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An infant with neonatal Marfan syndrome is described who presented with arachnodactyly, distinctive dysmorphic features and prolapse of both atrioventricular valves and dilatation of both the aortic and pulmonary root. She died in cardiac failure shortly after pacemaker implantation, due to dysrhythmia and severe mitral insufficiency. At autopsy, apart from myxomatous changes of the valves and dilated aortic and pulmonary roots, an aneurysm of the sinus of Valsalva of the pulmonary valve and abnormal myxomatous connective tissue surrounding the AV node were also found. Molecular genetic studies showed a point mutation in the fibrillin 1 gene that creates a new N-glycosylation site, which has been described once before. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to assess late effects of cytotoxic therapy with hematopoietic stem cell transplantation (HCT) on dental development in survivors of childhood cancer.Materials and Methods: Forty children who underwent allogeneic HCT for a variety of hematological malignancies were evaluated at a minimum of 2 years after transplantation. We obtained information on oral symptoms, exposed panoramic radiographs (PRG), and performed an oral examination. PRGs were scored for agenesis and root and/or crown abnormalities. The root-crown ratio was calculated, and dental age was assessed using Demirjian' s method.Main Results: The studied group showed a significantly higher prevalence of tooth agenesis compared to normative data for first and second premolars in both the maxilla and mandible, as well as the second molars in the mandible (all p values <0.001). Children who were <3 years old at the time of cancer treatment had significantly more missing teeth than older children, F(2,37) = 7.58, p < 0.002. Root-crown ratios were lower in the study sample than those from normative data. In addition, the mean dental age was higher (as a result of earlier apical root closure) than the mean chronological age, t(28) = 2.47, p < 0.020.Conclusions: Nearly all children examined had dental development disturbances, including agenesis, short roots, and arrested root development. An oral/dental evaluation and preventative oral supportive care regimens should be part of programs monitoring late effects in long-term survivors of childhood cancer. [ABSTRACT FROM AUTHOR]

To investigate the health-related quality of life (HRQOL) of Dutch adult childhood cancer survivors (CCS) and to identify risk factors of impaired HRQOL. Adult CCS (age >18, diagnosed <18, ≥5 years since diagnosis) from the Dutch LATER registry completed the Medical Outcome Study Short Form 36 (SF-36) to measure HRQOL and provided sociodemographic characteristics. Age-adjusted mean SF-36 scale scores of CCS were compared to the Dutch general population for men and women separately using t-tests, with effect size d. Multivariate logistic regression models were built to identify sociodemographic and cancer-related risk factors for impaired physical and mental HRQOL. Both male and female CCS (N = 2301, mean age = 35.4 years, 49.6% female) reported significantly (p ≤.005) worse HRQOL than the general population on almost all scales of the SF-36 (−.11 ≤ d ≤ −.56). Largest differences were found on vitality and general health perceptions. Significant risk factors (p ≤.05) for impaired physical HRQOL were female sex, older age at diagnosis, not having a partner, low educational attainment, disease recurrence and exposure to radiotherapy, specifically to lower extremity radiation. Odds ratios (ORs) ranged from 1.6 to 3.7. Significant risk factors for impaired mental HRQOL were age 26–35 years, male sex, not having a partner and low educational attainment. ORs ranged from 1.3 to 2.0. Adult CCS had worse HRQOL than the general population. CCS most at risk were those with low educational attainment and without a partner. Adult CCS could benefit from routine surveillance of their HRQOL. Special attention for CCS' vitality and health perceptions and beliefs is warranted. • The first nationwide cohort study of health-related quality of life (HRQOL) in Dutch adult childhood cancer survivors (CCS) (N = 2301). • Dutch adult CCS reports worse HRQOL than the general population. • Cancer-related risk factors are associated with impaired physical, not mental HRQOL. • Risk factors for impaired physical/mental HRQOL are low education and having no partner. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate pregnancy rates, time to pregnancy (TTP) and obstetric outcomes in female childhood cancer survivors (CCSs) and to identify specific diagnosis- and treatment-related factors associated with these outcomes. Methods: The study is part of the DCOG LATER-VEVO study, a nationwide multicenter cohort study evaluating fertility among long-term Dutch female CCSs. Data were collected by questionnaire. The current study included 1095 CCSs and 812 controls, consisting of sisters of CCSs and a random sample of women from the general population. Results: Among the subgroup of women who ever had the desire to become pregnant, the chance of becoming pregnant was significantly lower for CCSs than controls (OR 0.5, 95%CI 0.4–0.8). Moreover, TTP was 1.1 times longer for CCSs compared to controls (p = 0.09) and was significantly longer in survivors of CNS and renal tumours. Overall, no differences were found between CCSs and controls regarding the probability of ever having had a miscarriage, still birth, or induced abortion. However, CCSs had a significantly increased risk of delivering preterm (OR 2.2, 95%CI 1.3–3.7) and delivering via caesarean section (OR 1.8, 95%CI 1.2–2.6). Treatment with lower abdominal/pelvic radiotherapy was strongly associated with several adverse obstetric outcomes. Conclusion: CCSs are less likely to have ever been pregnant. Among those who do become pregnant, certain subgroups of CCSs are at increased risk of longer TTP. Moreover, as pregnant CCSs, especially those treated with lower abdominal/pelvic radiotherapy, are more likely to develop various adverse obstetric outcomes, appropriate obstetric care is highly advocated. [ABSTRACT FROM AUTHOR]

Little information is available on the use of appropriate comparison groups for studies investigating late effects of childhood cancer. Two comparison groups in a nationwide study on reproductive function and ovarian reserve in female childhood cancer survivors were recruited (The Dutch Childhood Oncology Group Long-Term Effects After Childhood Cancer Cohort Study). Experiences of this process are reported. Two types of comparison groups were used: sisters of participating survivors and controls from the general population. A total of 352 out of 580 (61%) of the participating survivors who had a sister gave permission to invite them for the study. The participation rate of sisters was much higher than control participants from the general population (74% versus 21%, respectively), whereas considerably more effort was involved in recruiting controls from the general population. Participants in this group were significantly older and more highly educated than sister controls (P < 0.001 for both groups). No significant differences were observed between both types of comparison groups in several fertility-related characteristics, suggesting minimal bias owing to selective participation. Researchers setting up a study to investigate late effects among survivors of childhood cancer should carefully consider the advantages and disadvantages of using various types of comparison groups. [ABSTRACT FROM AUTHOR]

