Pediatric oncology patients have increased risk for critical illness; outcomes are well described in high-income countries (HICs); however, data is limited for low- and middle-income countries (LMICs). We systematically searched PubMed, EMBASE, Web of Science, CINAHL and Global Health databases for articles in 6 languages describing mortality in children with cancer admitted to intensive care units (ICUs) in LMICs. Two investigators independently assessed eligibility, data quality, and extracted data. We pooled ICU mortality estimates using random effect models. Of 3641 studies identified, 22 studies were included, covering 4803 ICU admissions. Overall pooled mortality was 30.3 % [95 % Confidence-interval (CI) 21.7-40.6 %]. Mechanical ventilation [odds ratio (OR) 12.2, 95 %CI:6.2-24.0, p-value<0.001] and vasoactive infusions [OR 6.3 95 %CI:3.3-11.9, p-value<0.001] were associated with ICU mortality. ICU mortality among pediatric oncology patients in LMICs is similar to that in HICs, however, this review likely underestimates true mortality due to underrepresentation of studies from low-income countries.

In the current Research Topic, Critical Complications in Pediatric Oncology and Hematopoietic Cell Transplant, Volume II, there is a continuation of the themes of improving outcomes and strengthening collaboration. This collection contains 21 publications from 195 authors representing 22 different countries on 5 continents (Figure 1). Volume II provides ongoing evidence that the field of pediatric onco-critical care is not going back to the era of the selffulfilling prophecy that critically ill children with cancer have abysmal outcomes rendering use of critical care resources futile.Knowing which HCT patients are at highest risk for requiring ICU care would be very valuable for clinicians. Using data from pediatric oncology patients in the Colorado Sepsis and Treatment Registry, serum lactate within 2 hours of presentation was found to be predictive of clinical deterioration events (OR 1.82, p<0.001), need for ICU admission (OR 1.68, p<0.001) and bacteremia (OR 1.49, p<0.001) [Slatnick et al]. Johnson et al performed a single center retrospective review of pediatric patients who received HCT at their institution between January 2015-December 2020 [Johnson et al]. Risk factors for PICU admission were: 1) younger age; 2) lower weight; 3) inborn error of metabolism as a reason for HCT and 4) use of busulfan conditioning. There was overlap in these results with those found by Zinter et al in a multi-center study merging the Center for International Bone Marrow Transplantation (CIBMTR) and Virtual PICU Performance System (VPS) databases. They also found younger age and inborn errors of metabolism as risk factors for requiring ICU care (17). However, there was disagreement where Zinter found pre-HCT organ dysfunction was associated with increased requirement for ICU admission, whereas Johnson did not. This may represent an improvement over time in managing complex patients during HCT versus differences in study design. A better understand organ dysfunction in these unique patients is imperative for continued improvements in outcomes.Accurate data surrounding the risks and benefits of ICU therapies will lead to better informed decisions regarding PICU interventions. In a retrospective single center study, Schober et al found that admissions for respiratory support (OR 1.04, p=0.04) and dialysis (OR 1.21, p=0.03) increased 6-month mortality compared to other reasons for PICU admission [Schober et al]. In a multi-variate analysis of pediatric oncology patients, hemato-oncology diagnosis, number of failing organs at baseline and unplanned admissions were associated with development of new or progressive multi-organ failure [Soeteman et al]. Data from the Health Facts (Cerner Corporation, Kansas City, MO) database containing 473 pediatric HCT patients found 11% required positive pressure ventilation, 25% received vasopressor medications and 3% received dialysis. Decreased survival was seen in allogeneic transplant (p<0.01), graft versus host disease (p=0.02), infection (p<0.01) and need for ICU therapies (p<0.01) [Olson et al]. Interestingly, survival improved over time for patients who received allogeneic transplants. The improved survival in the later era of the study was associated with decreased infections and increased use of vasopressor agents. The improvement in survival could represent a change in practice due to recent publications addressing the detrimental effects of fluid overload in HCT patients (16,18) with a shift towards earlier use of vasopressors rather than fluid resuscitation.Chimeric antigen receptor therapy, CAR-T, is being used in a growing number of cancers. However, it carries an increased risk for life threatening complications and critical illness. In a multi-center study, Ragoonanan et al compared PICU courses for pediatric ALL patients who were receiving conventional therapy vs those who received tisagenlecleucel [Ragoonanan et al]. They found PICU resource utilization between the 2 groups to be similar. The authors concluded that improved management of complications and need for ICU care should decline over time making CAR-T an important therapy to pursue, potentially beyond high resource settings.Cardenas-Aguirre et al show us that critically ill pediatric oncology patients in resource limited-settings can have PICU outcomes similar to those seen in high income countries [Cardenas-Aguirre et al]. In their dedicated pediatric oncology hospital in Mexico, they describe overall PICU mortality of 6.9% with mortality for unplanned PICU admissions of 9.1%. This is similar to that described in high income countries (19,20) The authors felt their center's low mortality was likely the result of implementing a number of quality improvement practices aimed at earlier recognition of deterioration allowing for earlier interventions.Endotheliopathy has been considered an underlying cause of multiple complications of HCT including sinusoidal obstructive disorder (SOS), transplant associated -thrombotic microangiopathy (TA-TMA), diffuse alveolar hemorrhage (DAH), pulmonary hypertension and graft-versus-host disease (GVHD). In a review article, Pace et al explore the interaction between host and donor endothelial cells in hematopoietic cell transplantation as well as solid organ transplant [Pace et al]. Kafa et al described their single center experience with TA-TMA [Kafa et al]. Factors associated with developing TA-TMA were allogeneic transplant and use of total body irradiation as part of the conditioning regimen. Despite a good response to therapy, their patients experienced several complications with the most frequent being renal impairment and chronic kidney disease in 80%. This collection also addresses strategies for improving management of respiratory failure, a deadly complication. Pediatric HCT patients have been shown to have a high rate of periintubation cardiac arrest (9) which may represent a delay in intubation timing. Hume et al undertook a...

