Parents' experiences of pediatric hematopoietic stem cell transplantation: A systematic review and meta-synthesis.

Osteochondroma after Hematopoietic Stem Cell Transplantation in Childhood. An Italian Study on Behalf of the AIEOP-HSCT Group

Pediatric hematopoietic stem cell transplantation (HCT) is an intensive medical procedure that places substantial financial and logistical burdens on families and is associated with significant health risks, such as graft-versus-host disease (GVHD), and infections. The influence of the social determinants of health (SDoH) on outcomes following pediatric HCT is understudied. This study aimed to examine whether SDoH predicts outcomes following pediatric HCT. Data were collected from 84 children who received HCT (Mage =5.8years, SD=3.7) and their primary caregiver. Detailed demographic information was collected from caregivers at baseline, and child health information was extracted from the electronic medical records. Multivariate logistic regression was used to examine the association between SDoH and health outcomes within a 24-month period following pediatric HCT. After controlling for malignancy as reason for transplant and donor type, lower family income predicted the incidence of chronic GVHD. Neighborhood deprivation, total family income, public health insurance, caregiver relationship status, caregiver educational attainment, and perceived family financial difficulties did not predict acute GVHD or the number of infections. Total family income is a simple family indicator of SDoH that predicts chronic GVHD after pediatric allogeneic HCT. These findings provide further support for the importance of screening of child and family SDoH risks to ensure that fundamental needs can be met to mitigate potential health disparities for up to 2years following pediatric HCT.

Data defining the clinical course of COVID19 infection in HSCT recipients are limited. We assessed the impact of COVID19 on paediatric HSCT recipients in the UK between February and June 2020. Nine patients developed COVID 19 proven infection at a median time of 62 days post-transplant. Presenting symptoms were mostly fevers and cough. One case had a severe course, requiring non-invasive ventilation and receiving dexamethasone, tocilizumab, remdesivir. No patients died from COVID19. Two patients developed significant complications following COVID19 disease. Our data describe a relative mild infection course in HSCT recipients but highlight potential infectious triggered complications.

Prognostic impact of donor KIR genotypes on clinical outcomes in pediatric allogeneic hematopoietic stem cell transplantation

Background and Aims Chronic kidney disease (CKD) is an important sequela of hematopoietic stem cell transplantation (HSCT), but data regarding CKD after pediatric HSCT are limited. Method In this single center cohort study, we evaluated eGFR dynamics, proteinuria and hypertension in the first decade after HSCT and assessed risk factors for chronic kidney disease in 216 pediatric long term HSCT survivors, transplanted between 2002 and 2012. Results The eGFR decreased from median 148 to 116 ml/min/1.73m2 between pre-HSCT and ten years after HSCT. CKD, defined as an eGFR <90 ml/min/1.73m2 and/or proteinuria (KDIGO stage ≥G2 or ≥A2) occurred in 21% of patients. In multivariate analysis, hematological malignancy as HSCT indication (HR 5.5, 95% CI 1.2-25) and cytomegalovirus reactivation (HR 2.4, 95% CI 1.1-5.4) were independent risk factors for CKD. One third of patients with CKD had both an eGFR <90 ml/min/1.73m2 as well as proteinuria, one third had isolated eGFR reduction and one third only had proteinuria. Hypertension was observed in 27% of patients with CKD compared to 4.4% of patients without CKD. Tubular proteinuria was present in 7% of the subgroup of patients (n=71) in which β2-microglobulinuria was measured. Conclusion In conclusion, a significant proportion of pediatric HSCT recipients developed chronic kidney disease within ten years after HSCT. Our data stress the importance of structural long term monitoring of eGFR, urine and blood pressure after HSCT to identify patients with beginning CKD who could benefit most from nephroprotective interventions.

