Browsing by Author "Mahadeo, Kris M."
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Item 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 MedicineCorrection 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.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 Early Cumulative Fluid Balance and Outcomes in Pediatric Allogeneic Hematopoietic Cell Transplant Recipients With Acute Respiratory Failure: A Multicenter Study(Frontiers Media, 2021-07-20) Sallee, Colin J.; Smith, Lincoln S.; Rowan, Courtney M.; Heckbert, Susan R.; Angelo, Joseph R.; Daniel, Megan C.; Gertz, Shira J.; Hsing, Deyin D.; Mahadeo, Kris M.; McArthur, Jennifer A.; Fitzgerald, Julie C.; Pediatrics, School of MedicineObjectives: To evaluate the associations between early cumulative fluid balance (CFB) and outcomes among critically ill pediatric allogeneic hematopoietic cell transplant (HCT) recipients with acute respiratory failure, and determine if these associations vary by treatment with renal replacement therapy (RRT). Methods: We performed a secondary analysis of a multicenter retrospective cohort of patients (1mo - 21yrs) post-allogeneic HCT with acute respiratory failure treated with invasive mechanical ventilation (IMV) from 2009 to 2014. Fluid intake and output were measured daily for the first week of IMV (day 0 = day of intubation). The exposure, day 3 CFB (CFB from day 0 through day 3 of IMV), was calculated using the equation [Fluid in - Fluid out] (liters)/[PICU admission weight] (kg)*100. We measured the association between day 3 CFB and PICU mortality with logistic regression, and the rate of extubation at 28 and 60 days with competing risk regression (PICU mortality = competing risk). Results: 198 patients were included in the study. Mean % CFB for the cohort was positive on day 0 of IMV, and increased further on days 1-7 of IMV. For each 1% increase in day 3 CFB, the odds of PICU mortality were 3% higher (adjusted odds ratio (aOR) 1.03, 95% CI 1.00-1.07), and the rate of extubation was 3% lower at 28 days (adjusted subdistribution hazard ratio (aSHR) 0.97, 95% CI 0.95-0.98) and 3% lower at 60 days (aSHR 0.97, 95% CI 0.95-0.98). When day 3 CFB was dichotomized, 161 (81%) had positive and 37 (19%) had negative day 3 CFB. Positive day 3 CFB was associated with higher PICU mortality (aOR 3.42, 95% CI 1.48-7.87) and a lower rate of extubation at 28 days (aSHR 0.30, 95% CI 0.18-0.48) and 60 days (aSHR 0.30, 95% 0.19-0.48). On stratified analysis, the association between positive day 3 CFB and PICU mortality was significantly stronger in those not treated with RRT (no RRT: aOR 9.11, 95% CI 2.29-36.22; RRT: aOR 1.40, 95% CI 0.42-4.74). Conclusions: Among critically ill pediatric allogeneic HCT recipients with acute respiratory failure, positive and increasing early CFB were independently associated with adverse outcomes.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 Fluid Overload in Pediatric Acute Respiratory Distress Syndrome after Allogeneic Hematopoietic Cell Transplantation(Thieme, 2022-10-11) Sallee, Colin J.; Fitzgerald, Julie C.; Smith, Lincoln S.; Angelo, Joseph R.; Daniel, Megan C.; Gertz, Shira J.; Hsing, Deyin D.; Mahadeo, Kris M.; McArthur, Jennifer A.; Rowan, Courtney M.; Pediatric Acute Lung Injury Sepsis Investigators (PALISI) Network; Pediatrics, School of MedicineThe aim of the study is to examine the relationship between fluid overload (FO) and severity of respiratory dysfunction in children posthematopoietic cell transplantation (HCT) with pediatric acute respiratory distress syndrome (PARDS). This investigation was a secondary analysis of a multicenter retrospective cohort of children (1month to 21 years) postallogeneic HCT with PARDS receiving invasive mechanical ventilation (IMV) from 2009 to 2014. Daily FO % (FO%) and daily oxygenation index (OI) were calculated for each patient up to the first week of IMV (day 0 = intubation). Linear mixed-effect regression was employed to examine whether FO% and OI were associated on any day during the study period. In total, 158 patients were included. Severe PARDS represented 63% of the cohort and had higher mortality (78 vs. 42%, p <0.001), fewer ventilator free days at 28 (0 [IQR: 0-0] vs. 14 [IQR: 0-23], p <0.001), and 60 days (0 [IQR: 0-27] v. 45 [IQR: 0-55], p <0.001) relative to nonsevere PARDS. Increasing FO% was strongly associated with higher OI ( p <0.001). For children with 10% FO, OI was higher by nearly 5 points (adjusted β , 4.6, 95% CI: [2.9, 6.3]). In subgroup analyses, the association between FO% and OI was strongest among severe PARDS ( p <0.001) and during the first 3 days elapsed from intubation ( p <0.001). FO% was associated with lower PaO 2 /FiO 2 (adjusted β , -1.92, 95% CI: [-3.11, -0.73], p = 0.002), but not mean airway pressure ( p = 0.746). In a multicenter cohort of children post-HCT with PARDS, FO was independently associated with oxygenation impairment. The associations were strongest among children with severe PARDS and early in the course of IMV.