Adult Hodgkin lymphoma incidence trends in the United States from 2000 to 2020.

Hodgkin lymphoma (HL) is a rare malignancy affecting the lymphatic system. Our study examined the incidence rates of adult HL based on sex, race/ethnicity, age, and histological subgroups in the United States (US) from 2000 to 2020. Data for this study were extracted from the Surveillance, Epidemiology, and End Results 22 database. HL patients were identified utilizing the International Classification of Diseases for Oncology version 3 and categorized as classical HL, lymphocyte-rich/mixed cell/lymphocyte depleted, nodular sclerosis, classical HL, not otherwise specified, and nodular lymphocyte-predominant HL. The study reported average annual percent change (AAPC). All estimates were presented as counts and age-standardized incidence rates (ASIRs) per 100,000 individuals. Between 2000 and 2019, a total of 70,924 cases of HL were reported in the US. Classical HL was the predominant subtype (94.27%), and most incident cases were among non-Hispanic Whites (66.92%) and those aged 20-29 years (24.86%). The ASIR per 100,000 population was 3.83 for men and 2.92 for women. Both sexes showed declines in the AAPCs between 2000 and 2019 (- 0.64% [- 0.99, - 0.28] and - 0.40% [- 0.77, - 0.03] for men and women, respectively). There was a significant decrease in ASIRs after COVID-19 among both sexes (percent change: - 7.49% [- 11.58, - 3.40]). Throughout all age groups, men had a higher incidence rate compared to women, except for those aged 20-29 years. Although the overall HL incidence rate was lowered in the study period from 2000 to 2019, a dramatic decrease in ASIRs of HL patients following COVID-19 pandemic was observed.

The causal effect of telomere length on the risk of malignant lymphoma: A Mendelian randomization study.

Telomere length (TL) has been implicated in the risk assessment of numerous cancers in observational studies. Nevertheless, the relationship between TL and malignant lymphoma remains unclear, displaying inconsistent patterns across different studies. A summary dataset for genome-wide association study of TL and malignant lymphoma was acquired from the OpenGWAS website. An extensive 2-sample Mendelian randomization (MR) analysis was performed, encompassing various methodologies such as MR-Egger, weighted median, weighted mode, simple mode, and the primary method of inverse-variance weighting (IVW). Sensitivity evaluations were performed using the Cochran Q test, MR-Egger regression, and leave-one-out analysis. The main method IVW revealed that TL substantially increased the risk of Hodgkin lymphoma (HL; odds ratio [OR] = 2.135; 95% confidence interval [CI] = 1.181-3.859; P = .012). Both the IVW and weighted median methods indicated statistical associations between genetically predicted TL and other types of non-HL (OR = 1.671, 95% CI = 1.009-2.768, P = .045; OR = 2.310, 95% CI = 1.033-5.169, P = .042). However, there was no association between TL and diffuse large B-cell lymphoma, follicular lymphoma, or mature T/natural Killer-cell lymphoma, and sensitivity analysis revealed no heterogeneity or horizontal pleiotropy, indicating that the causal effect was robust. Our study shows that TL plays different roles in different types of lymphomas. A longer TL significantly increases the risk of HL and other types of non-HL.

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.

Sociodemographic and Socioeconomic Factors Correlate with Late-Stage Pediatric Hodgkin Lymphoma and Rhabdomyosarcoma: A Report from the Children's Oncology Group Registries.

