The value of using patient-reported outcomes for health screening during long-term follow-up after paediatric stem cell transplantation for nonmalignant diseases.

INTRODUCTION: The assessment of using patient-reported outcomes (PROs) within comprehensive care follow-up programmes, specifically focused on health screening, remains largely unexplored. PROs were implemented in our late effects and comprehensive care programme after paediatric hematopoietic stem cell transplantation (HSCT) for nonmalignant diseases. The programme focuses solely on screening of physical and mental health and on discussing PROs during the consultation. METHODS: The primary method of this study was semistructured interviews to explore the perspective of both patients and healthcare providers' (HCP) on the use of PROs, which were thematically analyzed. Additionally, an explorative quantitative approach with patient-reported experience measures (PREMS) was used, with a pretest-posttest design, to assess whether the use of PROs was accompanied by more patient-centred care. RESULTS: From the patient-interviews (N = 15) four themes were extracted: use of PROs (1) help to discuss topics; (2) make the patients feel understood; (3) create a moment of self-reflection; and (4) make consultations more efficient. Pre- and postimplementation analysis of PREMs (N = 40) did not show significant differences in terms of patient-centeredness. CONCLUSION: Our results demonstrate the added value of integrating PROs for health screening purposes within the long-term follow-up programme after paediatric HSCT, as perceived by both patient and HCP. With the active use of PROs, patients are stimulated to consciously assess their health status. PATIENT CONTRIBUTION: This study included patients as participants. Caregivers were approached if patients were below a certain age. Additionally, preliminary results were shared with all patients (including nonparticipants) during a patient conference day.

Long-term parental distress after pediatric hematopoietic stem cell transplantation for nonmalignant diseases.

BACKGROUND: Survival rates have continued to increase for pediatric hematopoietic stem cell transplantation (HSCT) for nonmalignant diseases. Despite the crucial role of caregivers in this high-intensity treatment, knowledge about long-term parental impact is lacking. PROCEDURE: This cross-sectional study assessed parental distress and everyday problems in parents of patients 2 years and older after pediatric HSCT for a nonmalignant disease using Distress Thermometer for Parents (DT-P), and compared outcomes to matched Dutch parents of healthy children and Dutch parents of children with a chronic condition (CC). RESULTS: Median follow-up was 5.3 years (interquartile range [IQR]: 2.9-8.6). Underlying diseases were inborn errors of immunity (N = 30), hemoglobinopathies (N = 13), and bone marrow failure (N = 27). Mothers of pediatric HSCT recipients (N = 70) reported comparable overall distress levels to mothers of healthy children, but experienced more distress related to parenting problems, specifically managing their child's emotions, discussing disease consequences, and fostering independence. Fathers of HSCT recipients (N = 45) reported higher overall distress levels and had more emotional distress compared to fathers of healthy children. CONCLUSIONS: Overall, parental distress and everyday problems of parents of HSCT recipients are comparable to those of parents of children with CC. However, there is ongoing parental burden, both emotional and in parenting, long-term after HSCT compared to parents of healthy children, and the type of burden differs between mothers and fathers. These results indicate that individualized parental supportive care should not remain restricted to the acute hospitalization phase, but also be actively offered during long-term follow-up after pediatric HSCT.

Effect of Busulfan and Treosulfan on Gonadal Function after Allogeneic Stem Cell Transplantation in Children and Adolescents with Nonmalignant Diseases Is Not Exposure-Dependent.

With an increasing number of young patients surviving into adulthood after hematopoietic stem cell transplantation (HSCT), gonadal dysfunction becomes an important late effect with significant impact on quality of life. In this retrospective study, we evaluated the exposure of busulfan (Bu) and treosulfan (Treo) in relation to gonadal function in pediatric patients who underwent HSCT for a nonmalignant disease between 1997 and 2018. In the Bu group, 56 patients could be evaluated, and gonadal dysfunction was found in 35 (63%). Lower Bu exposure (ie, cumulative area under the curve [AUC] <70 mg*h/L) was not associated with a reduced risk of gonadal dysfunction (odds ratio [OR], .92; 95% confidence interval [CI], .25 to 3.49; P = .90). In the Treo cohort, 32 patients were evaluable and gonadal insufficiency occurred in 9 patients (28%). Lower Treo exposure (AUC <1750 mg*h/L on day 1) was not associated with a reduced risk of gonadal dysfunction (OR, 1.6; 95% CI, .16 to 36.6; P = .71). Our data do not support the premise that reduced-intensity Bu-based conditioning reduces the risk for gonadal toxicity, and it is unlikely that therapeutic drug monitoring-based reduced treosulfan exposure will further limit the risk of gonadal dysfunction.

