1.
Nomogram for Predicting Early Mortality after Umbilical Cord Blood Transplantation in Children with Inborn Errors of Immunity
Wang, P., Liu, C., Wei, Z., Jiang, W., Sun, H., Wang, Y., Hou, J., Sun, J., Huang, Y., Wang, H., et al
Journal of clinical immunology. 2023
Abstract
PURPOSE Pediatric patients with inborn errors of immunity (IEI) undergoing umbilical cord blood transplantation (UCBT) are at risk of early mortality. Our aim was to develop and validate a prediction model for early mortality after UCBT in pediatric IEI patients based on pretransplant factors. METHODS Data from 230 pediatric IEI patients who received their first UCBT between 2014 and 2021 at a single center were analyzed retrospectively. Data from 2014-2019 and 2020-2021 were used as training and validation sets, respectively. The primary outcome of interest was early mortality. Machine learning algorithms were used to identify risk factors associated with early mortality and to build predictive models. The model with the best performance was visualized using a nomogram. Discriminative ability was measured using the area under the curve (AUC) and decision curve analysis. RESULTS Fifty days was determined as the cutoff for distinguishing early mortality in pediatric IEI patients undergoing UCBT. Of the 230 patients, 43 (18.7%) suffered early mortality. Multivariate logistic regression with pretransplant albumin, CD4 (absolute count), elevated C-reactive protein, and medical history of sepsis showed good discriminant AUC values of 0.7385 (95% CI, 0.5824-0.8945) and 0.827 (95% CI, 0.7409-0.9132) in predicting early mortality in the validation and training sets, respectively. The sensitivity and specificity were 0.5385 and 0.8154 for validation and 0.7667 and 0.7705 for training, respectively. The final model yielded net benefits across a reasonable range of risk thresholds. CONCLUSION The developed nomogram can predict early mortality in pediatric IEI patients undergoing UCBT.
2.
Financial hardship in childhood cancer survivors treated with hematopoietic cell transplant: A report from the Childhood Cancer Survivor Study
Buchbinder, D., Bhatt, N. S., Wang, H., Yasui, Y., Armenian, S., Bhatia, S., Chow, E. J., Huang, I. C., Kirchoff, A. C., Leisenring, W., et al
Transplantation and cellular therapy. 2023
Abstract
BACKGROUND Long-term survivors of childhood cancer are at risk for financial hardship. However, it is not known if HCT leads to an incremental change in financial hardship for survivors who received it vs. those who did not. We examined financial outcomes among adult survivors of childhood cancer who had undergone HCT. METHODS Using a cross-sectional survey in the Childhood Cancer Survivor Study population between 2017-2019, self-reported financial hardship was compared between survivors who received HCT, survivors treated without HCT ("non-HCT"), and siblings and categorized into 3 domains (material hardship/financial sacrifices, behavioral, and psychological hardship). The standardized score of each domain of financial hardship was calculated by adding the item responses and dividing by the standard deviation among siblings. Multivariable linear and logistic regression evaluated associations between socio-demographics, cancer diagnosis, post-treatment complications and financial hardship among survivors. RESULTS Mean adjusted score for each hardship domain among HCT survivors (n=133) was not significantly different from non-HCT survivors (n=2711): material hardship/financial sacrifices (mean difference 0.18, 95% confidence interval [CI] [-0.05, 0.41]), behavioral hardship (0.07, [-0.18, 0.32]), psychological hardship (0.19, [-0.04, 0.42]). Within specific items, a higher proportion of survivors treated with HCT reported greater financial hardship compared to non-HCT survivors. HCT survivors also had significantly higher mean domain scores compared to sibling controls (n=1027) in all domains. Household income and chronic health conditions, but not HCT, were associated with financial hardship among all survivors. CONCLUSIONS Adult survivors of childhood cancer treated with HCT do not report greater overall financial hardship compared to non-HCT survivors; but greater overall financial hardship compared to sibling controls. Surveillance and intervention may be necessary for all survivors regardless of HCT status.
3.
Population Pharmacokinetics of Clofarabine as Part of Pre-Transplant Conditioning in Pediatric Subjects Prior to Hematopoietic Cell Transplantation (HCT)
Wang, H., Jones, A. K., Dvorak, C. C., Huang, L., Orchard, P., Ivaturi, V., Long-Boyle, J.
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2019
Abstract
The primary objective of this work was to characterize the pharmacokinetics (PK) of systemic clofarabine (clo-fara) in pediatric allogeneic hematopoietic cell transplantation (HCT) recipients receiving either nucleoside monotherapy or a dual nucleoside analogue preparative regimen. Fifty-one children (median age 4.9 years, range 0.25-14.9) undergoing allogeneic HCT for a variety of malignant and nonmalignant disorders underwent PK assessments. Plasma samples were collected over the 4-5 days of clofarabine treatment and quantified for clo-fara, using a validated liquid chromatography/tandem mass spectrometry assay. Nonlinear mixed effects modeling was used to develop the population PK model, including identification of covariates that influenced drug disposition. In agreement with previously published models, a two-compartment PK model with first-order elimination best described the PK of clo-fara. Final parameter estimates for clo-fara were consistent with previous reports and were as follows: clearance (CL), 23 L/h/15kg, volume of the central compartment, 42 L/15kg, volume of peripheral compartment, 47 L/15kg, and intercompartmental CL, 9.8 L/h/15kg. Unexplained variability was acceptable at 33% and the additive residual error (reflective of the assay) was estimated to be 0.36 ng/mL. Patient-specific factors significantly impacting clo-fara CL included actual body weight and age. The covariate model was able to estimate clo-fara CL with good precision in children spanning a wide range of ages from infancy to early adulthood and demonstrates the need for variable dosing in children of different ages. For example, the dose required for a 6-month and 1-year old was approximately 43% and 17% lower than the 40 mg/m(2) typical dose to achieve the median AUC0-24 (1.04mg*hr/L) in the studied population. Despite the known renal elimination of clo-fara, no significant clinical parameters for renal function were retained in the final model (p>0.05). Co-administration of fludarabine with clofarabine did not alter the CL of clo-fara (p>0.05). These results will help to inform individualized dosing strategies for clofarabine to improve clinical outcomes and limit drug-related adverse events in children undergoing HCT.