BACKGROUND: We examined the association between late-stage diagnosis and individual- and community-level sociodemographic and socioeconomic characteristics among patients with pediatric Hodgkin lymphoma and rhabdomyosarcoma (RMS). METHODS: We obtained Children's Oncology Group data from 1999 to 2021 including summary stage [local (L), regional (R), and distant (D)], tumor subtype, demographics, and ZIP Code at diagnosis. We linked ZIP Codes to county-level redlining scores (C, D = greatest redlining), the Child Opportunity Index, and measures of segregation (racial dissimilarity indices). Logistic regressions calculated odds ratios for late-stage diagnosis and by race within tumor subtype. RESULTS: In total, 5,956 patients with Hodgkin lymphoma and 2,800 patients with RMS were included. Late-stage diagnosis of Hodgkin lymphoma was correlated with Black race [ORDistant(D) vs. regional/local (R&L) = 1.38 (1.13-1.68)], being uninsured [ORD vs. R&L = 1.38 (1.09-1.75)], and subtype [nodular sclerosis vs. Other Hodgkin lymphoma: ORD vs. R&L = 1.64 (1.34-2.01), Untyped: ORD vs. R&L = 1.30 (1.04-1.63)]. Late-stage RMS was correlated with bilingual households [ORDistant/regional(D&R) vs. local(L) = 2.66 (1.03-6.91)] and tumor type [alveolar vs. embryonal ORD vs. R&L = 6.16 (5.00-7.58)]. Community-level factors associated with late-stage Hodgkin lymphoma were greater Black (OR80-100% = 1.83; 95% CI = 1.11-3.02) and Hispanic (OR60-79% = 1.30; 95% CI = 1.05-1.60) dissimilarity indices. Late-stage diagnosis for RMS was associated with more redlined census tracts within counties (OR = 1.54; 95% CI = 1.02-2.35) and low/very low Child Opportunity Index (OR = 1.21; 95% CI = 1.02-1.45). CONCLUSIONS: Novel markers of community deprivation, such as redlining and racial segregation, were correlated with cancer outcomes for children with Hodgkin lymphoma and RMS in this first disparities study using Children's Oncology Group registries. IMPACT: The interplay of multilevel risk factors provides important consideration for efforts to improve early detection of pediatric cancer diagnosis.

A comparison of clinical profile and treatment outcome of Hodgkin's Lymphoma in Tanzania according to HIV status during the HAART era.

BACKGROUND: The incidence of Hodgkin's lymphoma (HL) in people living with HIV (PLWHA) and on HAART is approximately 20-30 times higher than in HIV-negative individuals. Most patients with HIV-HL present at an advanced stage (III-IV) have 'B' symptoms and extranodal involvement. The natural history and risk stratification of HIV-HL has undergone a significant change as a result of HAART's rollout. This study investigated the differences in clinicopathological and survival patterns of HL among individuals with and without HIV disease in Tanzania during the HAART era. METHODOLOGY: This hospital-based retrospective cohort study was conducted at the ORCI, Dar-Es-Salaam, Tanzania. Chi-square and Fisher's exact tests were used to compare proportions. The student t-test was used to compare means. To determine factors that predict survival, we used the log-rank test to analyze the variables in univariate analysis. A Cox regression model was used to analyze the significant factors from univariate analysis in multivariate analysis. RESULTS: Eighty-three patients with HL were recruited, and the prevalence of HIV-positive status was 27.7%. Most of the patients with HIV-HL had an age of > 30 years (73.9%), while most of the non-HIV-HL patients had an age of ≤ 30 years (63.3%) (P = 0.02). The 2-year OS rate for HIV-HL was 34%, while that for non-HIV-HL was 67%. Among the HIV-HL patients, predictors of a poorer outcome were a CD4 count ≤ 200 cells/mm3 (P = 0.05), lack of HAART use (P = 0.00), and the use of HAART for ≤ 10 months (P = 0.00). CONCLUSION: The prevalence of HIV-HL was 27.7% among HL patients. HIV positivity is still a poor prognostic factor in our setting, especially for patients not on HAART, on HAART for ≤ 10 months, or with a low CD4 count below 200 cells/mm3. Patients with HIV-HL were older and had higher LDH levels, whereas patients with non-HIV-HL were younger and had low LDH levels.

Presentation of B-cell lymphoma in childhood and adolescence: a systematic review and meta-analysis.