With the aim of assessing parental stress after SCT, 73 parents of children and adolescents who underwent SCT 5 or 10 years ago responded to questionnaires on general distress (General Health Questionnaire (GHQ)), disease-related stress (Pediatric Inventory for Parents-short form (PIP-SF)) and perceptions of child vulnerability (Child Vulnerability Scale (CVS)). General distress scores were comparable with the reference groups, but 40% of the mothers at 5 years after SCT reported increased stress levels as compared with 26% in the community-based reference group. Disease-related stress was comparable with the reference group of parents of children who were just off cancer treatment, 5 years after SCT. At 10 years after SCT, scores were lower than the reference group. Perceived child vulnerability did diminish over time, but remained high in parents of SCT survivors, compared with parents of healthy children: 96% of the parents at 5 years after SCT and 76% of the parents at 10 years after SCT scored above the cutoff point. Perceived vulnerability was found to be a predictor for parental disease-related stress. To conclude, although most parents of SCT survivors are resilient, the majority of parents perceive their child to be much more vulnerable as compared with parents of healthy children. This perception is associated with disease-related stress and may induce overprotective parenting. [ABSTRACT FROM AUTHOR]

Purpose: To explore putative causal relations for chronic fatigue (CF) in childhood cancer survivors (CCS) using structural equation modeling (SEM)., Methods: Interrelationships between factors that were previously associated with CF and their causal relation with CF were investigated using SEM and causal discovery methodology. A bootstrap method was used to ascertain how robust each finding was, presenting the percentage of times that each discovered edge was found in 1000 bootstrap samples as a measure of confidence (with > 50% needed to be confident in a found edge)., Results: 1927 CCS (51.7% male) with a mean age of 35 years (SD 9) participated in the study (23.6% reported CF). Results indicated that sex had a putative causal effect on CF (bootstrap confidence 81%), while CF was causally linked to helplessness, physical activity, pain, BMI, and sleep problems (bootstrap confidence 82%, 78%, 78%, 51%, and 51%, respectively). The relation between CF and depression was found to be two-way (bootstrap confidence 68%), indicating a reciprocal relation or the presence of a latent confounder. The same applied to the relations between CF and anxiety, self-esteem, and social functioning, but this could not be confirmed with high confidence (bootstrap confidence < 50%)., Conclusion: This study provides insight into the complex etiology of CF and could give guidance in the development of appropriate prevention and/or intervention strategies for CF in CCS., Implications for Cancer Survivors: Results show the consequences of having CF and could help to understand the impact it has on daily life., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Anti-thymocyte globulin (ATG) is used in pediatric allogeneic hematopoietic cell transplantation (HCT) to prevent graft-versus-host-disease (GvHD) and graft failure (GF). Poor or delayed T-cell recovery, associated with increased mortality, is the main toxicity of ATG. Model-based precision dosing of ATG (MBD-ATG) minimizes toxicity while maintaining efficacy. We report updated results of the single-arm phase II PARACHUTE trial investigating MBD-ATG, combined with real-world experience with identical MBD-ATG. Consecutive pediatric patients receiving a first T-cell replete HCT for any indication were evaluated. Results were compared to historical patients receiving conventional fixed ATG dosing (FIX-ATG). Primary outcome was overall survival (OS). The MBD-group consisted of 214 patients (58 trial patients, 156 real-world patients); 100 patients received FIX-ATG. MBD-ATG led to superior OS compared to FIX-ATG (hazard ratio [HR] for death 0.56, 95% confidence interval [CI] 0.34-0.93, p=0.026), mainly due to lower treatment related mortality (TRM; HR 0.51, 95% CI 0.29-0.92, p=0.025). Successful T-cell reconstitution (>0·05 × 10⁹ CD4+ T-cells/L twice within 100±3 days after HCT) was improved in MBD-ATG versus FIX-ATG (87%±2% versus 47%±5%, p<0.0001). The improved T-cell reconstitution led to lower TRM (HR 0.19, 95% CI 0.09-0.36, p<0.0001). Incidence of grade 2-4 acute GvHD was comparable, while chronic GvHD (HR 0.35, 95% CI 0.17-0.72, p=0.004) and GF (HR 0.36, 95% CI 0.13-0.97, p=0.044) were both less frequent in MBD-ATG compared to FIX-ATG. MBD-ATG results in improved OS and reduced TRM, while reducing chronic GvHD and GF. This easy-to-implement approach can improve outcomes after pediatric HCT though confirmatory studies are urgently needed., (Copyright © 2025 American Society of Hematology.)

Context/objective: Diabetes mellitus (DM), a possible adverse effect of childhood cancer treatment, is strongly associated with cardiovascular disease and early mortality in adult childhood cancer survivors (CCS). Here, we assess the prevalence and determinants of DM in our nationwide CCS cohort., Design/methods: In this cross-sectional study, the prevalence of DM was assessed in 2,338 CCS, using the Lifelines cohort (n=132,226 adults with no history of cancer) as a reference. DM was defined through serum glucose measurement (fasting glucose ≥7.0mmol/L or non-fasting ≥11.1mmol/L) and/or self-report (previous diagnosis and/or medication use). Multivariable logistic regression models, adjusted for age, sex, and BMI, were used to assess the cohort effect on the presence of DM. Multivariable logistic regression analysis was used to identify determinants of DM in CCS., Results: Survivors (median age 34.7 years, median follow-up time 27.1 years) showed increased odds for hyperglycemia (aOR=2.72, 95%CI=2.06-3.59), previous DM diagnosis (aOR=3.03, 95%CI=2.33-3.95), and anti-diabetic medication use (aOR=2.94, 95%CI=2.17-3.99), compared to the reference cohort. Age (OR=4.32, 95%CI=1.84-10.15, >35 versus 18-35 years), BMI (OR=1.12, 95%CI=1.08-1.16, per point), family history of DM (OR=2.38, 95%CI=1.51-3.76), prior abdominal/pelvic radiotherapy (OR=4.19, 95%CI=2.32-7.55), total body irradiation (OR=14.31, 95%CI=6.98-29.34), hypogonadism (OR=2.40, 95%CI=1.15-4.99), hypertension (OR=1.71, 95%CI=1.06-2.76), and dyslipidemia (OR=3.81, 95%CI=2.15-6.75) were associated with DM in CCS. A significant interaction between age and sex on the development of DM in survivors was identified., Conclusions: The identified three-fold increased risk of DM in CCS, along with the clinically relevant -and some modifiable- determinants, underscores the importance of early risk-based screening and the exploration of lifestyle interventions in this population., (© The Author(s) 2025. Published by Oxford University Press on behalf of the Endocrine Society.)

