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Item Candidacy for Extracorporeal Life Support in Children After Hematopoietic Cell Transplantation: A Position Paper From the Pediatric Acute Lung Injury and Sepsis Investigators Network's Hematopoietic Cell Transplant and Cancer Immunotherapy Subgroup(Wolters Kluwer, 2022) Zinter, Matt S.; McArthur, Jennifer; Duncan, Christine; Adams, Roberta; Kreml, Erin; Dalton, Heidi; Abdel-Azim, Hisham; Rowan, Courtney M.; Gertz, Shira J.; Mahadeo, Kris M.; Randolph, Adrienne G.; Rajapreyar, Prakadeshwari; Steiner, Marie E.; Lehmann, Leslie; Hematopoietic Cell Transplant and Cancer Immunotherapy Subgroup of the PALISI Network; Pediatrics, School of MedicineObjectives: The last decade has seen improved outcomes for children requiring extracorporeal life support as well as for children undergoing hematopoietic cell transplantation. Thus, given the historically poor survival of hematopoietic cell transplantation patients using extracorporeal life support, the Pediatric Acute Lung Injury and Sepsis Investigators' hematopoietic cell transplantation and cancer immunotherapy subgroup aimed to characterize the utility of extracorporeal life support in facilitating recovery from critical cardiorespiratory illnesses in pediatric hematopoietic cell transplantation patients. Data sources: All available published data were identified using a set of PubMed search terms for pediatric extracorporeal life support and hematopoietic cell transplantation. Study selection: All articles that provided original reports of pediatric hematopoietic cell transplantation patients who underwent extracorporeal life support were included. Sixty-four manuscripts met search criteria. Twenty-four were included as primary reports of pediatric hematopoietic cell transplantation patients who underwent extracorporeal life support (11 were single case reports, four single institution case series, two multi-institution case series, and seven registry reports from Extracorporeal Life Support Organization, Pediatric Heath Information System, and Virtual Pediatric Systems). Data extraction: All 24 articles were reviewed by first and last authors and a spread sheet was constructed including sample size, potential biases, and conclusions. Data synthesis: Discussions regarding incorporation of available evidence into our clinical practice were held at biannual meetings, as well as through email and virtual meetings. An expert consensus was determined through these discussions and confirmed through a modified Delphi process. Conclusions: Extracorporeal life support in hematopoietic cell transplantation patients is being used with increasing frequency and potentially improving survival. The Pediatric Acute Lung Injury and Sepsis Investigators hematopoietic cell transplantation-cancer immunotherapy subgroup has developed a framework to guide physicians in decision-making surrounding extracorporeal life support candidacy in pediatric hematopoietic cell transplantation patients. In addition to standard extracorporeal life support considerations, candidacy in the hematopoietic cell transplantation population should consider the following six factors in order of consensus agreement: 1) patient comorbidities; 2) underlying disease necessitating hematopoietic cell transplantation; 3) hematopoietic cell transplantation toxicities, 4) family and patient desires for goals of care; 5) hematopoietic cell transplantation preparatory regimen; and 6) graft characteristics. Although risk assessment may be individualized, data are currently insufficient to clearly delineate ideal candidacy. Therefore, we urge the onco-critical care community to collaborate and capture data to provide better evidence to guide physicians' decision-making in the future.Item 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 MedicineCancer 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.Item 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 MedicineUse 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.Item High Levels of Morbidity and Mortality Among Pediatric Hematopoietic Cell Transplant Recipients With Severe Sepsis: Insights From the Sepsis PRevalence, OUtcomes, and Therapies International Point Prevalence Study*(Wolters Kluwer, 2017-12-01) Lindell, Robert B.; Gertz, Shira J.; Rowan, Courtney M.; McArthur, Jennifer; Beske, Florian; Plunkett, Adrian; Weiss, Scott L.; Thomas, Neal J.; Nadkarni, Vinay M.; Fitzgerald, Julie C.; Pediatrics, School of MedicineObjectives: Pediatric severe sepsis is a major cause of morbidity and mortality worldwide, and hematopoietic cell transplant patients represent a high-risk population. We assessed the epidemiology of severe sepsis in hematopoietic cell transplant patients, describing patient outcomes compared with children with no history of hematopoietic cell transplant. Design: Secondary analysis of the Sepsis PRevalence, OUtcomes, and Therapies point prevalence study, comparing demographics, sepsis etiology, illness severity, organ dysfunction, and sepsis-related treatments in patients with and without hematopoietic cell transplant. The primary outcome was hospital mortality. Multivariable logistic regression models were used to determine adjusted differences in mortality. Setting: International; 128 PICUs in 26 countries. Patients: Pediatric patients with severe sepsis prospectively identified over a 1-year period. Interventions: None. Measurements and Main Results: In patients with severe sepsis, 37/567 (6.5%) had a history of hematopoietic cell transplant. Compared with patients without hematopoietic cell transplant, hematopoietic cell transplant patients had significantly higher hospital mortality (68% vs 23%; p < 0.001). Hematopoietic cell transplant patients were more likely to have hospital acquired sepsis and had more preexisting renal and hepatic dysfunction than non–hematopoietic cell transplant patients with severe sepsis. History of hematopoietic cell transplant, renal replacement therapy, admission from inpatient floor, and number of organ dysfunctions at severe sepsis recognition were independently associated with hospital mortality in multivariable analysis; hematopoietic cell transplant conferred the highest odds of mortality (odds ratio, 4.00; 95% CI, 1.78–8.98). In secondary analysis of hematopoietic cell transplant patients compared with other immunocompromised patients with severe sepsis, history of hematopoietic cell transplant remained independently associated with hospital mortality (odds ratio, 3.03; 95% CI, 1.11–8.27). Conclusions: In an international study of pediatric severe sepsis, history of hematopoietic cell transplant is associated with a four-fold increased odds of hospital mortality after adjustment for potential measured confounders. Hematopoietic cell transplant patients more often originated from within the hospital compared to children with severe sepsis without hematopoietic cell transplant, possibly providing an earlier opportunity for sepsis recognition and intervention in this high-risk population.Item 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 MedicineINTRODUCTION: 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.Item Non-infectious pulmonary complications of hematopoietic stem cell transplantation(Thieme, 2014-09) Rowan, Courtney; Baloglu, Orkun; McArthur, Jennifer; Pediatrics, School of MedicineNoninfectious pulmonary complications of hematopoietic stem cell transplant are currently more prevalent than infectious complications. Unfortunately, the pathophysiology basis is not completely understood. However, there is a string association with graft-versus-host disease for many of them. Therefore, an important component of their pathophysiology is likely an allo-immune response. There is much research that needs to be conducted to improve the less than optimal outcomes for these disorders.Item 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 MedicineBackground 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.