BACKGROUND: The diagnosis of B-cell lymphoma, one of the commonest cancers seen in childhood and adolescence, is challenging. There is a crucial need to identify and delineate the prevalence of associated symptoms in order to improve early diagnosis. AIMS: To identify clinical presentations associated with childhood and adolescent B-cell lymphomas and estimate symptom prevalence. METHODS: A systematic review of observational studies and meta-analysis of proportions was carried out. Medline and EMBASE were systematically searched, with no language restrictions, from inception to 1st August 2022. Observational studies with at least 10 participants, exploring clinical presentations of any childhood and adolescent lymphoma, were selected. Proportions from each study were inputted to determine the weighted average (pooled) proportion, through random-effects meta-analysis. RESULTS: Studies reported on symptoms, signs and presentation sites at diagnosis of 12,207 children and adolescents up to the age of 20. Hodgkin's lymphoma most frequently presented with adenopathy in the head-and-neck region (79% [95% CI 58%-91%]), whilst non-Hodgkin's lymphoma presented abdominally (55% [95% CI 43%-68%]). Symptoms associated with lymphoma included cervical lymphadenopathy (48% [95% CI 20%-77%]), peripheral lymphadenopathy (51% [95% CI 37%-66%]), B-symptoms (40% [95% CI 34%-44%]), fever (43% [95% CI 34%-54%]), abdominal mass (46% [95% CI 29%-64%]), weight loss (53% [95% CI 39%-66%]), head-and-neck mass (21% [95% CI 6%-47%]), organomegaly (29% [95% CI 23%-37%]), night sweats (19% [95% CI 10%-32%]), abdominal pain (28% [95% CI 15%-47%]), bone pain (17% [95% CI 10%-28%]) and abnormal neurology (11% [95% CI 3%-28%]). CONCLUSION: This systematic review and meta-analysis of proportions provides insight into the heterogeneous clinical presentations of B-cell lymphoma in childhood and adolescence and provides estimates of symptom prevalence. This information is likely to increase public and clinical awareness of lymphoma presentations and aid earlier diagnosis. This review further highlights the lack of studies exploring childhood and adolescent lymphoma presentations in primary care, where patients are likely to present at the earliest stages of their disease.

Characterizing age-related differences in Hodgkin lymphoma in children, adolescents and young adults.

Current studies describing younger children with Hodgkin lymphoma are limited by geographical region, small sample sizes and variable age groups. Although published data is lacking, there appears to be a trend toward a higher male to female ratio and a higher proportion of mixed cellularity subtype when compared to older cohorts. We performed a retrospective multicenter study utilizing the Pediatric Health Information System® database to evaluate patients aged 0-39 years with Hodgkin lymphoma. We identified 3,034 unique patients who met inclusion criteria. Younger age groups had a larger proportion of males, Hispanic/Latino ethnicity, and mixed cellularity subtype. Treatment-related complications, including mucositis, pain, bacterial infections, and thrombosis, were documented more frequently in older cohorts. We also found significant age-related differences in medical management. This study is the largest study evaluating age-related differences in patients with Hodgkin lymphomaand the first study to evaluate for differences in complicationsand supportive care management.

Pulmonary diseases in patients with classical Hodgkin lymphoma relative to a matched background population: A Danish national cohort study.

Late toxicities can impact survivorship in patients with classical Hodgkin lymphoma (cHL) with pulmonary toxicity after bleomycin-containing chemotherapy being a concern. The incidence of pulmonary diseases was examined in this Danish population-based study. A total of 1474 adult patients with cHL treated with ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) or BEACOPP (bleomycin, vincristine, etoposide, doxorubicin, cyclophosphamide, procarbazine and prednisone) between 2000 and 2018 were included along with 7370 age- and sex-matched comparators from the background population. Median follow-up was 8.6 years for the patients. Patients with cHL had increased risk of incident pulmonary diseases (HR 2.91 [95% CI 2.30-3.68]), with a 10-year cumulative risk of 7.4% versus 2.9% for comparators. Excess risks were observed for interstitial lung diseases (HR 15.84 [95% CI 9.35-26.84]) and chronic obstructive pulmonary disease (HR 1.99 [95% CI 1.43-2.76]), with a 10-year cumulative risk of 4.1% and 3.5% respectively for patients. No excess risk was observed for asthma (HR 0.82 [95% CI 0.43-1.56]). Risk factors for interstitial lung diseases were age ≥60 years, the presence of B-symptoms and low albumin. These findings document a significant burden of pulmonary diseases among patients with cHL and emphasize the importance of diagnostic work-up of pulmonary symptoms.