Metabolic Syndrome in Male Survivors of Pediatric Allogeneic Hematopoietic Stem Cell Transplantation: Impact of Total Body Irradiation, Low-Grade Inflammation, and Hypogonadism

Chronic kidney disease (CKD) is an important sequela of hematopoietic stem cell transplantation (HSCT), but data regarding CKD after pediatric HSCT are limited. In this single center cohort study, we evaluated the estimated glomerular filtration rate (eGFR) dynamics, proteinuria and hypertension in the first decade after HSCT and assessed risk factors for CKD in 216 pediatric HSCT survivors, transplanted 2002-2012. The eGFR decreased from a median of 148 to 116 ml/min/1.73 m2 between pre-HSCT to ten years post-HSCT. CKD (KDIGO stages G2 or A2 or more; eGFR under 90 ml/min/1.73m2 and/or albuminuria) occurred in 17% of patients. In multivariate analysis, severe prolonged stage 2 or more acute kidney injury (AKI), with an eGFR under 60ml/min/1.73m2 and duration of 28 days or more, was the main risk factor for CKD (hazard ratio 9.5, 95% confidence interval 3.4-27). Stage 2 or more AKI with an eGFR of 60ml/min/1.73m2 or more and KDIGO stage 2 or more AKI with eGFR under 60ml/min/1.73m2 but recovery within 28 days were not associated with CKD. Furthermore, hematological malignancy as HSCT indication was an independent risk factor for CKD. One third of patients had both CKD criteria, one third had isolated eGFR reduction and one third only had albuminuria. Hypertension occurred in 27% of patients with CKD compared to 4.4% of patients without. Tubular proteinuria was present in 7% of a subgroup of 71 patients with available β2-microglobulinuria. Thus, a significant proportion of pediatric HSCT recipients developed CKD within ten years. Our data stress the importance of structural long-term monitoring of eGFR, urine and blood pressure after HSCT to identify patients with incipient CKD who can benefit from nephroprotective interventions.

JAK1/2 Inhibition As a Salvage Therapy for Steroid Refractory Acute and Chronic Graft Versus Host Disease in Pediatric Allogeneic Hematopoietic Stem Cell Transplant Recipients

Hematopoietic stem cell transplantation (HCT) is a potentially curative treatment for children with hematological or immunological disorders. However, treatment-related morbidity and mortality remain concerning. Various comorbidity indices are currently used to assess the risk of complications following pediatric HCT. We compared four comorbidity indices to determine which can most accurately estimate the risk of morbidity and mortality in pediatric nonmalignant HCT. We analyzed 308 pediatric allogeneic nonmalignant HCTs performed between January 2010 and December 2022. Four indices were evaluated: hematopoietic stem cell transplantation-specific comorbidity index (HCT-CI), youth nonmalignant hematopoietic stem cell transplantation comorbidity index (ynHCT-CI), simplified ynHCT-CI, and simplified comorbidity index (SCI). The primary outcome was overall survival (OS). The secondary outcome was graft-versus-host disease (GvHD)-free event-free survival (EFS), defined as acute GvHD Grade 3 or 4, extensive chronic GvHD, retransplantation, or death. The area under the receiver operator characteristic curve (AUC) was calculated per index and outcome at 100 days, 1 year, and 2 years post-HCT. For OS, AUC values ranged from 0.611 to 0.755. The simplified ynHCT-CI and ynHCT-CI generally had superior discriminative abilities for OS, although no significant difference was found. For EFS, AUC values were between 0.539 and 0.632. The ynHCT-CI performed best for EFS, with AUC values of the simplified ynHCT-CI marginally lower. The ynHCT-CI significantly outperformed the HCT-CI at 100 days post transplantation (p=0.045). The ynHCT-CI most accurately predicted outcomes after pediatric nonmalignant HCT. We propose the use of ynHCT-CI in future clinical management guidelines in this cohort.

Male Gonadal Function after Allogeneic Hematopoietic Stem Cell Transplantation in Childhood: A Cross-Sectional, Population-Based Study.

