Project description:PurposeHodgkin lymphoma (HL) survivors experience high risks of second cancers and cardiovascular disease, but no studies have considered whether the occurrence of these and other medical conditions differ by sociodemographic factors in adolescent and young adult (AYA) survivors.MethodsData for 5,085 patients aged 15-39 when diagnosed with HL during 1996-2012 and surviving ≥ 2 years were obtained from the California Cancer Registry and linked to hospitalization data. We examined the impact of race/ethnicity, neighborhood socioeconomic status (SES), and health insurance on the occurrence of medical conditions (≥ 2 years after diagnosis) and the impact of medical conditions on survival using multivariable Cox proportional hazards regression.ResultsTwenty-six percent of AYAs experienced at least one medical condition and 15% had ≥ 2 medical conditions after treatment for HL. In multivariable analyses, Black HL survivors had a higher likelihood (vs. non-Hispanic Whites) of endocrine [hazard ratio (HR) = 1.37, 95% confidence interval (CI) 1.05-1.78] and circulatory system diseases (HR = 1.58, CI 1.17-2.14); Hispanics had a higher likelihood of endocrine diseases [HR = 1.24 (1.04-1.48)]. AYAs with public or no insurance (vs. private/military) had higher likelihood of circulatory system diseases, respiratory system diseases, chronic kidney disease/renal failure, liver disease, and endocrine diseases. AYAs residing in low SES neighborhoods (vs. high) had higher likelihood of respiratory system and endocrine diseases. AYAs with these medical conditions or second cancers had an over twofold increased risk of death.ConclusionStrategies to improve health care utilization for surveillance and secondary prevention among AYA HL survivors at increased risk of medical conditions may improve outcomes.
Project description:The 6th International Symposium on Childhood, Adolescent and Young Adult (CAYA) Non-Hodgkin Lymphoma (NHL) was held in Rotterdam, Netherlands, 26-29 September, 2018. This summary manuscript is a perspective on the presentations from the plenary scientific sessions, including wellness and survivorship, B-cell NHL, AYA lymphoma, translational NHL biology, lymphoma immunology, bone marrow transplantation and cell therapy, T/Natural Killer cell lymphoma, anaplastic large cell lymphoma, lymphoblastic lymphoma, novel lymphoma therapeutics and Hodgkin lymphoma. The symposium was attended by over 260 registrants from 42 different countries and included young, middle and senior investigators. Finally, the Angelo Rosolen, MD, Memorial Lecture was delivered by Alfred Reiter, MD.
Project description:BackgroundAdolescent and young adults (AYA) represent one third of patients affected by Hodgkin lymphoma (HL). These patients are frequently treated either with pediatric or adult protocol depending on their physician background. This population has been understudied so far, in terms of HL characteristics and treatment-associated outcomes.AimWe aimed to extensively describe HL features in the AYA population including HL characteristics, progression-free (PFS) and overall survival (OS).MethodsFrom 1979 to 2013, consecutive patients with HL aged between 15 to 25 years and followed at Saint-Louis Hospital were prospectively enrolled. Survivals were estimated using the Kaplan-Meier method.Results349 patients were included and studied, with a median follow-up of 7 years. The majority of patients were treated with adult protocols (mainly ABVD and BEACOPP). They presented adverse clinical characteristics with a high proportion of stage III and IV according to Ann Arbor classification (45 %), a high rate of B symptoms (46 %) and extra-nodal involvement (36 %). Despite these pejorative clinical features, the prognosis remains good with a 10-year PFS and OS estimated at 81.0 % (95%CI [76.7-85.5]) and 90.7% (95%CI [87.2-94.4]), respectively. In multivariate analysis, stages III and IV according to Ann Arbor classification, mixed cellularity histology, elevated neutrophils and LDH above range were independently associated with a worse PFS. We identified a subgroup of 11 primary refractory patients with a particularly poor prognosis. The toxicity rate was low (7.4 %).ConclusionDespite their baseline pejorative features, AYA with HL have a good prognosis. Progresses are still needed in order to reduce toxicities. Primary refractory patients with a particularly poor prognosis should be detected early in order to quickly introduce new targeted therapies.
Project description:Hodgkin lymphoma (HL) is a common adolescent and young adult (AYA) cancer. While outcome disparities between pediatric vs. adult centers [locus of care (LOC)] have been demonstrated in other AYA cancers such as acute lymphoblastic leukemia, they have not been well studied in HL. We therefore compared population-based treatment patterns and outcomes in AYA HL by LOC. The IMPACT Cohort includes data on all Ontario, Canada AYA (15-21 years) diagnosed with HL between 1992 and 2012. Linkage to population-based health administrative data identified late effects. We examined LOC-based differences in treatment modalities, cumulative doses, event-free survival (EFS), overall survival (OS), and late effects. Among 954 AYA, 711 (74.5%) received therapy at adult centers. Pediatric center AYA experienced higher rates of radiation therapy but lower cumulative doses of doxorubicin and bleomycin. 10-year EFS did not differ between pediatric vs. adult cancer vs. community centers (83.8% ± 2.4% vs. 82.8% ± 1.6% vs. 82.7%±3.0%; P = .71); LOC was not significantly associated with either EFS or OS in multivariable analyses. Higher incidences of second malignancies in pediatric center AYA and of cardiovascular events in adult center AYA were observed, but were not significant. In conclusion, while pediatric and adult centers used different treatment strategies, outcomes were equivalent. Differences in treatment exposures are however likely to result in different late-effect risks. Protocol choice should be guided by individual late-effect risk.