Thyroid abnormalities in patients with Hodgkin lymphoma: The importance of close surveillance.

INTRODUCTION: Survival in paediatric patients with Hodgkin lymphoma (HL) has increased over the last decades. However, these patients are at increased risk of developing late thyroid sequelae due to the treatment with irradiation and alkylating agents. METHODS: We conducted an observational and retrospective study in patients with a diagnosis of HL between 2007 and 2022, in a hospital that is a paediatric oncology reference centre, through the review of electronic health records. We collected data on demographic (age, sex), clinical, radiological and histopathological variables, the dosage of alkylating agents and radiotherapy (RT) and on thyroid disorders using Microsoft Excel. The data analysis was conducted with SPSS version 17, using the Fisher exact test for qualitative data, a nonparametric test for quantitative data and Kaplan-Meier curves. RESULTS: Sixty patients received a diagnosis of HL from 2007 to 2022. The median duration of follow-up was 78.5 months. There were 4 detected cases of hypothyroidism, 5 of thyroid nodules and 1 of subclinical hyperthyroidism. Treatment with RT was significantly associated with the development of hypothyroidism (P= .026), thyroid nodules (P= .01) and thyroid disease overall (P= .003). We estimated that the risk of thyroid disease increased 8-fold with each additional Grey received (hazard ratio, 1.081; 95% CI, 1.014-1.152; P= .017). CONCLUSION: Hodgkin lymphoma patients treated with RT are at increased risk of late thyroid disorders, mainly hypothyroidism and malignancy. This risk is greater the higher the RT dosage and the longer the follow-up. We did not find evidence of an association between the use of alkylating agents and an increase in the risk of thyroid disease.

Epidemiologic and Clinical Patterns of Malignant Lymphoma in Qatar 2013-2017: A Population-Based Cohort Study.

INTRODUCTION: Lymphoma, encompassing common non-Hodgkin lymphoma (NHL) and less common Hodgkin lymphoma (HL), represents significant hematological malignancies. Advancements in treatment modalities have reshaped survival rates, particularly in NHL. This complexity results in varying outcomes, some requiring extended observation periods and multiple chemotherapy treatments. The primary objective was to explore and compare the overall survival (OS) of HL and NHL at 1, 3, and 5-year follow-ups among adult lymphoma patients in Qatar during January 2013-December 2017. Further objectives encompass comparing the most prevalent histological types, clinical and epidemiological traits of HL and NHL, as well as secondary aims of assessing clinical features, treatment, response, disease-free survival, and OS. METHODS: A retrospective, descriptive study of consecutive cases was conducted at Qatar's NCCCR between 2013 and 2017. Inclusion criteria involved patients ≥18 years old, of any gender and clinical stage at diagnosis, who received chemotherapy and had known outcomes. Descriptive statistics were applied, and survival analysis utilized Kaplan-Meier curves. STATA version 13.0 facilitated data analysis. RESULTS: Between 2013 and 2017, 414 individuals in Qatar were diagnosed with lymphoma. The median age at diagnosis was 49 years (IQR 36-95 years; p < 0.001) across all patients. Males exhibited a higher likelihood of developing HL and NHL, comprising 74% and 70% of cases, respectively, though this difference was statistically insignificant (p = 0.45). Among NHL-B subtypes, mature B-cell neoplasms (60%) predominated, while lymphocyte-rich subtype (49%) was prominent in HL cases. With a median follow-up of 17.3 months, OS rates at 1, 3, and 5 years were 99%, 82%, and 64%, respectively for all lymphoma patients. Subtype stratification revealed trends in 3-year follow-up OS (94 vs. 82%) for HL and NHL, with 5-year OS of 67% and 60%, respectively. HL demonstrated higher OS throughout the study period compared to NHL (p < 0.001), though median OS remained unreached. CONCLUSIONS: Diffuse large B-cell lymphoma emerged as the most prevalent subtype among lymphomas in Qatar. Generally, HL exhibited superior survival rates, at 67% compared to 60% for NHL. Minor deflation in survival rates, particularly for HL, might be attributed to Qatar's immigration patterns.