193: Osteonecrosis in Pediatric Hematopoietic Stem Cell Transplantation

Background Varicella-zoster virus (VZV) infection is known to occur in 13-55% of patients within the first year after hematopoietic stem cell transplant (HSCT). The dynamics of recovery of VZV-specific T cell- mediated immunity (CMI) and its role for prevention and control of VZV reactivation are rarely reported in pediatric allogenic HSCT recipients. Methods From April 2019 to February 2020, subjects aged younger than 19 years who underwent allogenic HSCT with at least 1 year of follow up at Asan Medical Center Children`s Hospital were prospectively enrolled. All of them underwent VZV-specific enzyme-linked immune absorbent spot (ELISPOT) assays just before HSCT and then at 1, 3 months following HSCT. Extension study, which measures VZV-specific CMI before and after VZV vaccination at 24 months post-HSCT, is currently underway. Results A total of 32 HSCT recipients with a median age of 11years were enrolled. 37.5% underwent haploidentical HSCT and VZV R+ were in 78.1%. Antiviral prophylaxis was applied to all HSCT recipients, of which 65.6% were applied up to 365 days after HSCT. During this study period, only 1 patient (3.1%) experienced herpes zoster at 23 months following HSCT, whose VZV-specific ELISPOT assay showed 0, 1, and 0 spot-forming cells (SFC)/2.0x105 cells before HSCT, 1 and 3 months following HSCT, respectively. The presence of VZV-specific CMI ≥ 1 SFC/ 2.0 × 105 cells was observed in 62.5 % before HSCT, 65.6 % at 1 month, 59.4 % at 3 months, and 70% at 24 months after HSCT, respectively. However, only 18.8 % ,12.5 % and 21.9 % recovered VZV-specific CMI with ≥ 5 SFC/ 2.0 × 105 cells at 1, 3 and 24 months following HSCT. Meanwhile, all the 4 recipients who got the 1st VZV vaccination at 24 months following HSCT showed recovery of VZV-specific CMI with ≥ 5 SFC/ 2.0 × 105 cell. Recovery of VZV-specific CMI after HSCT was not associated with VZV serostatus, chickenpox history, type of HSCT, conditioning regimens, and GVHD. Conclusion Only a few pediatric allogenic HSCT recipients recovered VZV-specific CMI with ≥ 5 SFC/ 2.0 × 105 cell up to 2 years following HSCT. In addition, the association between VZV-specific CMI and VZV reactivation could not be analyzed because no one experienced VZV reactivation within 1 year after HSCT. More long-term large-scale multicenter study is mandatory to supplement these parts. Disclosures All Authors: No reported disclosures.

Systemic lupus erythematosus in a 15-year-old with graft-versus-host disease following liver transplant and unexpected full hematopoietic engraftment

Delayed Platelet Engraftment and Early Increased Creatinine after Stem Cell Transplant Predicts Sustained Remission in Pediatric Leukemia.

The impact of pediatric hematopoietic stem cell transplant (HCT) on family functioning varies, but little is known about how the timing of HCT in children's treatment course contributes to this variability. This study examines how preexisting child, sibling, and family problems, the length of time between diagnosis to HCT, and children's age at HCT are associated with family and caregiver functioning. Caregivers (n=140) of children (≤18 years old) scheduled to undergo their first HCT completed the Psychological Assessment Tool-HCT and the Impact on Family Scale. Treatment information was extracted from electronic medical records. A bootstrapped multivariate path analysis was used to test the hypotheses. More preexisting family problems related to greater caregiver perceived negative impact of their child's HCT across family and caregiver functioning domains. Less time between diagnosis and HCT was associated with greater caregiver personal strain, particularly for those with younger children undergoing HCT. Younger child age at HCT was also associated with a larger negative impact on family social functioning. Families with preexisting problems are the most at-risk for experiencing negative impacts related to their child's HCT. The timing of a child's HCT within their treatment course and the child's age during HCT may impact families' social functioning and caregiver adjustment. Screening families for preexisting family problems, particularly for families with young children or who are abruptly learning of their child's need for an HCT, may assist providers in identifying families who would benefit from earlier or more intensive psychosocial support.