Background: Treatment for childhood cancer may increase the risk of long-term pulmonary complications and dysfunction. Pulmonary surveillance is recommended after established pulmonary toxic exposures, including bleomycin, busulfan, carmustine (BCNU), lomustine (CCNU), radiotherapy to a field exposing the lungs, and pulmonary surgery. However, the role of cyclophosphamide as a pulmonary toxic agent is debated., Aim: To establish whether cyclophosphamide is associated with late pulmonary dysfunction among survivors of childhood cancer., Methods: In this multicenter Dutch Childhood Cancer Survivor Study (DCCSS)-LATER 2 PULM sub-study, we included 828 survivors with a median follow-up of 26.6 years, treated with cyclophosphamide and/or established pulmonary toxic treatment, or neither. Pulmonary function tests were used to measure the primary outcomes of diffusion impairment (diffusing capacity for carbon monoxide (DLCO) z-score), restriction (total lung capacity (TLC) z-score), and obstruction (forced expiratory volume in the first second/forced vital capacity (FEV1/FVC) z-score). Secondary outcomes comprised chronic cough, recurrent respiratory tract infections, shortness of breath, and supplemental oxygen need., Results: Diffusion and restrictive abnormalities were highly prevalent among those treated with established pulmonary toxic treatment, with cyclophosphamide (41.0 % and 50.4 %, respectively) and without (34.3 % and 41.9 %, respectively), and occurred less frequently in survivors treated with cyclophosphamide only (12.9 % and 7.3 %, respectively) or in survivor controls (9.9 % and 12.4 %, respectively). In multivariable analyses, cyclophosphamide did not have a clinically relevant effect on the primary or secondary outcomes., Conclusions: This study suggests that cyclophosphamide is not associated with clinically relevant pulmonary dysfunction in long-term childhood cancer survivors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

Background: Because the occurrence of metabolic syndrome (MetS) might contribute to childhood cancer survivor's excess risk of cardiovascular disease, the authors assessed the prevalence and determinants of MetS in the Dutch Childhood Cancer Survivor Study (DCCSS-LATER2) cohort., Methods: In total, 2338 adult childhood cancer survivors (CCS) were cross-sectionally assessed for the prevalence of MetS, using the Lifelines cohort (N = 132,226 adults without a history of cancer) as references. The prevalence of MetS was clinically assessed using existing classifications, as well as an alternative method using dual-energy x-ray absorptiometry fat% instead of waist circumference to define abdominal adiposity. Logistic regression models, adjusted for age and sex, were used to investigate the association between the presence of MetS and both cohorts. Demographic, lifestyle, and treatment determinants of MetS were identified through multivariable logistic regression., Results: The survivor cohort (median age, 34.7 years, median follow-up time, 27.1 years) showed increased adjusted odds ratio (aOR) for MetS (modified National Cholesterol Education Program Adult Treatment Panel III criteria), as compared to the reference cohort (aOR, 2.07; 95% confidence interval [CI], 1.85-2.32). Compared to these criteria, the alternative method identified 57 additional survivors with MetS (395 of 2070 [19.1%] vs. 452 of 1960 [23.1%], respectively). Age (odds ratio [OR], 1.07; 95% CI, 1.04-1.10, per year increase), smoking (OR, 1.46; 95% CI, 1.04-2.04), low physical activity (OR, 1.48; 95% CI, 1.05-2.09), abdominal radiotherapy (OR, 2.13; 95% CI, 1.01-4.31; >30 Gy), cranial radiotherapy (OR, 2.89; 95% CI, 1.67-4.96; 1-25 Gy; and OR, 2.44; 95% CI, 1.30-4.47; >25 Gy), total body irradiation (OR, 6.17; 95% CI, 3.20-11.76), and underlying central nervous system tumor (OR, 1.78; 95% CI, 1.21-2.60) were associated with MetS., Conclusion: The high risk of MetS in CCS, combined with several potential modifiable factors, underscores the need for timely identification and intervention strategies to mitigate the long-term cardiovascular risks in CCS., (© 2025 The Author(s). Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Cerebrovascular events (CVEs) are serious late adverse events among childhood cancer survivors. We estimated the incidence and risk factors of symptomatic CVEs and described the clinical characteristics among childhood cancer survivors after upper body radiotherapy. The Dutch Childhood Cancer Survivor Study LATER cohort study includes 5-year childhood cancer survivors diagnosed 50 Gy was associated with 6-fold increased risk, compared to upper body radiotherapy not involving the cranium (hazard ratio = 6.3, 95%CI: 3.3-12.1). In a subgroup with available data on lifestyle and comorbidities, hypertension (odds ratio[OR] = 6.2, 95%CI: 1.6-23.8) and obesity (BMI≥30 vs. <30 = 2.95, 95%CI: 1.1-8.0) significantly increased CVE risk. During CVE episode, 17 (16%) had a life-threatening situation, and two (2%) others died. In 28%, a second CVE developed during follow-up. At end of follow-up, 29% were deceased, and 40% of those alive were unable to carry out normal activities/active work. Childhood cancer survivors treated with higher doses of cranial radiotherapy are at highest risk for developing CVEs. CVEs occur at a young age and cause a high morbidity. Studies to investigate risk-reducing secondary preventive interventions are warranted., (© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Objective: Childhood cancer survivors (CCS) face an increased risk of early cardiovascular disease (CVD). In our nationwide CCS cohort, we assessed the prevalence and determinants of dyslipidemia, a well-established risk factor for accelerated atherosclerosis and CVD., Methods: Prevalence of dyslipidemia was cross-sectionally assessed in 2338 adult CCS and compared to adults with no cancer history (Lifelines, n = 132 226). Dyslipidemia was defined by multiple classifications as well as lipid abnormalities to investigate the impact on prevalence and determinants. Logistic regression models, adjusted for age, sex, and BMI, were used to assess the cohort effect on presence of dyslipidemia. Determinants of dyslipidemia were identified through multivariable logistic regression., Results: CCS (median age 34.7 year, median follow-up 27.1 year) had significantly increased odds of dyslipidemia compared to the reference cohort according to all classifications (NCEP-ATP-III, WHO, EGIR, CTCAEv.4.03). In survivors without lipid-lowering agents (n = 2007), lipid abnormalities were present in 20.6% (triglycerides > 1.7 mmol/L), 30.3% (HDL-c < 1.0/1.3 mmol/L (male/female)), 29.9% (total cholesterol > 5.2 mmol/L), 7.3% (LDL-c > 4.1 mmol/L), and 7.7% (apolipoprotein-B > 130 mg/dL). Compared to references without lipid-lowering agents (n = 126 631), survivors had increased odds of high triglycerides (aOR = 1.89, 95% CI = 1.68-2.13), low HDL-c (aOR = 2.73, 95% CI = 2.46-3.03), and high apolipoprotein-B (aOR = 1.84, 95% CI = 1.53-2.20). Sex, age, BMI, physical activity, abdominal/pelvic, cranial, and total body irradiation, alkylating agents, smoking, growth hormone deficiency, and diabetes mellitus were associated with (≥1 definition of) dyslipidemia in CCS., Conclusions: CCS is at increased risk of dyslipidemia, with various modifiable and non-modifiable determinants identified, underscoring the importance of survivor-specific risk assessment tools to control cardiovascular morbidity and mortality in this high-risk population., Competing Interests: Conflict of interest: None declared, (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Endocrinology.)

