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

Matt S Zinter; Brent R Logan; Caitrin Fretham; Anil Sapru; Allistair Abraham; Mahmoud D Aljurf; Staci D Arnold; Andrew Artz; Jeffery J Auletta; Saurabh Chhabra; Edward Copelan; Christine Duncan; Robert P Gale; Eva Guinan; Peiman Hematti; Amy K Keating; David I Marks; Richard Olsson; Bipin N Savani; Celalettin Ustun; Kirsten M Williams; Marcelo C Pasquini; Christopher C Dvorak

doi:10.1016/j.bbmt.2019.09.027

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

Biol Blood Marrow Transplant. 2020 Feb;26(2):333-342. doi: 10.1016/j.bbmt.2019.09.027. Epub 2019 Sep 26.

Authors

Matt S Zinter¹, Brent R Logan², Caitrin Fretham³, Anil Sapru⁴, Allistair Abraham⁵, Mahmoud D Aljurf⁶, Staci D Arnold⁷, Andrew Artz⁸, Jeffery J Auletta⁹, Saurabh Chhabra¹⁰, Edward Copelan¹¹, Christine Duncan¹², Robert P Gale¹³, Eva Guinan¹⁴, Peiman Hematti¹⁵, Amy K Keating¹⁶, David I Marks¹⁷, Richard Olsson¹⁸, Bipin N Savani¹⁹, Celalettin Ustun²⁰, Kirsten M Williams²¹, Marcelo C Pasquini², Christopher C Dvorak²²

Affiliations

¹ Department of Pediatrics, Division of Critical Care Medicine, University of California, San Francisco, San Francisco, California. Electronic address: [email protected].
² Division of Biostatistics, Medical College of Wisconsin, Milwaukee, WI, USA; Center for International Blood and Marrow Transplant Research, Milwaukee, WI, USA.
³ Center for International Blood and Marrow Transplant Research, Milwaukee, WI, USA; National Marrow Donor Program, Minneapolis, MN, USA.
⁴ Department of Pediatrics, Division of Critical Care Medicine, University of California, Los Angeles, Los Angeles, California.
⁵ Division of Blood and Marrow Transplantation, Center for Cancer and Blood Disorders, Children's National Medical Center, Washington DC, USA.
⁶ Department of Oncology, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia.
⁷ Children's Healthcare of Atlanta, Emory University, Atlanta, GA, USA.
⁸ Department of Medicine, Section of Hematology/Oncology, University of Chicago, Chicago, Illinois.
⁹ Hematology, Oncology and Bone Marrow Transplant, Nationwide Children's Hospital, Columbus, OH, USA.
¹⁰ Division of Hematology/Oncology, Medical College of Wisconsin, Wisconsin, Milwaukee, WI, USA.
¹¹ Blood and Marrow Transplantation Program, Arthur G. James Cancer Institute, Columbus, OH, USA.
¹² Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
¹³ Department of Medicine, Division of Experimental Medicine, Hematology Research Centre, Imperial College London, London, United Kingdom.
¹⁴ Center for Clinical and Translational Research, Dana-Farber Cancer Institute, Boston, MA, USA.
¹⁵ University of Wisconsin, Madison, Wisconsin, Department of Medicine, Division of Hematology/Oncology.
¹⁶ Department of Pediatrics, Division of Blood and Marrow Transplantation, University of Colorado School of Medicine, Colorado, Denver, CO, USA.
¹⁷ University Hospitals Bristol NHS Trust, Bristol, UK.
¹⁸ Department of Laboratory Medicine, Division of Therapeutic Immunology, Karolinska Institute, Solna, Sweden.
¹⁹ Department of Medicine, Division of Hematology/Oncology, Vanderbilt University Medical Center, Nashville, TN, USA.
²⁰ Department of Medicine, Division of Hematology, Oncology, and Transplantation, University of Minnesota, Minnesota, Minneapolis, MN, USA.
²¹ Children's National Medical Center, The George Washington University Medical Center, Washington DC, USA.
²² Department of Pediatrics, Division of Allergy, Immunology, and Blood and Marrow Transplantation, University of California, San Francisco, San Francisco, California.

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 were each independently associated with PICU mortality. A multivariable model using these components identified that patients in the top quartile of risk had 3 times greater mortality than other patients (35.1% versus 11.5%, P < .001, classification accuracy 75.2%; 95% CI, 73.0% to 77.4%). These data improve our working knowledge of the factors influencing the progression of critical illness in pediatric allogeneic HCT patients. Future investigation aimed at mitigating the effect of these risk factors is warranted.

Keywords: Hematopoietic stem cell transplantation; Intensive care units; Organ dysfunction scores; Pediatric; Prognosis; Survival analysis.

Publication types

Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Child
Critical Illness*
Hematopoietic Stem Cell Transplantation*
Humans
Infant
Intensive Care Units, Pediatric
Registries
Retrospective Studies
Risk Factors

Abstract

Publication types

MeSH terms

Grants and funding