Browsing by Subject "Stem cell transplant"

Now showing 1 - 3 of 3
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    A Second Look: Retrospective Identification of Thrombotic Microangiopathy in Pediatric Stem Cell Transplant Patients With Veno‐Occlusive Disease
    (Wiley, 2025) Rahim, Mahvish Q.; Nichols, Cydney; Althouse, Sandra; Rahrig, April L.; Pediatrics, School of Medicine
    Background: Veno-occlusive disease (VOD) and transplant-associated thrombotic microangiopathy (TA-TMA) remain a diagnostic and therapeutic challenge for patients undergoing hematopoietic stem cell transplant (HSCT). Both VOD and TA-TMA share an underlying etiology of microvascular endothelial damage. Potential under-recognition of TA-TMA in the context of VOD leaves HSCT recipients vulnerable to additional endothelial damage, and risk of end-organ failure. Methods: A cohort of 44 pediatric HSCT recipients diagnosed with VOD between 2010and 2019 were retrospectively evaluated for the development of TA-TMA within 1 week before and 2 months after VOD diagnosis. Patients were classified into three categories: sole diagnosis of VOD (VOD), concurrent clinical diagnosis of TA-TMA during the VOD course (VOD+TA-TMA), and patients with VOD who on retrospective review satisfied criteria for diagnosis of TA-TMA (VOD+rTA-TMA). Results: A total of 42 patients were evaluated and 50% of the patients were diagnosed clinically with TA-TMA (5) or where retrospectively identified to have TA-TMA (16). There was no difference in the severity of the course of VOD between the three groups based on need for intubation, dialysis, and pediatric intensive care unit (PICU) care. Patients in the VOD only group had the highest survival at 1 year (66.7%, n = 14) compared with patients in the VOD+TA-TMA group (60%, n = 3) and VOD+rTA-TMA group (62.5%, n = 10), p = 0.9582. Conclusion: Better understanding of the association between these two endotheliopathies is essential to improve diagnosis, treatment, and prevention of potentially fatal adverse outcomes in transplant recipients.
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    Case report: Toxic epidermal necrolysis as a unique presentation of acute graft versus host disease in a pediatric patient
    (Frontiers Media, 2025-01-23) Marlowe, Elizabeth; Palmer, Rachel; Rahrig, April L.; Dinora, Devin; Harrison, Jessica; Skiles, Jodi; Rahim, Mahvish Q.; Pediatrics, School of Medicine
    Introduction: Acute graft versus host disease (aGVHD) is a common complication of stem cell transplant (SCT), with skin involvement being most common. Severe presentations of skin aGVHD involving rapid progression of rash to bullae formation and mucosal involvement are rare. There are reports of patients with skin aGVHD that present with clinical characteristics mimicking toxic epidermal necrolysis (TEN), suggesting a possible overlap between the two. Management and outcomes of pediatric patients with this overlapping, severe presentation have rarely been described. Case presentation: This report describes an 11-year-old boy with refractory T-cell acute lymphoblastic leukemia who received peripheral blood SCT from a matched unrelated donor. Day 26 post-SCT, he developed a maculopapular facial rash, which progressed to the development of vesicles coalescing into bullae involving his conjunctiva, face, oral mucosa, and genital mucosa. Initially, systemic steroid monotherapy was initiated, but with rapid rash progression and mucosal involvement, intravenous immunoglobulin (IVIg) 2 g/kg divided over 5 days was added as management for suspected TEN-like aGVHD based on clinical findings. Ruxolitinib was subsequently started as adjunctive management for aGVHD. His skin findings continued to improve with near total resolution by day 49 post-SCT. Conclusion: We report a unique case of TEN-like aGVHD with rapid progression to >30% body surface area involvement including bullae formation and detachment of epidermis. There have been few case reports of similar presentations, most with poor outcomes. We aim to supplement the literature available by reporting our successful management with steroids, IVIg, and ruxolitinib, which resulted in early resolution of symptoms in a pediatric patient.
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    Glucose intolerance as a consequence of hematopoietic stem cell dysfunction in offspring of obese mice
    (Elsevier, 2024) Denizli, Merve; Ropa, James; Beasley, Lindsay; Ghosh, Joydeep; DeVanna, Kelli; Spice, Taylor; Haneline, Laura S.; Capitano, Maegan; Kua, Kok Lim; Pediatrics, School of Medicine
    Objective: Maternal obesity is increasingly common and negatively impacts offspring health. Children of mothers with obesity are at higher risk of developing diseases linked to hematopoietic system abnormalities and metabolism such as type 2 diabetes. Interestingly, disease risks are often dependent on the offspring's sex, suggesting sex-specific reprogramming effect of maternal obesity on offspring hematopoietic stem and progenitor cell (HSPC) function. However, the impact of maternal obesity exposure on offspring HSPC function, and the capability of HSPC to regulate offspring metabolic health is largely understudied. This study aims to test the hypothesis that offspring of obese mice exhibit sex-differences in HSPC function that affect offspring's metabolic health. Methods: We first assessed bone marrow hematopoietic stem and progenitor cell phenotype using postnatal day 21 (P21) and 8-week-old C57BL/6J mice born to control and diet-induced obese dams. We also sorted HSPC (Lineage-, Sca1+, cKit + cells) from P21 mice for competitive primary and secondary transplant, as well as transcriptomic analysis. Body weight, adiposity, insulin tolerance test and glucose tolerance tests were performed in primary and secondary transplant recipient animals. Results: We discovered sex-differences in offspring HSPC function in response to maternal obesity exposure, where male offspring of obese dams (MatOb) showed decreased HSPC numbers and engraftment, while female MatOb offspring remained largely unaffected. RNA-seq revealed immune stimulatory pathways in female MatOb offspring. Finally, only recipients of male MatOb offspring HSPC exhibited glucose intolerance. Conclusions: This study demonstrated the lasting effect of maternal obesity exposure on offspring HSPC function and implicates HSPC in metabolic regulation.