Acute Non-Infectious Complications of Pediatric Hematopoietic Stem Cell Transplantation: An in-Hospital Nationwide Study in the United States from 2001-2019

Introduction

Hematopoietic stem cell transplantation (HSCT) is an effective treatment for malignant and non-malignant disorders and may be the only curative option for some diseases. Although overall outcomes of HSCT in pediatrics have improved HSCT is still associated with high morbidity and mortality. Toxicity following HSCT can virtually affect any organ and occur at different steps in the process. Early complications are to occur in the first 100 days post transplant. In this study we aimed to describe the frequency of early complications following HSCT and possible risk factors associated with increased ICU care and mortality.

Methods

With IRB approval, the Pediatric Health Information Systems (PHIS) database was queried to analyze information of all HSCT performed admitted between January 2001 and December 2019. The PHIS database is a comprehensive pediatric database that includes inpatient encounters for more than 52 children’s hospitals. We extracted relevant ICD-9 and 10 diagnoses, procedure codes, and medications for each patient related to toxicities as outlined by the NCI. For Sinusoidal obstructive syndrome, graft failure and posterior reversible encephalopathy syndrome only ICD 10 code were reported.

Clinical characteristics, demographics, procedures and medication of patients were presented using frequency and percentages for categorical variables with a Chi-square p-value (comparisons by ICU admission and Mortality). Univariate and multivariate logistic regression was performed with 'discharge mortality' and 'ICU admission' as primary outcomes. P-value of less than 0.05 or absence of 1 in the 95% confidence intervals was considered statistically significant. All statistical analyses were performed using SAS software, version 9.4 (SAS Institute, Cary, NC) and R software, version 4.0.0.

Results

A total of 13,538 patients met primary inclusion criteria of HSCT. Of these 6,938 transplants (51.2%) were performed to treat a malignant condition. 95.4% of these transplants were allogeneic and most of them performed within 2011 to 2019 (63.4%). Adolescents and Young adults accounted for 18.3% of patients and 8% of all HSCT patients passed away. The most common conditioning regimen reported was Busulfan and Cyclophosphamide (21.04%) and the most used GVHD prophylaxis was Methotrexate and Tacrolimus (21.1%). Common complications reported were acute kidney injury (14%), respiratory failure (12.8%) and acute GVHD (10%). From the patients that developed respiratory failure 90.5% were in the ICU, 80.9% required Mechanical ventilation and 49.6% died. 239 patients developed sinusoidal obstructive syndrome with 67.4% requiring ICU and 20.5% mortality. Defibrotide was used in 60.3% of these patients.

Table 1 and 2 describe our findings and statistically significant results for ICU admission and discharge mortality. Logistic regression and multivariate analysis showed increased ICU admission and discharge mortality in AYA patients (OR 1.36, CI 1.20-1.53, p<.0001 and OR 1.29, CI 1.03-1.64, p<0.03, respectively). From 2009 to 2019 there is an increased OR for ICU admission post HSCT but significant decreased in discharge mortality. Mechanical ventilation was the strongest predictor for ICU admission and discharge mortality (OR 44.81, CI = 37.19-53.99, p<.0001 and OR 31.23, CI = 23.57 – 41.38, p<.0001, respectively), followed by dialysis (OR 5.74, CI = 3.98-8.27, p<.0001 and OR 5.82, CI = 4.62-7.32, p<.0001). Patients diagnosed with sinusoidal obstructive syndrome had 3.2 times OR for ICU (CI = 2.29-4.57, p<.0001) but decreased OR for mortality (OR 0.62, CI 0.39-0.98, p=0.038). SCID and Mucopolysaccharidosis patients had increased OR for ICU admission but not for discharge mortality.

Conclusion

To our knowledge this is the largest multicenter database analysis describing acute non-infectious complications of pediatric HSCT. Survival of HSCT patients that developed SOS have improved since 2016 which may be reflecting the introduction of Defibrotide. Mechanical ventilation was the strongest predictor for mortality with almost 30 times increased in odds ratio. Mucopolysaccharidosis and SCID showed increased need for ICU care but decreased mortality suggesting improvement in intensive care unit management. Prospective studies are needed to better describe outcomes of HSCT patients as well as areas of possible improvement to increase overall survival.