Comprehensive Prognostication in Critically Ill Pediatric Hematopoietic Cell Transplant Patients: Results from Merging the Center for International Blood and Marrow Transplant Research (CIBMTR) and Virtual Pediatric Systems (VPS) Registries

Abstract

Critically ill pediatric allogeneic hematopoietic cell transplant (HCT) patients may benefit from early and aggressive interventions aimed at reversing the progression of multiorgan dysfunction. Therefore, we evaluated 25 early risk factors for pediatric intensive care unit (PICU) mortality to improve mortality prognostication. We merged the Virtual Pediatric Systems and Center for International Blood and Marrow Transplant Research databases and analyzed 936 critically ill patients 21 years of age who had undergone allogeneic HCT and subsequently required PICU admission between January 1, 2009, and December 31, 2014. Of 1532 PICU admissions, the overall PICU mortality rate was 17.4% (95% confidence interval [CI], 15.6% to 19.4%) but was significantly higher for patients requiring mechanical ventilation (44.0%), renal replacement therapy (56.1%), or extracorporeal life support (77.8%). Mortality estimates increased significantly the longer that patients remained in the PICU. Of 25 HCT-and PICU-specific characteristics available at or near the time of PICU admission, moderate/severe pre-HCT renal injury, pre-HCT recipient cytomegalovirus seropositivity, <100-day interval between HCT and PICU admission, HCT for underlying acute myeloid leukemia, and greater admission organ dysfunction as approximated by the Pediatric Risk of Mortality 3 score

The pulmonary metatranscriptome prior to pediatric HCT identifies post-HCT lung injury

“…3,4 Unfortunately, outcomes for lung-injured pediatric HCT recipients are poor, with ;40% mortality when mechanical ventilation is required and .60% mortality in the setting of acute respiratory distress syndrome. [5][6][7][8] Accordingly, it is imperative to identify factors associated with the development of post-HCT lung injury to facilitate prevention, early detection, and biology-targeted treatments. Clinical factors associated with the development of post-HCT lung injury in children include impairment on pre-HCT pulmonary function tests; abnormalities on pre-HCT high-resolution chest tomography (HRCT); the use of myeloablative conditioning and/or specific chemotherapeutic agents, including busulfan, bleomycin, and total body irradiation; and the use of HLA-mismatched or T-cell-replete allografts.…”

Perspective: A Framework to Screen Pediatric and Adolescent Hematopoietic Cellular Therapy Patients for Organ Dysfunction: Time for a Multi-Disciplinary and Longitudinal Approach

“…The Center for International Blood and Marrow Transplant Research (CIBMTR) and Virtual Pediatric Systems capture discipline specific data in disparate registries. Attempts to merge these registries to advance our understanding of pediatric HCT patients who require PICU care have been an important step forward to improve our working knowledge of the factors influencing the progression of critical illness in pediatric allogeneic HCT patients ( 77 ). However, even these efforts are limited by the limitations of current data fields which may not capture detailed organ specific information, in particular among Pediatric HCT patients who do not require PICU admission or who do become critically ill but proceed to palliative care in lieu of escalation of care.…”

Case Report: Management Approach and Use of Extracorporeal Membrane Oxygenation for Diffuse Alveolar Hemorrhage After Pediatric Hematopoietic Cell Transplant

“…The medical complexity of HCT care inherently raises the PICU mortality when compared to the general population ( 19 ). As such, underlying malignancy and HCT are considered contraindications for ECMO support by most centers.…”

“…Likewise, technological advances in ECMO support and improvements in the management of mechanical ventilated patients have resulted in improved ECMO outcomes ( 23 , 24 ). Zinter et al found a 22% PICU survival in HCT patients supported with ECMO from 2009 to 2014 ( 19 ). Most recently, in a review of HCT patients supported with ECMO from 2011 to 2018, Steppan et al found that 4 out of 8 patients survived to hospital discharge ( 25 ).…”