Purpose: Splenectomy might be a risk factor for valvular heart disease (VHD) in adult Hodgkin lymphoma survivors. As this risk is still unclear for childhood cancer survivors (CCS), the aim of this study is to evaluate the association between treatments affecting splenic function (splenectomy and radiotherapy involving the spleen) and VHD in CCS., Methods: CCS were enrolled from the DCCSS-LATER cohort, consisting of 6,165 five-year CCS diagnosed between 1963 and 2002. Symptomatic VHD, defined as symptoms combined with a diagnostic test indicating VHD, was assessed from questionnaires and validated using medical records. Differences in the cumulative incidence of VHD between CCS who received treatments affecting splenic function and CCS who did not were assessed using the Gray test. Risk factors were analyzed in a multivariable Cox proportional hazards model., Results: The study population consisted of 5,286 CCS, with a median follow-up of 22 years (5-50 years), of whom 59 (1.1%) had a splenectomy and 489 (9.2%) radiotherapy involving the spleen. VHD was present in 21 CCS (0.4%). The cumulative incidence of VHD at the age of 40 years was significantly higher in CCS who received treatments affecting splenic function (2.7%, 95% confidence interval (CI) 0.4%-4.9%) compared with CCS without (0.4%, 95% CI 0.1%-0.7%) (Gray's test, p = 0.003). Splenectomy was significantly associated with VHD in a multivariable analysis (hazard ratio 8.6, 95% CI 3.1-24.1)., Conclusions and Implications: Splenectomy was associated with VHD. Future research is needed to determine if CCS who had a splenectomy as part of cancer treatment might benefit from screening for VHD., (© 2024 The Author(s). Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Purpose: Numerous studies investigated generic psychosocial outcomes in survivors of childhood cancer (CCS). The present study aimed to describe survivor-specific psychosocial consequences in CCS, and to identify socio-demographic and medical associated factors., Methods: CCS from the Dutch Childhood Cancer Survivor Study (DCCSS)-LATER cohort (diagnosed 1963-2001) part 2 (age ≥ 18 years, diagnosed < 18 years, ≥ 5 years since diagnosis) completed the Benefit & Burden Scale (BBSC) and the Impact of Cancer-Childhood Cancer (IOC-CS). Items were scored on a 5-point Likert scale (range 1-5). We examined outcomes with descriptive statistics, and socio-demographic and medical associated factors with regression analyses, corrected for multiple testing (p < 0.004)., Results: CCS, N = 1713, age mean (M) 36 years, 49% female, ≥ 15 years since diagnosis, participated. On average, CCS reported 'somewhat' Benefit (M = 2.9), and 'not at all' to 'a little' Burden (M = 1.5) of childhood cancer. Average scores on IOC-CS' positive impact scales ranged from 2.5 (Personal Growth) to 4.1 (Socializing), and on the negative impact scales from 1.4 (Financial Problems) to 2.4 (Thinking/Memory). Apart from cognitive problems, CCS reported challenges as worries about relationship status, fertility, and how cancer had affected siblings. Female sex was associated with more Personal Growth, and more negative impact. CCS more highly educated, partnered, and employed had higher positive and lower negative impact. CCS older at diagnosis reported more positive impact. CNS tumor survivors and those who had head/cranium radiotherapy had higher negative impact. CNS tumor survivors reported less positive impact., Conclusion and Implications: The majority of CCS reported positive impact of cancer while most CCS reported little negative impact. While this may indicate resiliency in most CCS, health care providers should be aware that they can also experience survivor-specific challenges that warrant monitoring/screening, information provision and psychosocial support., (© 2023. The Author(s).)

Objective: This study examines the association between psychosocial risk and protective factors and a wide range of psychosocial outcomes including emotional, social, cognitive, and physical domains in childhood cancer survivors (CCS)., Methods: CCS from the Dutch Childhood Cancer Survivor Study (DCCSS)-LATER cohort (diagnosed 1963-2001) part 2 (age ≥ 18 years, diagnosed < 18 years, ≥ 5 years since diagnosis) completed questionnaires on psychosocial risk and protective factors (Benefit and Burden Scale, Illness Cognition Questionnaire, Rosenberg Self-Esteem Scale, and Impact of Cancer Scale), and psychosocial outcomes (Hospital Anxiety and Depression Scale, Self-Rating Scale for Post-Traumatic Stress Disorder, TNO-AZL Questionnaire for Adult Health-Related Quality of Life, and Short Form-36). Associations were assessed with regression analysis, adjusting for attained age, sex, number of health conditions, and time since diagnosis, while correcting for multiple testing (p < 0.004)., Results: A total of 1382 CCS participated, all diagnosed ≥ 15 years ago. The mean age of participating CCS was 36 years, and 51% were female. Perceived benefit and burden, acceptance, and helplessness, self-esteem and social support were associated with the psychosocial outcomes. In the models including all psychosocial factors, most associations with psychosocial outcomes were seen for self-esteem (10×), and perceived burden (9×). Self-esteem (all β ≤ 0.47) and perceived burden (all β ≤ 0.38) demonstrated strongest associations of medium/large size., Conclusions: Perceptions of childhood cancer, illness cognitions, self-esteem, and social support play a role in explaining psychosocial functioning in CCS, outweighing the influence of socio-demographic and medical variables. Addressing negative perceptions and reducing feelings of helplessness, while promoting acceptance, self-esteem, and social support, could provide intervention targets for CCS who encounter psychosocial challenges., (© 2024 The Author(s). Psycho‐Oncology published by John Wiley & Sons Ltd.)

