Invasive fungal infections are rare in pediatric and young adult autologous hematopoietic stem cell transplant patients.

BACKGROUND: Pediatric and young adult patients undergoing autologous hematopoietic stem cell transplant (auto-HSCT) face a crucial, yet understudied, risk of invasive fungal infections (IFI), especially compared to allogeneic transplants. This gap underscores the need for research in pediatric patients undergoing auto-HSCT. Our objective was to evaluate the incidence of IFI in pediatric and young adult patients during the first year after auto-HSCT. MATERIALS AND METHODS: We conducted a single-center retrospective analysis of 150 pediatric and young adult auto-HSCT patients who underwent transplant from January 2013 to January 2023. We focused on IFI incidence within the first-year post transplant, using the European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria for IFI identification. RESULTS: Among the 150 patients analyzed, with 240 unique transplant episodes, the primary indication was neuroblastoma (37.3%), and micafungin was extensively used for prophylaxis (82.7%). There was an absence of IFI from yeast and mold species, suggesting a low IFI risk in this cohort. The incidence of IFI in pediatric auto-HSCT recipients receiving micafungin primary antifungal prophylaxis is rare. CONCLUSIONS: The findings advocate for further research to refine prophylaxis guidelines and highlight the need for individualized risk assessment to optimize post-transplant care.

Incidence of Bloodstream Infections after Hematopoietic Stem Cell Transplantation for Hurler Syndrome.

Mucopolysaccharidosis type I (MPS I) is a rare genetic disorder characterized by the deficiency of the alpha-L-iduronidase enzyme necessary for the degradation of glycosaminoglycans (GAG) in the lysosome. Hurler syndrome is the most severe form of MPS I, manifesting as multiorgan dysfunction, cognitive delay, and death, usually within ten years if left untreated. Hematopoietic stem cell transplantation (HSCT) is the optimal treatment option, providing a permanent solution to enzyme deficiency and halting cognitive decline; however, the HSCT complications transplantation-associated thrombotic microangiopathy (TA-TMA) and graft-versus-host disease (GVHD) are known risk factors for bloodstream infection (BSI). BSI is a serious complication of HSCT, contributing to poor outcomes and transplantation-related morbidity. There are little data evaluating BSI after HSCT in the Hurler syndrome population. We performed a retrospective analysis of patients with Hurler syndrome who underwent HSCT at our center between 2013 and 2020 to determine the incidence of BSI within the first year post-transplantation. Patient BSI data were collected through the first year post-HSCT. Variables including patient demographics and transplantation-related characteristics were collected, including information on BSI and mortality. Twenty-five patients with a total of 28 HSCTs were included in the analysis; the majority (n = 17; 68%) were male, with a median age of 1.1 years (interquartile range, .35 to 1.44 years) at the time of transplantation. The most common graft source was cord blood (n = 15; 54%), followed by bone marrow (n = 13; 46%), with the majority from matched unrelated donors (n = 14; 52%) and mismatched unrelated donors (n = 13; 44%). Sixteen BSIs were diagnosed in 12 patients (48%). Most infections (n = 7; 43.8%) were diagnosed in the first 20 days post-transplantation, with fewer infections observed at later time points. Seven of the 9 Hurler patients diagnosed with TA-TMA (78%) also had a BSI. The incidence rate of BSIs in Hurler patients (n = 12; 48%) was higher than the rates reported in the general pediatric HSCT population at 1-year post-transplantation (15% to 35%). Given the high rate of both TA-TMA and a BSI in Hurler patients, we suspect a possible correlation between the 2. Additionally, due to the time it takes for GAG levels to normalize post-HSCT in Hurler patients, it is reasonable to suspect that the high BSI rates in these patients are linked to their Hurler diagnosis. These findings bring awareness to possible disease-related factors contributing to high BSI rates in the Hurler population post-HSCT.

A Scalable Model to Study the Effects of Blunt-Force Injury in Adult Zebrafish.

Blunt-force traumatic brain injuries (TBI) are the most common form of head trauma, which spans a range of severities and results in complex and heterogenous secondary effects. While there is no mechanism to replace or regenerate the lost neurons following a TBI in humans, zebrafish possess the ability to regenerate neurons throughout their body, including the brain. To examine the breadth of pathologies exhibited in zebrafish following a blunt-force TBI and to study the mechanisms underlying the subsequent neuronal regenerative response, we modified the commonly used rodent Marmarou weight drop for the use in adult zebrafish. Our simple blunt-force TBI model is scalable, inducing a mild, moderate, or severe TBI, and recapitulates many of the phenotypes observed following human TBI, such as contact- and post-traumatic seizures, edema, subdural and intracerebral hematomas, and cognitive impairments, each displayed in an injury severity-dependent manner. TBI sequelae, which begin to appear within minutes of the injury, subside and return to near undamaged control levels within 7 days post-injury. The regenerative process begins as early as 48 hours post-injury (hpi), with the peak cell proliferation observed by 60 hpi. Thus, our zebrafish blunt-force TBI model produces characteristic primary and secondary injury TBI pathologies similar to human TBI, which allows for investigating disease onset and progression, along with the mechanisms of neuronal regeneration that is unique to zebrafish.