Browsing by Author "Duncan, Christine N."

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    Author Correction: Diagnosis, grading and management of toxicities from immunotherapies in children, adolescents and young adults with cancer
    (Springer Nature, 2021) Ragoonanan, Dristhi; Khazal, Sajad J.; Abdel-Azim, Hisham; McCall, David; Cuglievan, Branko; Tambaro, Francesco Paolo; Ahmad, Ali Haider; Rowan, Courtney M.; Gutierrez, Cristina; Schadler, Keri; Li, Shulin; Di Nardo, Matteo; Chi, Linda; Gulbis, Alison M.; Shoberu, Basirat; Mireles, Maria E.; McArthur, Jennifer; Kapoor, Neena; Miller, Jeffrey; Fitzgerald, Julie C.; Tewari, Priti; Petropoulos, Demetrios; Gill, Jonathan B.; Duncan, Christine N.; Lehmann, Leslie E.; Hingorani, Sangeeta; Angelo, Joseph R.; Swinford, Rita D.; Steiner, Marie E.; Hernandez Tejada, Fiorela N.; Martin, Paul L.; Auletta, Jeffery; Won Choi, Sung; Bajwa, Rajinder; Dailey Garnes, Natalie; Kebriaei, Partow; Rezvani, Katayoun; Wierda, William G.; Neelapu, Sattva S.; Shpall, Elizabeth J.; Corbacioglu, Selim; Mahadeo, Kris M.; Pediatrics, School of Medicine
    Correction to: Nature Reviews Clinical Oncology https://doi.org/10.1038/s41571-021-00474-4, published online 19 February 2021. In the original version of this Consensus Statement, the name of the author Christine N. Duncan was incorrectly written as Christine N. Duncun. In addition, Fig. 1 contained errors regarding the criteria to grade cytokine-release syndrome (CRS). “Hypotension not requiring vasopressors” has now been corrected to “hypotension requiring one vasopressor ± vasopressin” for grade 3 CRS and “hypotension requiring multiple vasopressors, not including vasopressin” for grade 4 CRS. The affiliations and Fig. 1 have been corrected in the HTML and PDF versions of the manuscript.
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    A biomarker panel for risk of early respiratory failure following hematopoietic cell transplantation
    (American Society of Hematology, 2022) Rowan, Courtney M.; Smith, Lincoln; Sharron, Matthew P.; Loftis, Laura; Kudchadkar, Sapna; Duncan, Christine N.; Pike, Francis; Carpenter, Paul A.; Jacobsohn, David; Bollard, Catherine M.; Cruz, Conrad Russell Y.; Malatpure, Abhijeet; Farag, Sherif; Renbarger, Jamie; Little, Morgan R.; Gafken, Phillip R.; Krance, Robert A.; Cooke, Kenneth R.; Paczesny, Sophie; Pediatrics, School of Medicine
    Plasma biomarkers associated with respiratory failure (RF) following hematopoietic cell transplantation (HCT) have not been identified. Therefore, we aimed to validate early (7 and 14 days post-HCT) risk biomarkers for RF. Using tandem mass spectrometry, we compared plasma obtained at day 14 post-HCT from 15 patients with RF and 15 patients without RF. Six candidate proteins, from this discovery cohort or identified in the literature, were measured by enzyme-linked immunosorbent assay in day-7 and day-14 post-HCT samples from the training (n = 213) and validation (n = 119) cohorts. Cox proportional-hazard analyses with biomarkers dichotomized by Youden's index, as well as landmark analyses to determine the association between biomarkers and RF, were performed. Of the 6 markers, Stimulation-2 (ST2), WAP 4-disulfide core domain protein 2 (WFDC2), interleukin-6 (IL-6), and tumor necrosis factor receptor 1 (TNFR1), measured at day 14 post-HCT, had the most significant association with an increased risk for RF in the training cohort (ST2: hazard ratio [HR], 4.5, P = .004; WFDC2: HR, 4.2, P = .010; IL-6: HR, 6.9, P < .001; and TFNR1: HR, 6.1, P < .001) and in the validation cohort (ST2: HR, 23.2, P = .013; WFDC2: HR, 18.2, P = .019; IL-6: HR, 12.2, P = .014; and TFNR1: HR, 16.1, P = .001) after adjusting for the conditioning regimen. Using cause-specific landmark analyses, including days 7 and 14, high plasma levels of ST2, WFDC2, IL-6, and TNFR1 were associated with an increased HR for RF in the training and validation cohorts. These biomarkers were also predictive of mortality from RF. ST2, WFDC2, IL-6 and TNFR1 levels measured early posttransplantation improve risk stratification for RF and its related mortality.
