Publications by authors named "Timothy A Driscoll"

Background: Hematopoietic cell transplantation (HCT) is the standard of care treatment for children with Hurler syndrome (HS). This study describes the impact of newborn screening (NBS) on HCT outcomes for these patients.

Methods: Retrospective study of HS patients diagnosed through NBS and referred to Duke from 2017 to 2023.

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Article Synopsis
  • Ceroid lipofuscinosis neuronal (CLN) is a rare neurodegenerative disorder that affects children, causing issues like epilepsy, vision loss, and early death.
  • A study analyzed 8 patients with different types of CLN who underwent umbilical cord blood transplant (UCBT) between 2012 and 2020, finding that all patients had successful donor cell engraftment without severe transplant-related deaths.
  • Complications like severe graft-versus-host disease and infections were noted, but overall, UCBT showed promise in stabilizing some patients' conditions, highlighting the need for more research and longer follow-up to fully understand its impact.
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  • The study investigates the use of mediports for administering CAR T cell therapy in patients with B-cell malignancies, aiming to establish standardized practices in this area due to previous concerns about effectiveness and safety.
  • Data was collected from 34 medical centers, analyzing 504 CAR T cell infusions, making it one of the largest reports on this topic since CAR T cell commercialization began in 2017.
  • Results showed that 85% of centers accepted mediports as standard practice, with no incidents of CAR T cell infiltration reported among the 184 patients infused via mediports, supporting their safe use in clinical settings.
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Chronic graft-versus-host disease (cGVHD) of the skin is a serious cause of long-term morbidity and mortality among patients who receive hematopoietic stem cell transplants. Systemic corticosteroids remain first-line treatment for cutaneous cGVHD; however, there is currently no consensus on second-line therapy for steroid-refractory disease. We herein present a case of a pediatric patient with severe cGVHD of the skin, nonresponsive to corticosteroids, who was successfully treated with a prolonged course of ruxolitinib with minimal side effects.

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Background: Tisagenlecleucel, an anti-CD19 chimeric antigen receptor T cell therapy, has demonstrated efficacy in children and young adults with relapsed/refractory B cell acute lymphoblastic leukemia (B-ALL) in two multicenter phase 2 trials (ClinicalTrials.gov, NCT02435849 (ELIANA) and NCT02228096 (ENSIGN)), leading to commercialization of tisagenlecleucel for the treatment of patients up to age 25 years with B-ALL that is refractory or in second or greater relapse.

Methods: A pooled analysis of 137 patients from these trials (ELIANA: n=79; ENSIGN: n=58) was performed to provide a comprehensive safety profile for tisagenlecleucel.

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Allogeneic hematopoietic stem cell transplantation is curative for primary immunodeficiencies. Bone marrow from an unaffected human leukocyte antigen (HLA)-identical sibling donor is the ideal graft source. For minor donors, meaningful consent or assent may not be feasible, and permission from parents or legal guardians is considered acceptable.

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Infections and graft-versus-host disease (GVHD) have historically resulted in high mortality among children undergoing umbilical cord blood transplantation (UCBT). However, recent advances in clinical practice have likely improved outcomes of these patients. We conducted a retrospective cohort study of children (<18years of age) undergoing UCBT at Duke University between January 1, 1995 and December 31, 2014.

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Purpose: At our institution, a high proportion of children with onychocryptosis (ingrown toenail) requiring surgical intervention were noted to have a history of hematopoietic stem cell transplantation (HSCT). We analyzed the characteristics of patients who underwent surgical intervention for onychocryptosis and examined our institutional HSCT database to determine if an association exists between onychocryptosis and HSCT.

Materials And Methods: Surgical cases for onychocryptosis performed from 2000 to 2012 were identified.

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Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disorder of immune dysregulation characterized by fever, hepatosplenomegaly, cytopenias, central nervous system disease, increased inflammatory markers, and hemophagocytosis. Currently, allogeneic hematopoietic stem cell transplantation is the only curative approach for patients with HLH, with reported survival ranging from 50% to 70% with myeloablative conditioning (MAC) regimens. However, donor availability and transplantation-related mortality associated with conventional MAC are major barriers to success.

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Background: The value of gross total resection (GTR) for children with high-risk neuroblastoma (NB) is controversial. We hypothesized that patients undergoing GTR would demonstrate improved overall survival (OS) compared those having
Methods: Using a single institutional database, we reviewed the medical records of all children with high-risk NB undergoing hematopoietic stem cell transplantation (HSCT) as part of multimodality therapy from 1990 to 2012.

