Browsing by Author "Niedzwiecki, Donna"
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Item Open Access A novel reduced-intensity conditioning regimen for unrelated umbilical cord blood transplantation in children with nonmalignant diseases.(Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 2014-03) Parikh, Suhag H; Mendizabal, Adam; Benjamin, Cara L; Komanduri, Krishna V; Antony, Jeyaraj; Petrovic, Aleksandra; Hale, Gregory; Driscoll, Timothy A; Martin, Paul L; Page, Kristin M; Flickinger, Ketti; Moffet, Jerelyn; Niedzwiecki, Donna; Kurtzberg, Joanne; Szabolcs, PaulReduced-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 2.8 years, many with severe comorbidities and prior viral infections, were enrolled in a novel RIC protocol consisting of hydroxyurea, alemtuzumab, fludarabine, melphalan, and thiotepa followed by single UCBT. Patients underwent transplantation for inherited metabolic disorders (n = 8), primary immunodeficiencies (n = 9), hemoglobinopathies (n = 4) and Diamond Blackfan anemia (n = 1). Most umbilical cord blood (UCB) units were HLA-mismatched with median infused total nucleated cell dose of 7.9 × 10(7)/kg. No serious organ toxicities were attributable to the regimen. The cumulative incidence of neutrophil engraftment was 86.4% (95% confidence interval [CI], 65% to 100%) in a median of 20 days, with the majority sustaining > 95% donor chimerism at 1 year. Cumulative incidence of acute graft-versus-host disease (GVHD) grades II to IV and III to IV by day 180 was 27.3% (95% CI, 8.7% to 45.9%) and 13.6% (95 CI, 0% to 27.6%), respectively. Cumulative incidence of extensive chronic GVHD was 9.1% (95% CI, 0% to 20.8%). The primary causes of death were viral infections (n = 3), acute GVHD (n = 1) and transfusion reaction (n = 1). One-year overall and event-free survivals were 77.3% (95% CI, 53.7% to 89.8%) and 68.2% (95% CI, 44.6% to 83.4%) with 31 months median follow-up. This is the first RIC protocol demonstrating durable UCB engraftment in children with NMD. Future risk-based modifications of this regimen could decrease the incidence of viral infections. (www.clinicaltrials.gov/NCT00744692).Item Open Access Congenital human cytomegalovirus infection is associated with decreased transplacental IgG transfer efficiency due to maternal hypergammaglobulinemia.(Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2021-07-14) Semmes, Eleanor C; Li, Shuk Hang; Hurst, Jillian H; Yang, Zidanyue; Niedzwiecki, Donna; Fouda, Genevieve G; Kurtzberg, Joanne; Walsh, Kyle M; Permar, Sallie RBackground
Placentally-transferred maternal IgG protects against pathogens in early life, yet vertically-transmitted infections can interfere with transplacental IgG transfer. Although human cytomegalovirus (HCMV) is the most common placentally-transmitted viral infection worldwide, the impact of congenital HCMV (cCMV) infection on transplacental IgG transfer has been underexplored.Methods
We evaluated total and antigen-specific maternal and cord blood IgG levels and transplacental IgG transfer efficiency in a U.S-based cohort of 93 mother-infant pairs including 27 cCMV-infected and 66 cCMV-uninfected pairs, of which 29 infants were born to HCMV-seropositive non-transmitting mothers and 37 to HCMV-seronegative mothers. Controls were matched on sex, race/ethnicity, maternal age, and delivery year.Results
Transplacental IgG transfer efficiency was decreased by 23% (95% CI 10-36%, p=0.0079) in cCMV-infected pairs and 75% of this effect (95% CI 28-174%, p=0.0085) was mediated by elevated maternal IgG levels (i.e., hypergammaglobulinemia) in HCMV-transmitting women. Despite reduced transfer efficiency, IgG levels were similar in cord blood from infants with and without cCMV infection.Conclusions
Our results indicate that cCMV infection moderately reduces transplacental IgG transfer efficiency due to maternal hypergammaglobulinemia; however, infants with and without cCMV infection had similar antigen-specific IgG levels, suggesting comparable protection from maternal IgG acquired via transplacental transfer.Item Open Access Early 18F-FDG-PET Response During Radiation Therapy for HPV-Related Oropharyngeal Cancer May Predict Disease Recurrence.(International journal of radiation oncology, biology, physics, 2020-11) Mowery, Yvonne M; Vergalasova, Irina; Rushing, Christel N; Choudhury, Kingshuk Roy; Niedzwiecki, Donna; Wu, Qiuwen; Yoo, David S; Das, Shiva; Wong, Terence Z; Brizel, David MPurpose
Early indication of treatment outcome may guide therapeutic de-escalation strategies in patients with human papillomavirus (HPV)-related oropharyngeal cancer (OPC). This study investigated the relationships between tumor volume and 18F-fluorodeoxyglucose positron emission tomography (PET) parameters before and during definitive radiation therapy with treatment outcomes.Methods and materials
Patients undergoing definitive (chemo)radiation for HPV-related/p16-positive OPC were prospectively enrolled on an institutional review board-approved study. 18F-fluorodeoxyglucose PET/computed tomography scans were performed at simulation and after 2 weeks at a dose of ∼20 Gy. Tumor volume and standardized uptake value (SUV) characteristics were measured. SUV was normalized to blood pool uptake. Tumor volume and PET parameters associated with recurrence were identified through recursive partitioning (RPART). Recurrence-free survival (RFS) and overall survival (OS) curves between RPART-identified cohorts were estimated using the Kaplan-Meier method, and Cox models were used to estimate the hazard ratios (HRs).Results