Doxorubicin Exposure and Breast Cancer Risk in Survivors of Adolescent and Adult Hodgkin Lymphoma.

PURPOSE: Female Hodgkin lymphoma (HL) survivors treated with chest radiotherapy (RT) at a young age have a strongly increased risk of breast cancer (BC). Studies in childhood cancer survivors have shown that doxorubicin exposure may also increase BC risk. Although doxorubicin is the cornerstone of HL chemotherapy, the association between doxorubicin and BC risk has not been examined in HL survivors treated at adult ages. METHODS: We assessed BC risk in a cohort of 1,964 female 5-year HL survivors, treated at age 15-50 years in 20 Dutch hospitals between 1975 and 2008. We calculated standardized incidence ratios, absolute excess risks, and cumulative incidences. Doxorubicin exposure was analyzed using multivariable Cox regression analyses. RESULTS: After a median follow-up of 21.6 years (IQR, 15.8-27.1 years), 252 women had developed invasive BC or ductal carcinoma in situ. The 30-year cumulative incidence was 20.8% (95% CI, 18.2 to 23.4). Survivors treated with a cumulative doxorubicin dose of >200 mg/m2 had a 1.5-fold increased BC risk (95% CI, 1.08 to 2.1), compared with survivors not treated with doxorubicin. BC risk increased 1.18-fold (95% CI, 1.05 to 1.32) per additional 100 mg/m2 doxorubicin (Ptrend = .004). The risk increase associated with doxorubicin (yes v no) was not modified by age at first treatment (hazard ratio [HR]age <21 years, 1.5 [95% CI, 0.9 to 2.6]; HRage ≥21 years, 1.3 [95% CI, 0.9 to 1.9) or chest RT (HRwithout mantle/axillary field RT, 1.9 [95% CI, 1.06 to 3.3]; HRwith mantle/axillary field RT, 1.2 [95% CI, 0.8 to 1.8]). CONCLUSION: This study shows that treatment with doxorubicin is associated with increased BC risk in both adolescent and adult HL survivors. Our results have implications for BC surveillance guidelines for HL survivors and treatment strategies for patients with newly diagnosed HL.

Similar geographic distribution of mortality from multiple sclerosis, Hodgkin lymphoma, and inflammatory bowel disease in the United States.

BACKGROUND: Previous epidemiologic studies have suggested a linkage between the occurrence of multiple sclerosis (MS), Hodgkin lymphoma (HL), Crohn's disease (CD), and ulcerative colitis (UC). It was hypothesized that the 4 diagnoses would be characterized by similar geographic distributions within the United States. AIMS: To compare the US geographic distributions of these 4 diagnoses in a cross-sectional study. METHODS: Using the US vital statistics, state-specific death rates and age-specific proportional mortality ratios (PMR) were calculated for each diagnosis. Similarities in the geographic distributions of the 4 diagnoses were tested by linear and Poisson regression analyses. The PMR values from different states were correlated among pairs of consecutive age-groups. RESULTS: The 6 linear correlation coefficients (r) among the geographic distributions of the 4 diseases were as follows: HL vs. MS (r = 0.28), HL vs. CD (r = 0.74), HL vs. UC (r = 0.64); MS vs. CD (r = 0.18), MS vs. UC (r = 0.66); CD vs. UC (r = 0.58). Using Poisson regression, the geographic distributions of MS, HL, CD, and UC were all found to be significantly correlated with each other. In MS, significant correlations between the PMR values of each two consecutive age-groups started with the age-group 25-44 years. In HL, such significant correlations started at age 10-14, in CD at age 20-24, and in UC at age 20-24 years. CONCLUSIONS: Within the United States, mortality from MS, HL, CD, and UC are characterized by similar geographic distributions. The environmental influences responsible for these resembling geographic distributions start exerting their influence during early lifetime.