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    Diagnosis, grading and management of toxicities from immunotherapies in children, adolescents and young adults with cancer
    (Springer Nature, 2021) Ragoonanan, Dristhi; Khazal, Sajad J.; Abdel-Azim, Hisham; McCall, David; Cuglievan, Branko; Tambaro, Francesco Paolo; Ahmad, Ali Haider; Rowan, Courtney M.; Gutierrez, Cristina; Schadler, Keri; Li, Shulin; Di Nardo, Matteo; Chi, Linda; Gulbis, Alison; Shoberu, Basirate; Mireles, Maria E.; McArthur, Jennifer; Kapoor, Neena; Miller, Jeffrey; Fitzgerald, Julie C.; Tewari, Priti; Petropoulos, Demetrios; Gill, Jonathan B.; Duncan, Christine N.; Lehmann, Leslie E.; Hingorani, Sangeeta; Angelo, Joseph R.; Swinford, Rita D.; Steiner, Marie E.; Hernandez Tejada, Fiorela N.; Martin, Paul L.; Auletta, Jeffery; Choi, Sung Won; Bajwa, Rajinder; Garnes, Natalie Dailey; Kebriaei, Partow; Rezvani, Katavoun; Wierda, Willian G.; Neelapu, Sattva S.; Shpall, Elizabeth J.; Corbacioglu, Selim; Mahadeo, Kris M.; Pediatrics, School of Medicine
    Cancer immunotherapies are associated with remarkable therapeutic response rates but also with unique and severe toxicities, which potentially result in rapid deterioration in health. The number of clinical applications for novel immune effector-cell therapies, including chimeric antigen receptor (CAR)-expressing cells, and other immunotherapies, such as immune-checkpoint inhibitors, is increasing. In this Consensus Statement, members of the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network Hematopoietic Cell Transplantation-Cancer Immunotherapy (HCT-CI) Subgroup, Paediatric Diseases Working Party (PDWP) of the European Society of Blood and Marrow Transplantation (EBMT), Supportive Care Committee of the Pediatric Transplantation and Cellular Therapy Consortium (PTCTC) and MD Anderson Cancer Center CAR T Cell Therapy-Associated Toxicity (CARTOX) Program collaborated to provide updated comprehensive recommendations for the care of children, adolescents and young adults receiving cancer immunotherapies. With these recommendations, we address emerging toxicity mitigation strategies, we advocate for the characterization of baseline organ function according to age and discipline-specific criteria, we recommend early critical care assessment when indicated, with consideration of reversibility of underlying pathology (instead of organ failure scores) to guide critical care interventions, and we call for researchers, regulatory agencies and sponsors to support and facilitate early inclusion of young patients with cancer in well-designed clinical trials.
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    Extracorporeal membrane oxygenation in children receiving haematopoietic cell transplantation and immune effector cell therapy: an international and multidisciplinary consensus statement
    (Elsevier, 2022) Di Nardo, Matteo; Ahmad, Ali H.; Merli, Pietro; Zinter, Matthew S.; Lehman, Leslie E.; Rowan, Courtney M.; Steiner, Marie E.; Hingorani, Sangeeta; Angelo, Joseph R.; Abdel-Azim, Hisham; Khazal, Sajad J.; Shoberu, Basirat; McArthur, Jennifer; Bajwa, Rajinder; Ghafoor, Saad; Shah, Samir H.; Sandhu, Hitesh; Moody, Karen; Brown, Brandon D.; Mireles, Maria E.; Steppan, Diana; Olson, Taylor; Raman, Lakshmi; Bridges, Brian; Duncan, Christine N.; Choi, Sung Won; Swinford, Rita; Paden, Matt; Fortenberry, James D.; Peek, Giles; Tissieres, Pierre; De Luca, Daniele; Locatelli, Franco; Corbacioglu, Selim; Kneyber, Martin; Franceschini, Alessio; Nadel, Simon; Kumpf, Matthias; Loreti, Alessandra; Wösten-Van Asperen, Roelie; Gawronski, Orsola; Brierley, Joe; MacLaren, Graeme; Mahadeo, Kris M.; Pediatrics, School of Medicine
    Use of extracorporeal membrane oxygenation (ECMO) in children receiving hematopoietic cell transplantation (HCT) and/or Immune Effector Cells (IEC) remains controversial and evidence-based guidelines are lacking. Remarkable advancements in HCT and IEC therapies have changed expectations around reversibility of organ dysfunction and life-expectancy for affected patients. Herein, members of the Extracorporeal Life Support Organization (ELSO), Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network- (HCT and Cancer Immunotherapy Subgroup), the Pediatric Diseases Working Party of the European Society for Blood and Marrow Transplantation (EBMT), the supportive care committee of the Pediatric Transplantation and Cellular Therapy Consortium (PTCTC) and the Pediatric Intensive Care Oncology Kids in Europe Research (POKER) group of the European Society of Pediatric and Neonatal Intensive Care (ESPNIC) provide consensus recommendations on the use of ECMO in children receiving HCT-IEC. These are the first international, multi-disciplinary consensus-based recommendations on the use of ECMO in HCT-IEC pediatric patients. This manuscript may serve as a clinical decision support tool for pediatric hematologists, oncologists, and critical care physicians during the difficult decision-making process of ECMO candidacy and management. These recommendations may represent a base for future research studies focused on ECMO selection criteria and bedside management.