Objective: To discover new variants associated with low ovarian reserve after gonadotoxic treatment among adult female childhood cancer survivors using a genome-wide association study approach., Design: Genome-wide association study., Setting: Not applicable., Patients: A discovery cohort of adult female childhood cancer survivors from the pan-European PanCareLIFE cohort (n = 743; median age: 25.8 years), excluding those who received bilateral ovarian irradiation, bilateral oophorectomy, central nervous system or total body irradiation, or stem cell transplantation. Replication was attempted in the US-based St. Jude Lifetime Cohort (n = 391; median age: 31.3 years)., Exposure: Female childhood cancer survivors are at risk of therapy-related gonadal impairment. Alkylating agents are well-established risk factors, and the interindividual variability in gonadotoxicity may be explained by genetic polymorphisms. Data were collected in real-life conditions, and cyclophosphamide equivalent doses were used to quantify alkylation agent exposure., Main Outcome Measure: Anti-Müllerian hormone (AMH) levels served as a proxy for ovarian function, and the findings were combined in a meta-analysis., Results: Three genome-wide significant (<5.0 × 10 -8 ) and 16 genome-wide suggestive (<5.0 × 10 -6 ) loci were associated with log-transformed AMH levels, adjusted for cyclophosphamide equivalent dose of alkylating agents, age at diagnosis, and age at study in the PanCareLIFE cohort. On the basis of the effect allele frequency (EAF) (>0.01 if not genome-wide significant), and biologic relevance, 15 single nucleotide polymorphisms were selected for replication. None of the single nucleotide polymorphisms were statistically significantly associated with AMH levels. A meta-analysis indicated that rs78861946 was associated with borderline genome-wide statistical significance (reference/effect allele: C/T; effect allele frequency: 0.04, beta (SE): -0.484 (0.091)., Conclusion: This study found no genetic variants associated with a lower ovarian reserve after gonadotoxic treatment because the findings of this genome-wide association study were not statistically significant replicated in the replication cohort. Suggestive evidence for the potential importance of 1 variant is briefly discussed, but the lack of statistical significance calls for larger cohort sizes. Because the population of childhood cancer survivors is increasing, large-scale and systematic research is needed to identify genetic variants that could aid predictive risk models of gonadotoxicity as well as fertility preservation options for childhood cancer survivors., Competing Interests: Declaration of Interests M.E.M.v.d.P. reports funding from European Union’s Seventh Framework Programme for research (technological development, and demonstration funding), Dutch Cancer Society (grant no. VU 2006-3622), Princess Máxima Center Foundation, and Stichting Kinderoncologisch Centrum Rotterdam (sKOCR), DCOG-LATER VEVO study was funded by the Dutch Cancer Society (grant no. VU 2006-3622) and by the Children Cancer-Free Foundation (Project no. 20) and the St Jude Lifetime Cohort study by NCI U01 CA195547. L.B. has nothing to disclose. Y.Y. reports funding from National Cancer Institute (NCI) U01CA195547 (MPI: Hudson/Ness), St. Jude Lifetime Cohort Study (SJLIFE), NCI P30CA021765 (PI: Roberts) Cancer Center Support Grant (CCSG), and American Lebanese Syrian Associated Charities for the submitted work; funding from NCI U24CA055727 (PI: Armstrong) Childhood Cancer Survivor Study (CCSS), National Institutes of Health (NIH) R03DE029238 (PI: Li/Sun) Innovative Statistical Analysis for Genome-Wide Data with General Interval Censored Outcomes of Oral Health in Childhood Cancer Survivors, NCI R01CA216354 (MPI: Yasui/Zhang) Late Effects Prediction Using Clinical Phenotypes and Whole Genome Sequencing, St Jude Lifetime Cohort study by NCI U01 CA195547, NCI R01CA270157 (MPI: Bhakta/Yasui) Measuring Lifelong Multimorbidity with Patient Perspectives: Implementing and Visualizing the Cumulative Burden Methodology Across Cohorts, NCI R01CA258193 (MPI: Huang/Yasui) Patient-Generated Health Data to Predict Childhood Cancer Survivorship Outcomes (HEALTHSHARE), NIH &MD Anderson Cancer Center R01CA261750-01A1 (MPI: Howell/Mulrooney/Yasui) Personalized Risk Prediction to Reduce Cardiovascular Disease in Childhood Cancer Survivors, NCI &Northwestern University R01CA261898 (MPI: Burridge/Sapkota) Predicting and Preventing Chemotherapy-Induced Cardiotoxicity in African American Children, NC. J.S.E.L. has nothing to disclose. L.L.R. has nothing to disclose. W.J.E.T. has nothing to disclose. B.V. has nothing to disclose. B.V. has nothing to disclose. D.B. has nothing to disclose. G.J.L.K. has nothing to disclose. C.B.L. has nothing to disclose. A.O. has nothing to disclose. J.J.L. has nothing to disclose. C.C.M.B. has nothing to disclose. J.B. has nothing to disclose. C.B. has nothing to disclose. E.C. has nothing to disclose. E.v.D.-d.B. has nothing to disclose. U.D. has nothing to disclose. H.J.v.d.P. has nothing to disclose. A.C.H.d.V. has nothing to disclose. J.F.W. has nothing to disclose. A.R. has nothing to disclose. S.D.F. has nothing to disclose. D.G. has nothing to disclose. M.M. has nothing to disclose. M.K. has nothing to disclose. T.K. has nothing to disclose. J.K. has nothing to disclose. D.M.-M. has nothing to disclose. C.S. has nothing to disclose. O.Z. has nothing to disclose. P.K. has nothing to disclose. L.C.M.K. has nothing to disclose. R.J.B. has nothing to disclose. F.W. has nothing to disclose. J.L.B. has nothing to disclose. A.G.U. has nothing to disclose. A.M.E.B. has nothing to disclose. F.E.v.L. has nothing to disclose. K.K.N. has nothing to disclose. M.M.H. has nothing to disclose. A.-L.L.F.v.d.K. has nothing to disclose. M.M.v.d.H.E. has nothing to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Acute lymphoblastic leukemia (ALL) survivors are at risk for developing subsequent neoplasms, but there is limited information on long-term risks and risk factors for both subsequent malignant neoplasms (SMNs) and subsequent non-malignant neoplasms (SNMNs). We analyzed long-term risk and risk factors for SMNs and SNMNs among 3291 5-year ALL survivors from the Dutch Childhood Cancer Survivor Study-LATER cohort (1963-2014). We calculated standardized incidence ratios (SIRs) and cumulative incidences and used multivariable Cox proportional hazard regression analyses for analyzing risk factors. A total of 97 survivors developed SMNs and 266 SNMNs. The 30-year cumulative incidence was 4.1% (95%CI: 3.5-5.3) for SMNs and 10.4%(95%CI: 8.9-12.1) for SNMNs. Risk of SMNs was elevated compared to the general population (SIR: 2.6, 95%CI: 2.1-3.1). Survivors treated with hematopoietic stem cell transplantation (HSCT) with total body irradiation (TBI) (HR:4.2, 95%CI: 2.3-7.9), and without TBI (HR:4.0,95%CI: 1.2-13.7) showed increased SMN risk versus non-transplanted survivors. Cranial radiotherapy (CRT) was also a risk factor for SMNs (HR:2.1, 95%CI: 1.4-4.0). In conclusion, childhood ALL survivors have an increased SMN risk, especially after HSCT and CRT. A key finding is that even HSCT-treated survivors without TBI treatment showed an increased SMN risk, possibly due to accompanied chemotherapy treatment. This emphasizes the need for careful follow-up of HSCT and/or CRT-treated survivors., (© 2024. The Author(s).)