Late Effects in Pediatric Allogeneic Hematopoietic Stem Cell Transplantation for Nonmalignant Diseases: Proxy- and Patient-Reported Outcomes.

Survival rates in pediatric hematopoietic stem cell transplantation (HSCT) for nonmalignant diseases have improved due to advances in conditioning regimens, donor selection, and prophylaxis and treatment of infections and graft-versus-host disease. Insight into the long-term patient-reported outcomes (PROs) after pediatric HSCT for nonmalignant disease is lacking but essential for optimal shared decision making, counseling, and quality of care. The purpose of this research was to determine long-term patient-reported outcomes in allogeneic pediatric HSCT for nonmalignant diseases and to compare these results with Dutch reference data. This single-center cohort study evaluated PROs (PedsQL 4.0, PROMIS item banks), self- or proxy-reported, among patients at ≥2 years after pediatric allogeneic HSCT for nonmalignant disease. Mean scores were compared with those of the Dutch general population. Of 171 eligible patients, 119 participated, for a 70% response rate. The median patient age was 15.8 years (range, 2 to 49 years), and the median duration of follow-up was 8.7 years (range, 2 to 34 years). Indications for HSCT included inborn errors of immunity (n = 41), hemoglobinopathies (n = 37), and bone marrow failure (n = 41). Compared with reference data, significantly lower scores were found in adolescents (age 13 to 17 years) on the Total, Physical Health, and School Functioning PedsQL subscales. Significantly more Sleep Disturbance was reported in children (age 8 to 18 years). On the other hand, significantly better scores were seen on PROMIS Fatigue (age 5 to 7 years) and Pain Interference (age 8 to 18 years) and, in adults (age 19 to 30 years), on Depressive Symptoms and Sleep Disturbance. This study showed better or comparable very long-term PROs in patients after pediatric HSCT for nonmalignant diseases compared with the reference population. Children and adolescents seem to be the most affected, indicating the need for supportive care to prevent impaired quality of life and, more importantly, to amplify their long-term well-being.

Exploring the long-term psychosocial impact of paediatric haematopoietic stem cell transplantation for nonmalignant diseases.

INTRODUCTION: An understanding of the long-term psychosocial impact of paediatric haematopoietic stem cell transplantation (HSCT) for nonmalignant diseases is needed to optimize pre-HSCT counselling, supportive care and long-term follow-up programmes after HSCT for this group of patients and caregivers. METHODS: This qualitative study included 14 patients who underwent transplantation for a nonmalignant disease during childhood. In-depth interviews were held online to explore patients' perspectives on the long-term psychosocial impact of HSCT on their lives. The results were analysed based on the Grounded Theory approach. RESULTS: Patients' median age at the time of the interview was 19 years (range: 14-49), and the median years after HSCT was 12 years (range: 3-33). Four main themes were identified: (1) doing okay, (2) experiencing persistent involvement with healthcare services, (3) influence on relationships with loved ones and (4) impact on the patient's life course. Subthemes extracted were doing okay, feeling of being cured, health limitations, sense of vulnerability, ongoing connection to the hospital, acceptance, friendship, family relations, development of own identity, not taking life for granted, social development, impact on (school) career and thinking about the future. CONCLUSIONS: Patients reported active coping strategies and resilience after this high-impact treatment. The data highlight the need for patient-adjusted supportive care, indicating more need for supportive care in the long-term outpatient clinic. PATIENT CONTRIBUTION: This study included patients as participants. Caregivers were approached if patients were below a certain age. Additionally, preliminary results were presented during a patient conference day.

Chronic kidney disease ten years after pediatric allogeneic hematopoietic stem cell transplantation.

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 ß2-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.