Radiological follow-up of osteonecrosis lesions in children and adolescents with Hodgkin lymphoma.

Osteonecrosis (ON) is a common complication of glucocorticoid-based Hodgkin lymphoma (HL) treatment, but the natural evolution and prognosis of ON lesions remain poorly understood. We describe the radiological evolution of ON lesions identified in a Nordic population-based cohort of paediatric HL patients. Magnetic resonance images of suspected ON lesions were centrally reviewed to confirm ON diagnosis and grade the ON lesions according to the Niinimäki classification. The study included 202 ON lesions in 46 patients, of which 77 were joint lesions. Follow-up images were available for 146/202 lesions, with a mean follow-up time of 28 months. During follow-up, 71% of the lesions remained stable, 26% improved or resolved, and 3% progressed. A higher ON grade at diagnosis was associated with a lower likelihood of spontaneous resolution. The likelihood for resolution of ON decreased by 50% for each year of added patient age, when adjusted for sex, ON location, and symptoms. Hip ON showed less spontaneous improvement compared with other joints, and the risk for surgery was 13-fold in hip ON. Grades 3-4 joint ON has the potential to either progress or resolve, warranting follow-up in patients with severe symptoms. Research on secondary prevention should be directed at grade 3-4 joint ON.

Symptomatic osteonecrosis in children treated for Hodgkin lymphoma: A population-based study in Sweden, Finland, and Denmark.

BACKGROUND: Osteonecrosis (ON) is a potentially disabling skeletal complication of cancer treatment. Although symptomatic osteonecrosis (sON) is well-known in acute lymphoblastic leukemia (ALL), with an incidence around 6%, studies on sON in pediatric Hodgkin lymphoma (HL) are scarce. The aim of this study was to examine the incidence, risk factors, and outcome of sON in children treated for HL. PROCEDURE: A total of 490 children under 18, diagnosed with HL between 2005 and 2019 in Sweden, Finland, and Denmark were eligible for the study. Data on patient characteristics, HL treatment, and development of sON were collected from patients' medical records. Magnetic resonance imaging scans were used to establish ON diagnosis and grade ON according to the Niinimäki grading system. RESULTS: Cumulative 2-year incidence of sON among the 489 included patients was 5.5% (n = 30). The risk for developing sON was higher for those with older age (odds ratio [OR] 1.25, 95% confidence interval [CI]: 1.05-1.49, p < .010), female sex (OR 4.45, CI 1.87-10.58, p < .001), high total cumulative glucocorticoid (GC) doses (OR 1.76, 95% CI: 1.21-2.56, p = 0.003), and advanced HL (OR 2.19, 95% CI: 1.03-4.65, p = .042). Four (13.3%) patients underwent major surgical procedures and 13 (43.3%) had persistent symptoms due to ON at follow-up. CONCLUSIONS: This study shows that sON is as common in pediatric HL as in pediatric ALL, with risk factors such as older age, female sex, high cumulative GC doses, and advanced HL. Future HL protocol development should aim to reduce the burden of ON by modifying GC treatment.

Hodgkin lymphoma in children, adolescents and young adults - a comparative study of clinical presentation and treatment outcome.

BACKGROUND: Hodgkin lymphoma (HL) treatment protocols for children, adolescents and young adults traditionally differ, but the biological and clinical justification for this remains uncertain. MATERIAL AND METHODS: We compared age-dependent clinical presentation and treatment and outcome for 1072 classical HL patients 0-24 years diagnosed in Denmark (1990-2010) and Sweden (1992-2009) in pediatric (n = 315, Denmark <15 years, Sweden <18 years) or adult departments (n = 757). Distribution of clinical characteristics was assessed with Pearson's chi2-test and Mantel-Haenszel trend test. The Kaplan-Meier method was used for survival analyses. Hazard ratios (HR) were used to compare the different treatment groups and calculated using Cox regression. RESULTS: Children (0-9 years) less often presented with advanced disease than adolescents (10-17 years) and young adults (18-24 years) (stage IIB-IV: children 32% vs. adolescents 50%, and adults 55%; p < .005). No variation in overall survival (OS) was seen between pediatric and adult departments or by country. Danish pediatric patients received radiotherapy (36%) less frequently than Swedish pediatric patients (71%) (p < .0001). Ten-year event-free survival (EFS) was lower among Danish pediatric patients (0-14 years) (0.79; 95% confidence interval (CI) 0.70-0.86) than among Swedish pediatric patients (0-17 years) (0.88; 95% CI 0.83-0.92), HR (1.93; 95% CI 1.08-3.46). A similar pattern was seen between adult patients in the two countries: Denmark 10-year EFS 0.85 (95% CI 0.81-0.88), Sweden 0.88 (95% CI 0.84-0.91), adjusted HR 1.51 (95% CI 1.03-2.22). CONCLUSION: Adolescents and young adults shared similar clinical presentation suggesting a rationale of harmonized treatment for these groups. Both adult and pediatric protocols provided high OS with no significant difference between the departments. The less frequent use of radiotherapy in Danish pediatric patients corresponded to a lower EFS, but comparable OS in all groups confirmed effective rescue strategies for the relapsing patients.

The role of tumour-infiltrating eosinophils, mast cells and macrophages in Classical and Nodular Lymphocyte Predominant Hodgkin Lymphoma in children.