Epidemiology of pediatric hematological malignancies in Kazakhstan: Data from Unified National Electronic Healthcare System 2014-2021.

We aimed to describe incidence and all-cause mortality of hematological pediatric malignancies (leukemia and lymphomas) in Kazakhstan based on nationwide large-scale healthcare data from the Unified National Electronic Healthcare System (UNEHS) for the 2014-2021 year period. The cohort included data of patients less than 18 years old with the diagnosis of hematological malignancies registered in the UNEHS (inpatient and outpatient registries) for the year period 2014-2021. Descriptive statistics were conducted to indicate socio-demographic characteristics of the cohort. Incidence and all-cause mortality were calculated per 100,000 population. Cox proportional hazard regression analysis was performed to investigate the association between determinants with the all-cause mortality. The total cohort consisted of 3357 children with leukemia and 1474 children with lymphomas. The mean age at diagnosis of leukemia and lymphomas was 7.3 ± 4.7 and 9.9 ± 4.9 years, respectively. The incidence rate of hematological malignancies was 6.8 per 100,000 in 2021. Patients with ALL had a higher incidence rate than patients with AML (3.4 and 1.2 per 100,000 in 2021, respectively). The incidence rate of HL and NHL was relatively similar which varied from 0.6 to 2.6 per 100,000 in 2014-2021. All-cause mortality of pediatric hematological malignancies varied from 1.1 to 1.5 per 100,000 in 2014-2021, with the peak in 2016 (1.7 per 100,000). Younger age is significantly associated with increased risk of all-cause mortality in children with AML. CONCUSION: Patients with ALL had a higher incidence rate than patients with AML. The incidence rate of HL and NHL was relatively similar. All-cause mortality rates for leukemia and lymphomas were quite stable during the study period. Younger age is significantly associated with increased all-cause mortality among AML patients. However, there is no significant association of age with all-cause mortality among ALL, HL and NHL. In order to obtain more reliable data and analysis on pediatric (hematological) malignancies, specific registries for childhood tumors (including detailed information on relapses, treatments, short and long-term side effects, and specific death causes) should be implemented. WHAT IS KNOWN: • Leukemias and lymphomas together account for around 45% of all pediatric malignancies. • Lymphoma accounts for 12% of all childhood malignancies; non-Hodgkin's lymphomas (NHL) are more frequent than Hodgkin's lymphomas (HL). WHAT IS NEW: • The incidence rate of ALL was higher than the incidence rate of AML throughout the whole study period, whereas all-cause mortality of ALL and AML was quite stable. • According to Cox PH analysis, younger age (0-5 years old) was associated with a higher risk of death among AML children compared to older children, and no significant association of age was observed with all-cause mortality among ALL and lymphomas.

Lifetime risks of second primary malignancies after pediatric Hodgkin lymphoma and non-Hodgkin lymphoma.

OBJECTIVES: Survivors after pediatric Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) are with lifetime risk for second primary malignancy (SPM). This necessitates a thorough analysis to better understand the potential long-term health implications for these individuals. METHODS: We used a US-wide population-based cancer registry data to quantify the SPM risk and identify its incidence patterns among pediatric lymphoma patients. RESULTS: We observed 4.74-fold (95% CI 4.27-5.25) and 3.40-fold (95% CI 2.78-4.10) increased risks of SPM in survivors after pediatric HL and NHL, respectively. Through over 40 years' follow-up, the cumulative incidence of SPM for pediatric lymphoma was persistently increasing, and here we firstly report the high 40-year cumulative incidence rates of SPM, 22.2% for HL and 12.6% for NHL, suggesting that SPM accounts for a great proportion of deaths among survivors. Of 6805 pediatric lymphomas, 462 (6.36%) developed a SPM, especially second breast and thyroid cancer, followed by hematologic neoplasms including leukemia and NHL. The competing risk analysis demonstrated gender, lymphoma subtype and radiotherapy were significantly associated with SPM. Different risk patterns of SPM were identified between pediatric HL and NHL. Chemotherapy accelerated SPM development but did not increase its incidence risk. CONCLUSION: Overall, patients after pediatric lymphoma can be with high lifetime risk of SPM, and more attention should be paid to SPM-related signs for early detection and intervention.