Background: The objective of this study was to examine the prevalence of unhealthy lifestyle behaviors, overweight, and obesity in Dutch childhood cancer survivors (CCSs) compared with sibling controls and the Dutch general population. Other aims were to assess associated factors of unhealthy lifestyle behaviors, overweight, and obesity and to identify subgroups of CCSs at risk for these unhealthy statuses., Methods: The authors included 2253 CCSs and 906 siblings from the Dutch Childhood Cancer Survivor Study-Late Effects After Childhood Cancer cohort, part 1, and added data from the Dutch general population. Questionnaire data were collected on overweight and obesity (body mass index >25.0 kg/m 2 ), meeting physical activity guidelines (>150 minutes per week of moderate or vigorous exercises), excessive alcohol consumption (>14 and >21 alcoholic consumptions per week for women and men, respectively), daily smoking, and monthly drug use. Multivariable logistic regression analyses and two-step cluster analyses were performed to examine sociodemographic-related, health-related, cancer-related, and treatment-related associated factors of unhealthy lifestyle behaviors and to identify subgroups of CCSs at risk for multiple unhealthy behaviors., Results: CCSs more often did not meet physical activity guidelines than their siblings (30.0% vs. 19.3%; p < .001). Married as marital status, lower education level, nonstudent status, and comorbidities were common associated factors for a body mass index ≥25.0 kg/m 2 and insufficient physical activity, whereas male sex and lower education were shared associated factors for excessive alcohol consumption, daily smoking, and monthly drug use. A subgroup of CCSs was identified as excessive alcohol consumers, daily smokers, and monthly drug users., Conclusions: The current results emphasize the factors associated with unhealthy behaviors and the potential identification of CCSs who exhibit multiple unhealthy lifestyle behaviors., (© 2024 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Purpose: Investigate the association between presence, number and type of clinically relevant health conditions and a range of psychosocial outcomes (emotional, social, cognitive, physical) in survivors of childhood cancer (CCS)., Methods: CCS from the Dutch Childhood Cancer Survivor Study (DCCSS)-LATER cohort (diagnosed between 1963-2001, attained age ≥ 18, diagnosed < 18, ≥ 5 years since diagnosis) completed a questionnaire on health conditions (2013-2014), and questionnaires on psychosocial outcomes (2017-2020): Hospital Anxiety and Depression Scale, Short form 36, TNO-AZL Questionnaire for Adult Health-Related Quality of Life, and the Self-Rating Scale for Post-Traumatic Stress Disorder. Associations among health conditions and psychosocial outcomes were assessed with regression analysis, adjusting for attained age, sex, and time since diagnosis, and adjusting for multiple testing (p < 0.004)., Results: A total of 1437 CCS, mean age 36.3 years, 51.1% female, ≥ 15 years since diagnosis, completed questionnaires on health and psychosocial outcomes. CCS with a clinically relevant health condition, and those with more conditions had worse emotional, social, and physical outcomes; regression coefficients were small to moderate. CCS with gastro-intestinal conditions, endocrine, nervous systems, eye, or ear conditions, and especially those with secondary malignant neoplasms, reported worse psychosocial functioning; regression coefficients were small/moderate to large., Conclusion and Implications: Health care professionals should be aware of the increased risk for psychosocial problems among CCS with health conditions, especially for survivors with secondary malignant neoplasms, gastro-intestinal, endocrine, nervous system, eye, and ear conditions. CCS may benefit from psychological interventions to develop coping strategies to manage health conditions and psychosocial consequences of the cancer trajectory., (© 2024. The Author(s).)

