0
selected
-
1.
Intensive Care Risk and Long-Term Outcomes in Pediatric Allogeneic Hematopoietic Cell Transplant Recipients
Zinter, M. S., Brazauskas, R., Strom, J., Chen, S., Bo-Subait, S., Sharma, A., Beitinjaneh, A., Dimitrova, D., Guilcher, G., Preussler, J. M., et al
Blood advances. 2023
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 ICU utilization 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 6,995 pediatric HCT patients age ≤21 years who underwent 1st allogeneic HCT between 2008-2014 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 post-HCT), and was linked to demographic background, pre-transplant 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 pre-transplant 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<0.001). Thus, while 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 high-risk patients.
-
2.
Non-infectious pulmonary toxicity after allogeneic hematopoietic cell transplantation
Patel, S. S., Ahn, K. W., Khanal, M., Bupp, C., Allbee-Johnson, M., Majhail, N. S., Hamilton, B. K., Rotz, S. J., Hashem, H., Beitinjaneh, A., et al
Transplantation and cellular therapy. 2022
Abstract
Non-infectious pulmonary toxicity (NPT) is a significant complication of allogeneic hematopoietic cell transplantation (alloHCT) and includes idiopathic pneumonia syndrome (IPS), diffuse alveolar hemorrhage (DAH), and cryptogenic organizing pneumonia (COP) with an overall incidence ranging 1-15% in different case series and variable mortality rates. A registry study of the epidemiology and outcomes of NPT after alloHCT has not been conducted. The primary objective was to assess the incidence of and risk factors for IPS, DAH, and COP; the secondary objective was to assess overall survival (OS) in patients developing NPT. This retrospective study included adult patients who underwent alloHCT between 2008 and 2017 and reported to the Center for International Blood and Marrow Transplant Research (CIBMTR®). Multivariable Cox proportional hazards regression models were developed to identify the risk factors for development of NPT and for OS, by including pre-transplant clinical variables and time-dependent variables of neutrophil and platelet recovery, and acute GVHD post-transplant. This study included 21,574 adult patients, with a median age of 55 years. Per the HCT-Comorbidity Index (HCT-CI), 24% and 15% patients had moderate and severe pulmonary comorbidity, respectively. The cumulative incidence of NPT at 1-year was 8.1% (95% confidence interval [95CI], 7.7-8.5%). Individually, 1-year cumulative incidence of IPS, DAH, and COP was 4.9% (95CI, 4.7-5.2%), 2.1% (95CI, 1.9-2.3%), and 0.7% (95CI, 0.6-0.8%), respectively. Multivariable analysis showed severe pulmonary comorbidity, grade II-IV acute GVHD, mismatched unrelated donor and cord blood transplant, and HCT-CI score ≥1 significantly increased the risk of NPT. In contrast, alloHCT performed in ≥2014, non-TBI and TBI-based non-myeloablative conditioning and platelet recovery were associated with a decreased risk. In a landmark analysis at day+100 post-transplant, the risk of DAH was significantly lower in patients who had platelet recovery by day+100. Multivariable analysis for OS demonstrated that NPT significantly increased the mortality risk (HR 4.2, p<0.0001).
-
3.
Underdiagnosed veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) as a major cause of multi-organ failure in acute leukemia transplant patients: an analysis from the EBMT Acute Leukemia Working Party
Bazarbachi, A. H., Al Hamed, R., Labopin, M., Halaburda, K., Labussiere, H., Bernasconi, P., Schroyens, W., Gandemer, V., Schaap, N. P. M., Loschi, M., et al
Bone marrow transplantation. 2020
Abstract
Allogeneic hematopoietic cell transplantation (alloHCT) is a complex, potentially fatal therapy featuring a myriad of complications. Triggering event(s) of such complications vary significantly, but often a so-called "multi-organ failure" (MOF) is reported as the leading cause of death. The identification of the exact trigger of MOF is critical towards early and disease-specific intervention to improve outcome. We examined data from 202 alloHCT patients reported to have died of MOF from the EBMT registry aiming to determine their exact cause of death focusing on veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) due to its life-threatening, often difficult to capture yet preventable nature. We identified a total of 70 patients (35%) for whom VOD/SOS could be considered as trigger for MOF and leading cause of death, among which 48 (69%) were previously undiagnosed. Multivariate analysis highlighted history of hepatic comorbidity or gentuzumab use and disease status beyond CR1 as the only significant factors predictive of VOD/SOS incidence (OR?=?6.6; p?=?0.001 and OR?=?3.3; p?=?0.004 respectively). VOD/SOS-related MOF was widely under-reported, accounting for 27% of deaths attributed to MOF of unknown origin without a previous VOD/SOS diagnosis. Our results suggest most missed cases developed late VOD/SOS beyond 21 days post-alloHCT, highlighting the importance of the newly revised EBMT criteria.
-
4.
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
Zinter, M. S., Logan, B. R., Fretham, C., Sapru, A., Abraham, A., Aljurf, M. D., Arnold, S. D., Artz, A., Auletta, J. J., Chhabra, S., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2019
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 PICU mortality in order to improve mortality prognostication. We merged the Virtual Pediatric Systems (VPS, LLC) and Center For International Blood and Marrow Transplant Research (CIBMTR) 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 1,532 PICU admissions, the overall PICU mortality rate was 17.4% (95% CI 15.6%-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/near the time of PICU admission, moderate/severe pre-HCT renal injury, pre-HCT recipient cytomegalovirus (CMV) seropositivity, <100 day interval between HCT and PICU admission, HCT for underlying Acute Myeloid Leukemia (AML), and greater admission organ dysfunction as approximated by the PRISM-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 three times greater mortality than other patients (35.1% vs. 11.5%, p<0.001, classification accuracy 75.2%, 95% CI 73.0-77.4%). 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.