Late Cardiac Toxic Effects Associated With Treatment Protocols for Hodgkin Lymphoma in Children.

Importance: Contemporary North American trials for children with Hodgkin lymphoma (HL) have decreased radiation therapy (RT) use and increased pharmacologic cardioprotection but also increased the cumulative doxorubicin dose, making overall treatment consequences for late cardiac toxic effects uncertain. Objective: To estimate the risk of cardiac toxic effects associated with treatments used in modern pediatric HL clinical trials. Design, Setting, and Participants: For this cohort study, Fine and Gray models were fitted using survivors in the Childhood Cancer Survivor Study who were diagnosed with HL between January 1, 1970, and December 31, 1999, and were followed for a median of 23.5 (range, 5.0-46.3) years. These models were applied to the exposures in the study population to estimate the 30-year cumulative incidence of cardiac disease. The study population comprised patients with intermediate-risk or high-risk HL treated in 4 consecutive Children's Oncology Group clinical trials from September 2002 to October 2022: AHOD0031, AHOD0831, AHOD1331, and S1826. Data analysis was performed from April 2020 to February 2023. Exposures: All patients received chemotherapy including doxorubicin, and some patients received mediastinal RT, dexrazoxane, or mediastinal RT and dexrazoxane. Main Outcomes and Measures: Estimated 30-year cumulative incidence of grade 3 to 5 cardiac disease. Results: The study cohort comprised 2563 patients, with a median age at diagnosis of 15 (range, 1-22) years. More than half of the patients were male (1357 [52.9%]). All 2563 patients received doxorubicin, 1362 patients (53.1%) received mediastinal RT, and 307 patients (12.0%) received dexrazoxane. Radiation therapy use and the median mean heart dose among patients receiving RT decreased, whereas the planned cumulative dose of doxorubicin and use of dexrazoxane cardioprotection increased. For patients treated at age 15 years, the estimated 30-year cumulative incidence of severe or fatal cardiac disease was 9.6% (95% CI, 4.2%-16.4%) in the AHOD0031 standard treatment group (enrolled 2002-2009), 8.6% (95% CI, 3.8%-14.9%) in the AHOD0831 trial (enrolled 2009-2012), 8.2% (95% CI, 3.6%-14.3%) in the AHOD1331 trial (enrolled 2015-2019), and 6.2% (95% CI, 2.7%-10.9%) in the S1826 trial (enrolled 2019-2022), whereas the expected rate in an untreated population was 5.0% (95% CI, 2.1%-9.3%). Despite the estimated reduction in late cardiac morbidity, the frequency of recommended echocardiographic screening among survivors will increase based on current guidelines. Conclusions and Relevance: In this cohort study of sequential HL trials, reductions in the proportion of children receiving mediastinal RT and increases in dexrazoxane use were estimated to offset the increased doxorubicin dose and produce a net reduction in late cardiac disease. Further studies on dexrazoxane are warranted to confirm whether its role in reducing cardiac toxic effects is maintained long term. These findings suggest that survivorship follow-up guidelines should be refined to align with the risks associated with treatment.

Men treated with BEACOPP for Hodgkin lymphoma may be at increased risk of testosterone deficiency.