Introduction: The aim of the current study was to investigate whether subtypes of chronic fatigue (CF) can be identified in childhood cancer survivors (CCS), and if so, to determine the characteristics of participants with a specific subtype., Methods: Participants were included from the nationwide DCCSS LATER cohort. The Checklist Individual Strength (CIS) was completed to assess fatigue. Participants with CF (scored ≥35 on the fatigue severity subscale and indicated to suffer from fatigue for ≥6 months) were divided into subgroups using two-step cluster analysis based on the CIS concentration, motivation, and physical activity subscales. Differences between groups on demographics, psychosocial, lifestyle, and treatment-related variables were determined using ANOVA and chi-square analyses (univariable) and multinomial regression analysis (multivariable)., Results: A total of 1910 participants participated in the current study (n = 450 with CF; n = 1460 without CF). Three CF subgroups were identified: Subgroup 1 (n = 133, 29% of participants) had CF with problems in physical activity; Subgroup 2 (n = 111, 25% of participants) had CF with difficulty concentrating; and Subgroup 3 (n = 206, 46% of participants) had multi-dimensional CF. Compared to Subgroup 1, Subgroup 2 more often reported sleep problems, limitations in social functioning, and less often have more than two comorbidities. Subgroup 3 more often reported depression, sleep problems, a lower self-esteem, and limitations in social functioning and a lower educational level compared to Subgroup 1., Conclusion: Different subgroups of CCS with CF can be identified based on fatigue dimensions physical activity, motivation and concentration. Results suggest that different intervention strategies, tailored for each subgroup, might be beneficial., (© 2024 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Background: We assessed the prevalence and diagnostic value of ECG abnormalities for cardiomyopathy surveillance in childhood cancer survivors., Methods: In this cross-sectional study, 1381 survivors (≥5 years) from the Dutch Childhood Cancer Survivor Study part 2 and 272 siblings underwent a long-term follow-up ECG and echocardiography. We compared ECG abnormality prevalences using the Minnesota Code between survivors and siblings, and within biplane left ventricular ejection fraction (LVEF) categories. Among 880 survivors who received anthracycline, mitoxantrone or heart radiotherapy, logistic regression models using least absolute shrinkage and selection operator identified ECG abnormalities associated with three abnormal LVEF categories (<52% in male/<54% in female, <50% and <45%). We assessed the overall contribution of these ECG abnormalities to clinical regression models predicting abnormal LVEF, assuming an absence of systolic dysfunction with a <1% threshold probability., Results: 16% of survivors (52% female, mean age 34.7 years) and 14% of siblings had major ECG abnormalities. ECG abnormalities increased with decreasing LVEF. Integrating selected ECG data into the baseline model significantly improved prediction of sex-specific abnormal LVEF (c-statistic 0.66 vs 0.71), LVEF <50% (0.66 vs 0.76) and LVEF <45% (0.80 vs 0.86). While no survivor met the preset probability threshold in the first two models, the third model used five ECG variables to predict LVEF <45% and was applicable for ruling out (sensitivity 93%, specificity 56%, negative predictive value 99.6%). Calibration and internal validation tests performed well., Conclusion: A clinical prediction model with ECG data (left bundle branch block, left atrial enlargement, left heart axis, Cornell's criteria for left ventricular hypertrophy and heart rate) may aid in ruling out LVEF <45%., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Childhood cancer survivors at risk for heart failure undergo lifelong echocardiographic surveillance. Previous studies reported the limited diagnostic accuracy of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) in detecting left ventricular (LV) dysfunction. However, potential enhanced diagnostic accuracy through the combination of biomarkers and clinical characteristics has been suggested., Objectives: The aim of this study was to develop and internally validate a diagnostic model that combines cardiac biomarkers with clinical characteristics for effectively ruling in or ruling out LV dysfunction in childhood cancer survivors., Methods: A multicenter cross-sectional study included 1,334 survivors (median age 34.2 years) and 278 siblings (median age 36.8 years). Logistic regression models were developed and validated through bootstrapping, combining biomarkers with clinical characteristics., Results: Abnormal NT-proBNP levels were observed in 22.1% of survivors compared with 5.4% of siblings, whereas hs-cTnT levels exceeding 10 ng/L were uncommon in both survivors (5.9%) and siblings (5.0%). The diagnostic models demonstrated improvement upon the addition of NT-proBNP and hs-cTnT to clinical characteristics, resulting in an increased C statistic from 0.69 to 0.73 for LV ejection fraction (LVEF) <50% and a more accurate prediction of more severe LV dysfunction, with the C statistic increasing from 0.80 to 0.86 for LVEF <45%. For LVEF <50% (prevalence 10.9%), 16.9% of survivors could be effectively ruled out with high sensitivity (95.4%; 95% CI: 90.4%-99.3%) and negative predictive value (97.5%; 95% CI: 94.6%-99.7%). Similarly, for LVEF <45% (prevalence 3.4%), 53.0% of survivors could be ruled out with moderate to high sensitivity (91.1%; 95% CI: 79.2%-100%) and high negative predictive value (99.4%; 95% CI: 98.7%-100%)., Conclusions: The biomarker-based diagnostic model proves effective in ruling out LV dysfunction, offering the potential to minimize unnecessary surveillance echocardiography in childhood cancer survivors. External validation is essential to confirm these findings. (Early Detection of Cardiac Dysfunction in Childhood Cancer Survivors; A DCOG LATER Study; https://onderzoekmetmensen.nl/nl/trial/23641)., Competing Interests: This research was supported by the Dutch Heart Foundation (CVON2015-21) and Stichting Kinderen Kankervrij/ODAS Stichting. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Background: The aim of this study is to evaluate how cumulative burden of clinically relevant, self-reported outcomes in childhood cancer survivors (CCSs) compares to a sibling control group and to explore how the burden corresponds to levels of care proposed by existing risk stratifications., Methods: The authors invited 5925 5-year survivors from the Dutch Childhood Cancer Survivor Study (DCCSS LATER) cohort and their 1066 siblings to complete a questionnaire on health outcomes. Health outcomes were validated by self-reported medication use or medical record review. Missing data on clinically relevant outcomes in CCSs for whom no questionnaire data were available were imputed with predictive mean matching. We calculated the mean cumulative count (MCC) for clinically relevant outcomes. Furthermore, we calculated 30-year MCC for groups of CCSs based on primary cancer diagnosis and treatment, ranked 30-year MCC, and compared the ranking to levels of care according to existing risk stratifications., Results: At median 18.5 years after 5-year survival, 46% of CCSs had at least one clinically relevant outcome. CCSs experienced 2.8 times more health conditions than siblings (30-year MCC = 0.79; 95% confidence interval [CI], 0.74-0.85 vs. 30-year MCC = 0.29; 95% CI, 0.25-0.34). CCSs' burden of clinically relevant outcomes consisted mainly of endocrine and vascular conditions and varied by primary cancer type. The ranking of the 30-year MCC often did not correspond with levels of care in existing risk stratifications., Conclusions: CCSs experience a high cumulative burden of clinically relevant outcomes that was not completely reflected by current risk stratifications. Choices for survivorship care should extend beyond primary tumor and treatment parameters, and should consider also including CCSs' current morbidity., (© 2023 American Cancer Society.)

In recent years, the five-year survival rate for childhood cancer has increased to about 80%. However, childhood cancer therapy can have serious long-term adverse effects on general health later in life. Of survivors, 75% experience 1 or more late effects. This PhD research aimed to gain more insight into the long-term effects on oral health of childhood cancer therapy, 15 years or more after diagnosis. This study, which is part of the Dutch Childhood Cancer Survivor Study Late Effects 2 (DCCSS LATER 2 Study), showed that oral complications such as dental developmental disorders and hyposalivation occur frequently. Most important risk factors were head and neck radiotherapy of the salivary glands, (alkylating) cytostatic agents, and age at the time of the cancer diagnosis. Dentists should be aware of childhood cancer in the medical history of their patient and of the type of therapy received. Regular dental visits are an essential part of long-term follow-up care of childhood cancer survivors.