From 2012 to 2016, 62 patients with HPV-related OPC were enrolled. Median follow-up was 4.4 years. RPART identified patients with intratreatment SUVmax (normalized to blood pool SUVmean) <6.7 or SUVmax (normalized to blood pool SUVmean) ≥6.7 with intratreatment SUV40% ≥2.75 as less likely to recur. For identified subgroups, results of Cox models showed unadjusted HRs for RFS and OS (more likely to recur vs less likely) of 7.33 (90% confidence interval [CI], 2.97-18.12) and 6.09 (90% CI, 2.22-16.71), respectively, and adjusted HRs of 6.57 (90% CI, 2.53-17.05) and 5.61 (90% CI, 1.90-16.54) for RFS and OS, respectively.Conclusions
PET parameters after 2 weeks of definitive radiation therapy for HPV-related OPC are associated with RFS and OS, thus potentially informing an adaptive treatment approach.Item Open Access Image Quality and Dose Comparison of 3 Mobile Intraoperative Three-Dimensional Imaging Systems in Spine Surgery.(World neurosurgery, 2022-04) Foster, Norah; Shaffrey, Christopher; Buchholz, Avery; Turner, Raymond; Yang, Lexie Zidanyue; Niedzwiecki, Donna; Goode, AllenObjective
To evaluate radiation exposure and image quality (IQ) for 3 intraoperative imaging systems (Airo TruCT, Cios Spin, O-arm) using varying radiation dose settings in a single cadaveric model.Methods
Axial images of L4-5 instrumentation were obtained using 3 manufacturer dose protocols for each system. Measurements included scattered radiation dose, subjective and objective IQ, and estimates of patient effective dose (ED). Four images per system were selected at each dose level. Using the Likert scale (1 = best, 5 = worst), 9 reviewers rated the same 36 images. Objective IQ measures included the degree of streak artifacts (lines with incorrect data from metal objects) in each image. A composite figure of merit was derived based on ED and subjective and objective scores.Results
The best subjective IQ scores were 1.44 (Cios Spin medium dose), 1.78 (Cios Spin high dose) and 2.22 (Airo TruCT low dose). The best objective IQ scores were 87.3 (Airo TruCT) and 89.1 (Cios Spin). ED low-dose results in mSv included 1.6 (Airo TruCT), 1.9 (Cios Spin), and 3.3 (O-arm). ED high-dose results in mSv included 4.6 (Cios Spin), 9.7 (Airo TruCT), and 9.9 (O-arm). Scatter radiation measurements for low dose in μGy included 21.9 (Cios Spin), 31.8 (Airo TruCT), and 33.9 (O-arm). Scatter radiation for high dose in μGy included 55.9 (Cios Spin), 104.5 (O-arm), and 200 (Airo TruCT). The best figure of merit score was for the Airo TruCT low dose, followed by Cios Spin medium dose and high dose.Conclusions
Selection of intraoperative imaging systems requires a greater understanding of the risks and benefits of radiation exposure and IQ.Item Open Access Orthotopic Transplantation of the Full-length Porcine Intestine After Normothermic Machine Perfusion.(Transplantation direct, 2022-11) Abraham, Nader; Ludwig, Elsa K; Schaaf, Cecilia R; Veerasammy, Brittany; Stewart, Amy S; McKinney, Caroline; Freund, John; Brassil, John; Samy, Kannan P; Gao, Qimeng; Kahan, Riley; Niedzwiecki, Donna; Cardona, Diana M; Garman, Katherine S; Barbas, Andrew S; Sudan, Debra L; Gonzalez, Liara MSuccessful intestinal transplantation is currently hindered by graft injury that occurs during procurement and storage, which contributes to postoperative sepsis and allograft rejection. Improved graft preservation may expand transplantable graft numbers and enhance posttransplant outcomes. Superior transplant outcomes have recently been demonstrated in clinical trials using machine perfusion to preserve the liver. We hypothesized that machine perfusion preservation of intestinal allografts could be achieved and allow for transplantation in a porcine model.Methods
Using a translational porcine model, we developed a device for intestinal perfusion. Intestinal samples were collected at the time of organ procurement, and after 6 h of machine perfusion for gross and histologic evaluation, hourly chemistry panels were performed on the perfusate and were used for protocol optimization. Following transplantation, porcine recipient physical activity, systemic blood parameters, and vital signs were monitored for 2 d before sacrifice.Results
In initial protocol development (generation 1, n = 8 grafts), multiple metabolic, electrolyte, and acid-base derangements were measured. These factors coincided with graft and mesenteric edema and luminal hemorrhage and were addressed with the addition of dialysis. In the subsequent protocol (generation 2, n = 9 grafts), differential jejunum and ileum perfusion were observed resulting in gross evidence of ileal ischemia. Modifications in vasodilating medications enhanced ileal perfusion (generation 3, n = 4 grafts). We report successful transplantation of 2 porcine intestinal allografts after machine perfusion with postoperative clinical and gross evidence of normal gut function.Conclusions
This study reports development and optimization of machine perfusion preservation of small intestine and successful transplantation of intestinal allografts in a porcine model.