In the current study, we report the prevalence of male testosterone deficiency in a cohort of 60 male long-term survivors of malignant lymphoma with normal total testosterone but in the lower part of the reference level. Testosterone deficiency was defined as subnormal concentrations of total testosterone or subnormal concentrations of calculated free testosterone. The aim was to clarify whether total testosterone was sufficient for identification of testosterone deficiency in male survivors of malignant lymphoma. Hormonal analyses taken at follow-up were compared with samples taken at diagnosis for a subgroup of 20 survivors, for evaluation of changes in hormones over time. Another group of 83 similar survivors of malignant lymphoma with testosterone in the high end of reference levels were also used for comparison, to identify groups of increased risk of testosterone deficiency. A total group of 143 survivors were therefore included in the study. Our findings indicate that for screening purposes an initial total testosterone is sufficient in some survivors because sexual hormone binding globulin concentration was found stable over time. However, 15% were found with subnormal calculated free testosterone. Survivors intensely treated for Hodgkin lymphoma and older survivors were identified as high-risk groups for testosterone deficiency necessitating endocrinological attention during follow-up. Some evidence of pituitary downregulation was also found, because of uncompensated decreases in testosterone concentration over time. In conclusion, longitudinal measurements of total testosterone alone do not seem adequate for the screening of testosterone deficiency for all long-term lymphoma survivors.

Role of non-chromosomal birth defects on the risk of developing childhood Hodgkin lymphoma: A Children's Oncology Group study.

BACKGROUND: Non-chromosomal birth defects are an important risk factor for several childhood cancers. However, these associations are less clear for Hodgkin lymphoma (HL). Therefore, we sought to more fully elucidate the association between non-chromosomal birth defects and HL risk. PROCEDURE: Information on cases (n = 517) diagnosed with HL (ages of 0-14) at Children's Oncology Group Institutions for the period of 1989-2003 was obtained. Control children without a history of cancer (n = 784) were identified using random digit dialing and individually matched to cases on sex, race/ethnicity, age, and geographic location. Parents completed comprehensive interviews and answered questions including whether their child had been born with a non-chromosomal birth defect. To test the association between birth defects and HL risk, conditional logistic regression was applied to generate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). RESULTS: Children born with any non-chromosomal birth defect were not more likely to be diagnosed with HL at 0-14 years of age (aOR: 0.91; 95% CI: 0.69-1.21). No associations were detected between major or minor birth defects and HL (aOR: 1.34; 95% CI: 0.67-2.67 and aOR: 0.88; 95% CI: 0.57-1.34, respectively). Similarly, no association was observed for children born with any birth defect and EBV-positive HL (aOR: 0.57; 95% CI: 0.25-1.26). CONCLUSIONS: Previous assessments of HL in children with non-chromosomal birth defects have been limited. Using data from the largest case-control study of HL in those <15 years of age, we did not observe strong associations between being born with a birth defect and HL risk.

Concurrence of inflammatory bowel disease with multiple sclerosis or Hodgkin lymphoma.

BACKGROUND AND AIMS: Epidemiologic evidence suggests that Hodgkin lymphoma (HL) and multiple sclerosis (MS) share a common set of risk factors with Crohn's disease (CD) and ulcerative colitis (UC). It was hypothesized that such shared risk factors would lead to clustering of the 4 diagnoses in the same patients. METHODS: All patients with HL, MS, CD, or UC were identified in the veterans population from 2016-2020 and the Medicare population from 1986 to 1989. In a case-control study, the observed concurrences amongst these 4 diagnoses were compared with their expected frequencies in the overall veterans or Medicare population during the same time period by calculating odds ratios (OR) with their 95% confidence intervals (CI). RESULTS: The study included 6 million veterans and 35 million Medicare patients. In the veterans population, inflammatory bowel disease (IBD) was significantly associated with a concurrent diagnosis of HL (OR: 1.40, 95% CI: 1.15-1.71) and MS (1.34, 1.19-1.50). In the Medicare population, IBD was also significantly associated with HL (1.84, 1.07-3.17) and MS (2.31, 1.59-3.35). Similar trends were observed in CD or UC when analyzed separately in both datasets. In the veterans population, adjustment for the potentially confounding influence of ethnicity, sex, and age left all OR values largely unaffected and statistically significant. CONCLUSION: The concurrence of IBD with HL or MS could reflect on a common pathway in the etiology or pathogenesis of these 4 diseases.