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Reduced-intensity conditioning (RIC) regimens have the potential to decrease transplantation-related morbidity and mortality. However, engraftment failure has been prohibitively high after RIC unrelated umbilical cord blood transplantation (UCBT) in chemotherapy-naïve children with nonmalignant diseases (NMD). Twenty-two children with a median age of 2.

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The curative potential of hematopoietic stem cell transplantation in patients with chronic granulomatous disease depends on availability of a suitable donor, successful donor engraftment, and maintenance of long-term donor chimerism. Twelve consecutive children (median age, 59.5 months; range, 8-140 months) with severe chronic granulomatous disease (serious bacterial/fungal infections pretransplantation; median, 3; range, 2-9) received myeloablative hematopoietic stem cell transplantation using sibling bone marrow ([SibBM]; n = 5), unrelated cord blood (UCB; n = 6), and sibling cord blood (n = 1) at our center between 1997 and 2010.

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Voriconazole is the treatment of choice for invasive aspergillosis and its use is increasing in pediatrics. Minimal pharmacokinetic data exist in young children. We report voriconazole concentrations for 10 children <3 years of age and pharmacokinetic parameters for 1 infant who had therapeutic drug monitoring performed.

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Voriconazole pharmacokinetics are not well characterized in children despite prior studies. To assess the appropriate pediatric dosing, a study was conducted in 40 immunocompromised children aged 2 to <12 years to evaluate the pharmacokinetics and safety of voriconazole following intravenous (IV)-to-oral (PO) switch regimens based on a previous population pharmacokinetic modeling: 7 mg/kg IV every 12 h (q12h) and 200 mg PO q12h. Area under the curve over the 12-h dosing interval (AUC(0-12)) was calculated using the noncompartmental method and compared to that for adults receiving approved dosing regimens (6 → 4 mg/kg IV q12h, 200 mg PO q12h).

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The current voriconazole dosing recommendation in adolescents is based on limited efficacy and pharmacokinetic data. To confirm the appropriateness of dosing adolescents like adults, a pharmacokinetic study was conducted in 26 immunocompromised adolescents aged 12 to <17 years following intravenous (IV) voriconazole to oral switch regimens: 6 mg/kg IV every 12 h (q12h) on day 1 followed by 4 mg/kg IV q12h, then switched to 300 mg orally q12h. Area under the curve over a 12-hour dosing interval (AUC(0-12)) was calculated using a noncompartmental method and compared to the value for adults receiving the same dosing regimens.

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Unlabelled: Hypoxia is a common feature of solid tumors. Up-regulation of hypoxia-inducing factor-1 (HIF-1) occurs in the majority of primary malignant tumors and in two-thirds of metastases, while most normal tissues are negative. HIF-1 induces the glycolytic phenotype, which creates an acidic extracellular microenvironment and associated pH gradient such that drugs that are weak acids are selectively taken up and retained in acidic tumors.

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Myelodysplastic syndromes (MDS) respond poorly to chemotherapy. Between 1995 and 2006, 23 pediatric patients with MDS were transplanted with unrelated donor umbilical cord blood (UUCB) at our center. The median age was 11.

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Outcomes of 159 young patients with inherited metabolic disorders (IMDs) undergoing transplantation with partially HLA-mismatched unrelated donor umbilical cord blood were studied to investigate the impact of graft and patient characteristics on engraftment, overall survival (OS), and graft-versus-host disease (GVHD). Patients received myeloablative chemotherapy (busulfan, cyclophosphamide, ATG) and cyclosporine-based GVHD prophylaxis. Infused cell doses were high (7.

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Allogeneic hematopoietic stem cell transplantation (HSCT) is curative for chronic granulomatous disease (CGD), but many patients lack a suitably matched related donor. We report successful outcomes after mismatched, unrelated-donor umbilical cord blood transplantation (uUCBT) in two boys with X-linked CGD. Both patients experienced autologous recovery after first transplants, required second transplants to achieve durable donor engraftment, and are alive 27 and 15 months post-transplant.

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Background: Most solid human tumors exist in an acidic microenvironment, due in part to inefficient vasculature and a higher intrinsic rate of glycolysis. This leads to a tumor-selective pH gradient, which can be exploited therapeutically with antitumor agents such as the camptothecins (CPTs). Previous work in this laboratory has shown that camptothecin activity is enhanced 40- to 60-fold in monolayer cell culture by reducing the extracellular pH to 6.

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Allogeneic stem cell transplantation with umbilical cord blood (UCB) cells is limited by the cell dose a single unit provides recipients. Ex vivo expansion is one strategy to increase the number of cells available for transplantation. Aastrom Biosciences developed an automated continuous perfusion culture device for expansion of hematopoietic stem cells (HSCs).

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