OBJECTIVES: To study Hodgkin lymphoma (HL) microenvironment in a Swedish paediatric population and its relation to clinical parameters. METHODS: Tumour tissue from classical HL (cHL) (n = 87) and nodular lymphocyte predominant HL (NLPHL) (n = 11) was investigated for Epstein-Barr Virus (EBV) and analysed for eosinophils, mast cells and macrophages. RESULTS: In cHL, EBV positivity was more common in low age (P < 0.001) and in mixed cellularity (MC) (P < 0.001). Higher mast cell infiltration was seen in stage III-IV (P < 0.001), and with presence of B-symptoms (P = 0.01). Cases with high mast cell counts displayed higher erythrocyte sedimentation rate (ESR), lower haemoglobin and albumin levels. Higher macrophage infiltration was seen in stage III-IV (P = 0.02) and there was elevated ESR and neutrophil count. All NLPHL cases were EBV negative, had lower rates of inflammatory cells and lower degree of inflammatory reaction in laboratory parameters. There was no difference in survival estimates with regard to infiltration of inflammatory cells. CONCLUSIONS: Higher levels of mast cells and macrophages in cHL tumours reflected the clinical presentation in laboratory parameters, B-symptoms and more advanced stages. NLPHL differs from cHL in numbers of inflammatory cells in the tumour, and in laboratory parameters.

Hodgkin lymphoma--a survey of children and adolescents treated in Sweden 1985-2009.

BACKGROUND: Hodgkin lymphoma (HL) in children constitutes approximately 30% of all pediatric lymphomas in Sweden. The chance of cure is high, but the frequency of late effects has been considerable. Over recent years, efforts have been made to reduce treatment with maintained survival. MATERIAL AND METHODS: All patients 0-17 years, identified in the Swedish Childhood Cancer Register as diagnosed between 1985 and 2009, were included. The material was analyzed using descriptive statistics and for survival estimates the Kaplan-Meier method was used. RESULTS: Three hundred and thirty-four patients were identified during this time period. The median age was 14 years. Male sex was over-represented, especially in lower age groups and in nodular lymphocyte predominant Hodgkin lymphoma (NLPHL). In nodular sclerosis and in age group 15-17 years, female sex dominated. Most of the cases presented in stages I or II. B-symptoms were present in 38% of cHL, but only in 7% of NLPHL. The number of patients receiving radiotherapy has been significantly reduced during the period studied. The relapse rate in cHL was 10 ± 2% and in NLPHL 16 ± 7%. The relapse rate was significantly higher in cHL stage IIB compared to other stages in the same therapy group. In cHL 6% died, and in NLPHL 0%. The 5-, 10- and 20-year overall survival estimates in cHL were 96 ± 1%, 95 ± 1% and 90 ± 3%, respectively, with no significant difference when comparing different treatment regimens and time periods. The 5- and 10-year overall survival after relapse in cHL was 81 ± 8% and 75 ± 10%, respectively. CONCLUSION: During the period studied there is no indication of a decline in survival despite changes in treatment. Survival rates in Sweden are high, and even after relapse chances of cure are high. We were not able to identify any characteristics specific for the group of patients that did not survive.

Changes in mortality and causes of death in the Swedish Down syndrome population.

During the past few decades age at death for individuals with Down syndrome (DS) has increased dramatically. The birth frequency of infants with DS has long been constant in Sweden. Thus, the prevalence of DS in the population is increasing. The aim of the present study was to analyze mortality and causes of death in individuals with DS during the period 1969-2003. All individuals with DS that died between 1969 and 2003 in Sweden, and all individuals born with DS in Sweden between 1974 and 2003 were included. Data were obtained from the Swedish Medical Birth Register, the Swedish Birth Defects Register, and the National Cause of Death Register. Median age at death has increased by 1.8 years per year. The main cause of death was pneumonia. Death from congenital heart defects decreased. Death from atherosclerosis was rare but more frequent than reported previously. Dementia was not reported in any subjects with DS before 40 years of age, but was a main or contributing cause of death in 30% of the older subjects. Except for childhood leukemia, cancer as a cause of death was rare in all age groups. Mortality in DS, particularly infant mortality, has decreased markedly during the past decades. Median age at death is increasing and is now almost 60 years. Death from cancer is rare in DS, but death from dementia is common.

Distribution of hospital care among pediatric and young adult Hodgkin lymphoma survivors-A population-based cohort study from Sweden and Denmark.

The burden of late effects among Hodgkin lymphoma (HL) survivors treated according to contemporary protocols remains poorly characterized. We used nation-wide registers to assess number of inpatient bed-days and specialist outpatient visits among 1048 HL-patients (<25 years, diagnosed 1990-2010) and 5175 country-, sex-, and age-matched comparators. We followed them for up to 24 years, with time-dependent assessment of relapse status. International Classification of Diseases (ICD-10) chapter-specific hazard ratios (HRs) were assessed in Cox regression analyses, and nonparametric statistics described patterns of health-care-use. Relative to comparators, relapse-free survivors were at increased risk of infections, diseases of the blood, endocrine, circulatory and respiratory systems, and unspecific symptoms, HRs ranging from 1.86 to 3.05. Relative to comparators, relapsed survivors had at statistically significantly increased risk of diseases reflecting practically all investigated disease-chapters, HRs ranging from 1.60 to 18.7. Among relapse-free survivors, 10% of the patients accounted for 80% of all hospital bed days, and 55% were never hospitalized during follow-up. Among relapsed-survivors, 10% of the patients accounted for 50% of the bed days, and only 24% were never hospitalized during follow-up. In contrast, 10% of the comparators accounted for 90% of hospital bed days and 75% were never hospitalized. These findings challenge the impression of a uniformly distributed long-term morbidity among all HL survivors and emphasize the need for early identification and attention to patients particularly susceptible to late effects, such as relapsed survivors.