Background: Sepsis is a common and serious complication in pediatric hematology oncology (PHO) patients. The Endothelial Activation and Stress Index (EASIX) score offers a potentially accessible tool for risk stratification in septic patients. Our objective was to evaluate the association of the EASIX score with adverse clinical outcomes among septic PHO patients. Methods: A retrospective review was conducted for all PHO patients admitted to the intensive care unit (ICU) with sepsis from July 2022 to December 2024. Results: A total of 53 patients with 65 sepsis events were included in this analysis. The median age was 14.9 [IQR 9.9] y and the most common disease was hematologic malignancy. In our cohort, 60% needed vasopressors, 36% required invasive mechanical ventilation, and 22% underwent renal replacement therapy (RRT). Log2-EASIX > 2.5 was associated with higher vasopressor requirements (87% versus 45% in the low log2-EASIX group, p = 0.001) and an increased need for RRT (39% versus 12%, p = 0.024). Septic PHO patients with log2-EASIX > 2.5 were 6.9 times more likely to require vasopressor support [(95% CI 1.7–27.8) p = 0.007]. In addition, PHO patients with log2-EASIX > 2.5 had a longer ICU stay (7 d versus 2 d in the low log2-EASIX group, p = 0.024) and an extended overall hospitalization (33 d versus 25 d, p = 0.029). Conclusions: A higher EASIX score was associated with adverse outcomes in critically ill septic PHO patients. Our findings suggest that the EASIX score can be used as a tool for identifying septic patients at an increased risk of clinical deterioration and poor outcomes. Prospective studies in larger cohorts are warranted to validate and expand upon these findings.

Introduction: Retrospective data suggest that pediatric hematopoietic cell transplant (HCT) patients placed on non-invasive ventilation (NIV) prior to intubation have increased risk of mortality compared to patients who are intubated earlier in their course. The HCT-CI subgroup of the PALISI Network set out to gain a better understanding of factors that influence clinician’s decisions surrounding timing of intubation of pediatric HCT patients.Methods: We validated and distributed a brief survey exploring potential factors that may influence clinician’s decisions around timing of intubation of pediatric HCT patients with acute lung injury (ALI).Results: One hundred and four of the 869 PALISI Network’s members responded to the survey; 97 of these respondents acknowledged caring for HCT patients and were offered the remainder of the survey. The majority of respondents were PICU physicians (96%), with a small number of Advanced Practice Providers and HCT physicians. As expected, poor prognosis categories were perceived as a factors that delay timing to intubation whereas need for invasive procedures was perceived as a factor shortening timing to intubation. Concerns for oxygen toxicity or NIV-associated lung injury were not believed to influence timing of intubation.Discussion: Our survey indicates increased risk of ALI from prolonged NIV and oxygen toxicity in HCT patients are not a concern for most clinicians. Further education of pediatric ICU clinicians around these risk factors could lead to improvement in outcomes and demands further study. Additionally, clinicians identified concerns for the patient’s poor prognosis as a common reason for delayed intubation.