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    High-Frequency Oscillatory Ventilation Use and Severe Pediatric ARDS in the Pediatric Hematopoietic Cell Transplant Recipient
    (Daedalus Enterprises, 2018-04) Rowan, Courtney M.; Loomis, Ashley; McArthur, Jennifer; Smith, Lincoln S.; Gertz, Shira J.; Fitzgerald, Julie C.; Nitu, Mara E.; Moser, Elizabeth A.S.; Hsing, Deyin D.; Duncan, Christine N.; Mahadeo, Kris M.; Moffet, Jerelyn; Hall, Mark W.; Pinos, Emily L.; Tamburro, Robert F.; Cheifetz, Ira M.; Investigators of the Pediatric Acute Lung Injury and Sepsis Network; Pediatrics, School of Medicine
    INTRODUCTION: The effectiveness of high-frequency oscillatory ventilation (HFOV) in the pediatric hematopoietic cell transplant patient has not been established. We sought to identify current practice patterns of HFOV, investigate parameters during HFOV and their association with mortality, and compare the use of HFOV to conventional mechanical ventilation in severe pediatric ARDS. METHODS: This is a retrospective analysis of a multi-center database of pediatric and young adult allogeneic hematopoietic cell transplant subjects requiring invasive mechanical ventilation for critical illness from 2009 through 2014. Twelve United States pediatric centers contributed data. Continuous variables were compared using a Wilcoxon rank-sum test or a Kruskal-Wallis analysis. For categorical variables, univariate analysis with logistic regression was performed. RESULTS: The database contains 222 patients, of which 85 subjects were managed with HFOV. Of this HFOV cohort, the overall pediatric ICU survival was 23.5% (n = 20). HFOV survivors were transitioned to HFOV at a lower oxygenation index than nonsurvivors (25.6, interquartile range 21.1-36.8, vs 37.2, interquartile range 26.5-52.2, P = .046). Survivors were transitioned to HFOV earlier in the course of mechanical ventilation, (day 0 vs day 2, P = .002). No subject survived who was transitioned to HFOV after 1 week of invasive mechanical ventilation. We compared subjects with severe pediatric ARDS treated only with conventional mechanical ventilation versus early HFOV (within 2 d of invasive mechanical ventilation) versus late HFOV. There was a trend toward difference in survival (conventional mechanical ventilation 24%, early HFOV 30%, and late HFOV 9%, P = .08). CONCLUSIONS: In this large database of pediatric allogeneic hematopoietic cell transplant subjects who had acute respiratory failure requiring invasive mechanical ventilation for critical illness with severe pediatric ARDS, early use of HFOV was associated with improved survival compared to late implementation of HFOV, and the subjects had outcomes similar to those treated only with conventional mechanical ventilation.
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    Respiratory pathogens associated with intubated pediatric patients following hematopoietic cell transplant
    (Wiley, 2020-08) Gertz, Shira J.; McArthur, Jennifer; Hsing, Deyin D.; Nitu, Mara E.; Smith, Lincoln S.; Loomis, Ashley; Fitzgerald, Julie C.; Duncan, Christine N.; Mahadeo, Kris M.; Moffet, Jerelyn; Hall, Mark W.; Pinos, Emily L.; Cheifetz, Ira M.; Rowan, Courtney M.; Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network; Pediatrics, School of Medicine
    Background We describe organisms found in the respiratory tracts of a multicenter cohort of pediatric hematopoietic cell transplant (HCT) recipients with respiratory failure. Methods Twelve centers contributed up to 25 pediatric allogeneic HCT recipients requiring mechanical ventilation for respiratory failure to a retrospective database. Positive respiratory pathogens and method of obtaining sample were recorded. Outcomes were assessed using Mann-Whitney U test or chi-squared analysis. Results Of the 222 patients in the database, ages 1 month through 21 years, 34.6% had a positive respiratory culture. 105 pathogens were identified in 77 patients; of those, 48.6% were viral, 34.3% bacterial, 16.2% fungal, and 1% parasitic. PICU mortality with a respiratory pathogen was 68.8% compared to 54.9% for those without a respiratory pathogen (P = .045). Those with a positive respiratory pathogen had longer PICU length of stay, 20 days (IQR 14.0, 36.8) vs 15 (IQR 6.5, 32.0), P = .002, and a longer course of mechanical ventilation, 17 days (IQR 10, 29.5) vs 8 (3, 17), P < .0001. Method of pathogen identification, type of pathogen, and the presence of multiple pathogens were not associated with changes in PICU outcomes. Conclusions In this multicenter retrospective cohort of intubated pediatric post-HCT patients, there was high variability in the respiratory pathogens identified. Type of pathogen and method of detection did not affect PICU mortality. The presence of any organism leads to increased PICU mortality, longer PICU stay, and increased duration of mechanical ventilation suggesting that early detection and treatment of pathogens may be beneficial in this population.