Background: Treatment-related gonadal dysfunction leading to fertility problems is a frequently encountered late effect in childhood cancer survivors (CCSs). This study evaluated reproductive outcomes and reproductive health care utilization among male CCSs compared with male siblings., Methods: A nationwide cohort study was conducted as part of the Dutch Childhood Cancer Survivor LATER study part 1, a questionnaire and linkage study. A questionnaire addressing reproductive outcomes and reproductive health care was completed by 1317 male CCSs and 407 male siblings. A total of 491 CCSs and 185 siblings had a previous or current desire for children and were included in this study., Results: Fewer CCSs had biological children compared with siblings (65% vs. 88%; p < .001). The type of conception by men who fathered a child was comparable between CCSs and siblings (spontaneous conception of 90% of both groups; p = .86). The percentage of men who had consulted a reproductive specialist because of not siring a pregnancy was higher in CCSs compared with siblings (34% vs. 12%; p < .001). Following consultation, fewer CCSs underwent assisted reproductive techniques (ART) compared with siblings (41% vs. 77%; p = .001). After ART, fewer CCSs fathered a child compared with siblings (49% vs. 94%; p = .001)., Conclusions: More male survivors consult a reproductive specialist, but fewer survivors undergo ART and father a child after ART compared with siblings. This insight is important for understanding potential problems faced by survivors regarding family planning and emphasizes the importance of collaboration between oncologists and reproductive specialists., (© 2023 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Juvenile myelomonocytic leukaemia (JMML) is characterized by gene variants that deregulate the RAS signalling pathway. Children with neurofibromatosis type 1 (NF-1) carry a defective NF1 allele in the germline and are predisposed to JMML, which presumably requires somatic inactivation of the NF1 wild-type allele. Here we examined the two-hit concept in leukaemic cells of 25 patients with JMML and NF-1. Ten patients with JMML/NF-1 exhibited a NF1 loss-of-function variant in combination with uniparental disomy of the 17q arm. Five had NF1 microdeletions combined with a pathogenic NF1 variant and nine carried two compound-heterozygous NF1 variants. We also examined 16 patients without clinical signs of NF-1 and no variation in the JMML-associated driver genes PTPN11, KRAS, NRAS or CBL (JMML-5neg) and identified eight patients with NF1 variants. Three patients had microdeletions combined with hemizygous NF1 variants, three had compound-heterozygous NF1 variants and two had heterozygous NF1 variants. In addition, we found a high incidence of secondary ASXL1 and/or SETBP1 variants in both groups. We conclude that the clinical diagnosis of JMML/NF-1 reliably indicates a NF1-driven JMML subtype, and that careful NF1 analysis should be included in the genetic workup of JMML even in the absence of clinical evidence of NF-1., (© 2023 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

With diagnostic and therapeutic advances, over 80% of children diagnosed with cancer become long-term survivors. As the number of childhood cancer survivors (CCS) continues to increase, dental practitioners become more likely to have CCS among their patients. CCS may develop late complications from damage caused by their cancer treatment to endocrine, cardiovascular, musculoskeletal, and other organ systems. These complications may surface decades after the completion of treatment. Adverse outcomes of childhood cancer treatment frequently involve oral and craniofacial structures including the dentition. Tooth development, salivary gland function, craniofacial growth, and temporomandibular joint function may be disturbed, increasing oral health risks in these individuals. Moreover, CCS are at risk of developing subsequent malignancies, which may manifest in or near the oral cavity. It is important that dental practitioners are aware of the childhood cancer history of their patients and have knowledge of potential late complications. Therefore, this narrative review aims to inform dental practitioners of late oral complications of cancer treatment modalities commonly used in pediatric oncology. Furthermore, selected common non-oral late sequelae of cancer therapy that could have an impact on oral health and on delivering dental care will be discussed.

Allogeneic hematopoietic cell transplantation (HCT) remains the only cure for the hematologic manifestations of Fanconi anemia (FA). We performed retrospective predictor analyses for HCT outcomes in FA for pediatric and young adult patients transplanted between 2007 and 2020 across three large referral institutions. Eighty-nine patients, 70 with bone marrow failure +/- cytogenetic abnormalities, 19 with MDS/AML, were included. Five-year overall survival (OS) was 83.2% and event-free survival (EFS) was 74%. Age ≥19, HLA mismatch and year of HCT were multivariable predictors (MVPs) for OS, EFS and treatment-related mortality (TRM). In the pediatric group, TCD was a borderline MVP (P = 0.059) with 5-year OS of 73.0% in TCD vs. 100% for T-replete HCT. The cumulative incidence of day 100 grade II-IV aGvHD and 5-year cGvHD were 5.6% and 4.6%, respectively. Relapse in the MDS/AML subgroup occurred in 4 patients (16%). Graft failure was seen in 9 patients (TCD 6/37 [16%]; T-replete 3/52 [5.7%]). Six patients developed malignancy after HCT. Survival chances after HCT for FA are excellent and associated with high engrafted survival and low toxicity. Age ≥19, HLA mismatch, year of transplant and 'TCD in the <19 years group' (although borderline) were found to be negative predictors for survival., (© 2023. The Author(s).)

Background: The purpose of this study was to determine factors associated with chronic fatigue (CF) in childhood cancer survivors (CCS)., Patients and Methods: Participants were included from the Dutch Childhood Cancer Survivor Study (DCCSS) LATER cohort, a nationwide cohort of CCS (≥5 years after diagnosis) and siblings as controls. Fatigue severity was assessed with the 'fatigue severity subscale' of the Checklist Individual Strength ('CIS-fatigue'). CF was defined as scoring ≥35 on the 'CIS-fatigue' and having fatigue symptoms for ≥6 months. Twenty-four parameters were assessed, categorized into assumed fatigue triggering, maintaining and moderating factors. Multivariable logistic regression analyses were carried out to investigate the association of these factors with CF., Results: A total of 1927 CCS participated in the study (40.7% of invited cohort), of whom 23.6% reported CF (compared with 15.6% in sibling controls, P < 0.001). The following factors were associated with CF: obesity [versus healthy weight, odds ratio (OR) 1.93; 95% confidence interval (CI) 1.30-2.87], moderate physical inactivity (versus physical active, OR 2.36; 95% CI 1.67-3.34), poor sleep (yes versus no, OR 2.03; 95% CI 1.54-2.68), (sub)clinical anxiety (yes versus no, OR 1.55; 95% CI 1.10-2.19), (sub)clinical depression (yes versus no, OR 2.07; 95% CI 1.20-3.59), pain (continuous, OR 1.49; 95% CI 1.33-1.66), self-esteem (continuous, OR 0.95; 95% CI 0.92-0.98), helplessness (continuous, OR 1.13; 95% CI 1.08-1.19), social functioning (continuous, OR 0.98; 95% CI 0.97-0.99) and female sex (versus male sex, OR 1.79; 95% CI 1.36-2.37)., Conclusion: CF is a prevalent symptom in CCS that is associated with several assumed maintaining factors, with lifestyle and psychosocial factors being the most prominent. These are modifiable factors and may therefore be beneficial to prevent or reduce CF in CCS., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)