Intensive Care Unit Admissions Among Children After Hematopoietic Stem Cell Transplantation

Abstract

We retrospectively analyzed posttransplantation events in 299 children who underwent hematopoietic stem cell transplantation between 2005 and 2011 in order to ascertain the incidence of life-threatening complications requiring pediatric intensive care unit (PICU) admission, the contributing risk factors, and the patient's long-term survival. Sixty-eight patients (23%) were admitted to the PICU. Risks factors associated with higher cumulative incidence of PICU admission on univariate analysis were nonmalignant disease, status at transplantation, type of transplant, source of stem cell, engraftment syndrome (ES), veno-occlusive disease, acute graft versus host disease (GvHD), chronic GvHD, thrombotic microangiopathy, bronchiolitis obliterans, hemorrhagic cystitis, and posterior reversible encephalopathy syndrome (PRES). On multivariate analysis, only ES, acute GvHD, transplant-associated thrombotic microangiopathy (TA-TMA), and PRES were statistically significant. The variables that had a negative impact on survival, on univariate analysis, were allogeneic transplant, age, male sex, a high O-PRISM score, a high O-PRISM3 score, engraftment failure, acute GvHD, TA-TMA, hemorrhagic cystitis, and PRES. On multivariate analysis, only age, allogeneic transplant, engraftment failure, acute GvHD, TA-TMA, and hemorrhagic cystitis had a negative impact on survival. In conclusion, our report provides new findings regarding life-threatening complications after hematopoietic transplantation for PICU admission and survival after that in a pediatric population.

Interferon-complement loop in transplant-associated thrombotic microangiopathy

“…1 Clinical outcomes for untreated TA-TMA with multiorgan dysfunction syndrome after hematopoietic stem cell transplant (HSCT) are very poor. [2][3][4][5][6][7] Complement dysregulation plays an important role in TA-TMA and complement blockade with eculizumab, a monoclonal antibody directed against C5, improves survival after TA-TMA. [8][9][10] However, some patients with TA-TMA do not have a clinical response to eculizumab, suggesting that other mechanisms of endothelial injury may be involved in the pathogenesis of thrombotic microangiopathies and could potentially serve as therapeutic targets.…”

Declining mortality rates in children admitted to ICU following HCT

“…bone marrow transplantation, critical care, ECLS, hematology, mortality, pediatrics of inotropes or vasopressors has been associated with increased mortality. 5,6 The pediatric HCT transplant unit at Rigshospitalet, Copenhagen, is a JACIE-certified tertiary center treating all Danish patients receiving allogeneic HCT at any indication and children from eastern Denmark treated with autologous HCT. Twenty-five to 30 children annually receive HCT, and the epidemiology, outcome, and prognosis of patients requiring admission to an ICU are currently unknown.…”

“…7 The mortality increases with the use of MV, number of days with MV, need for RRT and use of inotropes and vasopressors, CMV mismatch between donor and recipient, and increasing length of ICU admission. 5,8 Furthermore, we expected viral and fungal infections to be associated with a higher mortality than that of bacterial infections.…”

“…Today, the mortality rates have reportedly dropped to around 45% 3,4 . When assessing pediatric HCT patients requiring intensive care, the use of MV, number of days requiring MV, RRT, and the use of inotropes or vasopressors has been associated with increased mortality 5,6 …”

“…We reviewed all transplanted children admitted to an ICU between January 2000 December 2016 with the following hypothesis: The mortality over the 17‐year period is high but declining, with the main admission diagnosis being respiratory failure 7 . The mortality increases with the use of MV, number of days with MV, need for RRT and use of inotropes and vasopressors, CMV mismatch between donor and recipient, and increasing length of ICU admission 5,8 . Furthermore, we expected viral and fungal infections to be associated with a higher mortality than that of bacterial infections.…”