Intensive care risk and long-term outcomes in pediatric allogeneic hematopoietic cell transplant recipients

Abstract

Allogeneic hematopoietic cell transplantation (HCT) can be complicated by life-threatening organ toxicity and infection necessitating intensive care. Epidemiologic data have been limited by single-center studies, poor database granularity, and a lack of long-term survivors. To identify contemporary trends in intensive care unit (ICU) use and long-term outcomes, we merged data from the Center for International Blood and Marrow Transplant Research and the Virtual Pediatric Systems databases. We identified 6995 pediatric patients with HCT aged ≤21 years who underwent first allogeneic HCT between 2008 and 2014 across 69 centers in the United States or Canada and followed patients until the year 2020. ICU admission was required for 1067 patients (8.3% by day +100, 12.8% by 1 year, and 15.3% by 5 years after HCT), and was linked to demographic background, pretransplant organ toxicity, allograft type and HLA-match, and the development of graft-versus-host disease or malignancy relapse. Survival to ICU discharge was 85.7%, but more than half of ICU survivors required ICU readmission, leading to 52.5% and 42.6% survival at 1- and 5-years post-ICU transfer, respectively. ICU survival was worse among patients with malignant disease, poor pretransplant organ function, and alloreactivity risk factors. Among 1-year HCT survivors, those who required ICU in the first year had 10% lower survival at 5 years and developed new dialysis-dependent renal failure at a greater rate (P<.001). Thus, although ICU management is common and survival to ICU discharge is high, ongoing complications necessitate recurrent ICU admission and lead to a poor 1-year outcome in select patients who are at high risk.

Graphical abstract

Figure 1.

A total of 6995 pediatric patients with allogeneic HCT were included and ∼15% required intensive care by 5 years after HCT. (A) Inclusion or exclusion flow diagram. (B) Cumulative incidence of PICU admission after allogeneic HCT. (C) Factors independently associated with post–HCT-PICU admission in multivariable competing risk-regression model.

Figure 2.

Of 1067 patients requiring intensive care, OS was ∼52% by 1 year after ICU admission. (A) Kaplan Meier estimates of OS from the time of PICU admission for all patients (top left) and malignant vs nonmalignant patients (top middle). Cumulative incidence of TRM (bottom left) and relapse (bottom middle) among patients who underwent transplantation for malignancy are also shown. (B) Factors independently associated with long-term survival from the time of PICU admission to last follow-up in multivariable Cox regression.

Figure 3.

Among 5353 patients alive at 1 year after HCT, those who survived ICU in the first year had worse 5-year survival than those who never required ICU. (A) Landmark analysis of only patients surviving to HCT day +365. Kaplan-Meier estimates of OS from transplant day +365 for all patients (top left), those with malignant disease (top middle), and those with nonmalignant disease (bottom left), stratified by need for intensive care in the first year after HCT. Cumulative incidence of TRM (bottom middle) among patients who underwent transplantation for malignancy is also shown. (B) Among those alive at HCT day +365, factors independently associated with long-term survival from transplant day +365 to last follow-up in multivariable Cox regression.