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 Noninvasive Ventilation Exposure Prior to Intubation in Pediatric Hematopoietic Cell Transplant Recipients(Daedalus Enterprises, 2022) Cater, Daniel T.; Fitzgerald, Julie C.; Gertz, Shira J.; McArthur, Jennifer A.; Daniel, Megan C.; Mahadeo, Kris M.; Hsing, Deyin D.; Smith, Lincoln S.; Pike, Francis; Rowan, Courtney M.; Pediatrics, School of MedicineBackground: Noninvasive ventilation (NIV) has become more studied in immunocompromised patients. However, it has not been studied in hematopoietic cell transplantation (HCT) recipients, who have higher mortality and higher pulmonary complication rates than other immunocompromised patients. This population may be prone to negative effects from this treatment modality. The aim of this study was to determine whether NIV use is associated with worse outcomes in this vulnerable patient population. Methods: A secondary analysis of a retrospective multi-center database was performed. Twelve pediatric ICUs across the United States enrolled HCT subjects from 2009-2014 that were admitted to the pediatric ICU (PICU) with the diagnosis of acute respiratory failure. Subjects exposed to NIV prior to intubation were compared against those not exposed to NIV. Our primary outcome was all-cause mortality at 90 d; secondary outcomes included ventilator-free days (VFD) at 28 d and development of pediatric ARDS. Multivariable logistic and linear regression models were constructed using variables significant on univariable analysis. Results: Two-hundred eleven subjects were included. Of these, 82 (39%) received NIV prior to intubation. Those that received NIV prior to intubation were older (13 vs 6 y, P < .001) and more commonly diagnosed with respiratory distress (90% vs 74%, P = .004). On multivariable analysis, NIV use prior to intubation was associated with a higher PICU mortality (hazard ratio 1.51 [95% CI 1.18-2.28], P = .02) and fewer VFD at 28 d (β -3.50 [95% CI -6.09 to 0.91], P = .008). Those with NIV exposure prior to intubation also had higher rates of development of pediatric ARDS (95% vs 78%, P = .001). Conclusions: In this cohort of children post-HCT, NIV use prior to intubation was associated with worse outcomes. The benefits and risks of NIV in this patient population should be carefully evaluated prior to its use, and careful patient selection is crucial for its optimal utilization.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.Item Risk Factors for Noninvasive Ventilation Failure in Children Post-Hematopoietic Cell Transplant(Frontiers Media, 2021-05-27) Rowan, Courtney M.; Fitzgerald, Julie C.; Agulnik, Asya; Zinter, Matt S.; Sharron, Matthew P.; Slaven, James E.; Kreml, Erin M.; Bajwa, Rajinder P.S.; Mahadeo, Kris M.; Moffet, Jerelyn; Tarquinio, Keiko M.; Steiner, Marie E.; Pediatrics, School of MedicineRationale: Little is known on the use of noninvasive ventilation (NIPPV) in pediatric hematopoietic cell transplant (HCT) patients. Objective: We sought to describe the landscape of NIPPV use and to identify risk factors for failure to inform future investigation or quality improvement. Methods: This is a multicenter, retrospective observational cohort of 153 consecutive children post-HCT requiring NIPPV from 2010-2016. Results: 97 (63%) failed NIPPV. Factors associated with failure on univariate analysis included: longer oxygen use prior to NIPPV (p=0.04), vasoactive agent use (p<0.001), and higher respiratory rate at multiple hours of NIPPV use (1hr p=0.02, 2hr p=0.04, 4hr p=0.008, 8hr p=0.002). Using respiratory rate at 4 hours a multivariable model was constructed. This model demonstrated high ability to discriminate NIPPV failure (AUC=0.794) with the following results: respiratory rate >40 at 4 hours [aOR=6.3 9(95% CI: 2.4, 16.4), p<0.001] and vasoactive use [aOR=4.9 (95% CI: 1.9, 13.1), p=0.001]. Of note, 11 patients had a cardiac arrest during intubation (11%) and 3 others arrested prior to intubation. These 14 patients were closer to HCT [14 days (IQR:4, 73) vs 54 (IQR:21,117), p<0.01] and there was a trend toward beginning NIPPV outside of the PICU and arrest during/prior to intubation (p=0.056). Conclusions: In this cohort respiratory rate at 4 hours and vasoactive use are independent risk factors of NIPPV failure. An objective model to predict which children may benefit from a trial of NIPPV, may also inform the timing of both NIPPV initiation and uncomplicated intubation.