Population Pharmacokinetic Analysis of N‐acetylcysteine in Pediatric Patients with Inherited Metabolic Disorders Undergoing Hematopoietic Stem Cell Transplant

2021 ◽  
Author(s):  
Siddhee A Sahasrabudhe ◽  
Reena V Kartha ◽  
Michelle Ng ◽  
Lisa M Basso ◽  
Usha Mishra ◽  
...  
Keyword(s):  
Metabolic Disorders ◽  
Hematopoietic Stem Cell Transplant ◽  
Pediatric Patients ◽  
Stem Cell Transplant ◽  
Population Pharmacokinetic Analysis ◽  
Pharmacokinetic Analysis ◽  
Population Pharmacokinetic ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Inherited Metabolic Disorders

scholarly journals Morbidity, Mortality, and Healthcare Utilization in a National Cohort of Pediatric Patients with Hemophagocytic Lymphohistiocytosis Who Received Hematopoietic Stem Cell Transplant

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2183-2183
Author(s):  
Archana Ramgopal ◽  
Meghan McCormick ◽  
Ram Kalpatthi ◽  
Louis Rapkin ◽  
James Zullo ◽  
...  
Keyword(s):  
Stem Cell ◽  
Resource Utilization ◽  
Hemophagocytic Lymphohistiocytosis ◽  
Hematopoietic Stem Cell Transplant ◽  
Pediatric Patients ◽  
Stem Cell Transplant ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Elapsed Time ◽  
Over Time

Background Hemophagocytic lymphohistiocytosis (HLH) is a severe life threatening hyper-inflammatory syndrome of abnormal immune activation and dysregulation if untreated. The 5-year probability of survival (pSu) obtained from HLH registries and treatment protocols HLH-94 and HLH-2004 ranges from 21%-64%, with improved 5-year pSu of up to 70% following hematopoietic stem cell transplant (HSCT) (Arico et al., Trottestam et al., Bergsten et al.). Despite significant advances in the management of HLH over time, survival remains low and the extent of disease morbidity and healthcare utilization is poorly characterized. In this study, we sought to investigate morbidity, mortality, and the healthcare burden in children and adolescents with HLH who underwent HSCT. Methods Using the Pediatric Health Information System (PHIS) database, we identified patients under the age of 21 years admitted between 01/01/2004 and 09/30/2018 with a primary or secondary ICD-9 or ICD-10 diagnosis codes for HLH, as well as concurrent medication charges for both dexamethasone and etoposide in the same encounter. We then identified the patients who underwent HSCT to further analyze them. We abstracted data on demographics, hospitalizations, HSCT related complications, mortality, resource utilization and costs. Results were summarized using descriptive statistics. Time to HSCT was calculated as elapsed time from the admission date of the initial encounter to the date of the encounter in which there was a procedure code for HSCT. Time to mortality event was calculated as elapsed time from the admission date of the initial encounter to the discharge date of the encounter in which mortality occurred. The PHIS database provides an encrypted patient medical record number; thus, we were able to follow patients over time. This allowed for a better visualization of the patient's hospitalizations trend over 14 years. Results A total of 493 patients met inclusion criteria for HLH during the study period from 52 children's hospitals. The majority of patients (n = 284, 58%) were less than 5 years of age. Of these, 136 patients (28%) underwent HSCT with 155 hospital encounters, including readmissions. The median age at the time HSCT was 2 years (IQR; 0-9 years) and there were 82 males (60%). The median time to HSCT was 126 days (IQR: 75-193 days) and the average length of stay for the initial HSCT hospitalization was 61.1 days. Median initial HSCT hospitalization cost was $463,630 (IQR; 230,795 - 558,533). ICU care was required for 71 (46%) of patients. Overall, 91 (67%) patients developed transplant-related complications, which included infections, sinusoidal obstruction syndrome or graft versus host disease (Table 1). Mortality after HSCT was 22% (n=30) with an increased mortality observed with advanced age at the time of HSCT (Figure 1). The median time to death after the initial HSCT admission was 65 days (IQR; 56-94 days). Conclusion This is a large in-patient cohort of pediatric patients with HLH who underwent HSCT in the US. We observed an improved overall mortality after HSCT in this population compared to previous studies. However, morbidity (particularly from infections) and heath care resource utilization remain high. This stresses the importance of novel therapeutic approaches to improve not only patient survival but also long-term quality of life. Planned future analysis of this database will be aimed at assessing treatment variability; morbidity and mortality by treatment regimen, time to HSCT, and HSCT preparative regimen; and risk factors associated with mortality in pediatric patients with HLH who do and do not undergo HSCT. Disclosures No relevant conflicts of interest to declare.

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