct patterns of sensitivity to dexamethasone, methotrexate, and nelarabine in primary patient samples. The data demonstrates that flow cytometry represents a powerful approach for reliably interrogating the biologic properties of malignant T cells, reveals distinct subpopulations of T-ALL/LL patients that were previously unappreciated, may potentially discover synergistic uses of targeted inhibitors for therapy and perhaps even highlight novel drug targets. This approach warrants further study to determine whether these profiles have prognostic significance and whether in vitro drug responses could be used to predict outcome in the context of clinical trials.
No relevant conflicts of interest to declare.
Imbalances in the lung microbiome, or dysbiosis, are associated with poor lung health in children and adults, as well as a variety of diseases that include cystic fibrosis, asthma and chronic ...obstructive pulmonary disease. Pulmonary disease accounts for 16% of deaths after this procedure in kids. ...making sure the lungs are as healthy as possible before the procedure is important to ensuring success. Sign up for The Conversation’s weekly science newsletter. Matt Zinter receives funding from the National Institutes of Health (K23HL146936, K12HD000850), the American Thoracic Society, the Pediatric Blood and Marrow Transplant Consortium, and the National Marrow Donor Program Amy Strelzer Manasevit Fund.
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