Project description:The non-Hodgkin lymphomas (NHLs) occurring in children and adolescents and young adults (AYA) are characterized by various age-related differences in tumor biology and survival. Children generally present with high-grade lymphomas, such as Burkitt lymphoma, diffuse large B-cell lymphoma, lymphoblastic lymphoma, and anaplastic large cell lymphoma, whereas low-grade histologic subtypes, such as follicular lymphoma, occur more frequently with increasing age. Treatment outcome for children with NHL is generally superior to that observed in adults. Factors contributing to this discrepancy include psychosocial factors, patient factors, and differences in tumor biology and therapy. These factors will be reviewed, with particular attention to the biological features of diffuse large B-cell lymphoma and anaplastic large cell lymphoma and corresponding therapeutic challenges. Novel targeting agents have been developed, which have been shown to be active in some patients. There is clearly a need for treatment protocols with eligibility criteria that cover the full span of the pediatric and AYA age range and that incorporate detailed molecular characterization of the tumors.
Project description:BackgroundOwing to a growing number of young and adolescent Hodgkin lymphoma (HL) survivors, awareness of (long-term) adverse effects of anticancer treatment increases. The risk of impaired reproductive ability is of great concern given its impact on quality of life. There is currently no review available on fertility after childhood HL treatment.Objective and rationaleThe aim of this narrative review was to summarize existing literature on different aspects of reproductive function in male and female childhood, adolescent, and young adult HL survivors.Search methodsPubMed and EMBASE were searched for articles evaluating fertility in both male and female HL survivors aged <25 years at diagnosis. In females, anti-Müllerian hormone (AMH), antral follicle count, premature ovarian insufficiency (POI), acute ovarian failure, menstrual cycle, FSH, and pregnancy/live births were evaluated. In males, semen-analysis, serum FSH, inhibin B, LH, testosterone, and reports on pregnancy/live births were included. There was profound heterogeneity among studies and a lack of control groups; therefore, no meta-analyses could be performed. Results were presented descriptively and the quality of studies was not assessed individually.OutcomesAfter screening, 75 articles reporting on reproductive markers in childhood or adolescent HL survivors were included. Forty-one papers reported on 5057 female HL survivors. The incidence of POI was 6-34% (median 9%; seven studies). Signs of diminished ovarian reserve or impaired ovarian function were frequently seen (low AMH 55-59%; median 57%; two studies. elevated FSH 17-100%; median 53%; seven studies). Most survivors had regular menstrual cycles. Fifty-one studies assessed fertility in 1903 male HL survivors. Post-treatment azoospermia was highly prevalent (33-100%; median 75%; 29 studies). Long-term follow-up data were limited, but reports on recovery of semen up to 12 years post-treatment exist. FSH levels were often elevated with low inhibin B (elevated FSH 0-100%; median 51.5%; 26 studies. low inhibin B 19-50%; median 45%; three studies). LH and testosterone levels were less evidently affected (elevated LH 0-57%, median 17%; 21 studies and low testosterone 0-43%; median 6%; 15 studies). In both sexes, impaired reproductive ability was associated with a higher dose of cumulative chemotherapeutic agents and pelvic radiotherapy. The presence of abnormal markers before treatment indicated that the disease itself may also negatively affect reproductive function (Females: AMH<p10 9%; one study and Males: azoospermia 0-50%; median 10%; six studies). Reports on chance to achieve pregnancy during survivorship are reassuring, although studies had their limitations and the results are difficult to evaluate. In the end, a diminished ovarian reserve does not exclude the chance of a live birth, and males with aberrant markers may still be able to conceive.Wider implicationsThis review substantiates the negative effect of HL treatment on gonadal function and therefore young HL survivors should be counseled regarding their future reproductive life, and fertility preservation should be considered. The current level of evidence is insufficient and additional trials on the effects of HL and (current) treatment regimens on reproductive function are needed. In this review, we make a recommendation on reproductive markers that could be assessed and the timing of (repeated) measurements.
Project description:Cancers cause significant mortality and morbidity in adolescents and young adults (AYAs), but their biological underpinnings are incompletely understood. Here, we analyze clinical and genomic disparities between AYAs and older adults (OAs) in more than 100,000 cancer patients. We find significant differences in clinical presentation between AYAs and OAs, including sex, metastasis rates, race and ethnicity, and cancer histology. In most cancer types, AYA tumors show lower mutation burden and less genome instability. Accordingly, most cancer genes show less mutations and copy number changes in AYAs, including the noncoding TERT promoter mutations. However, CTNNB1 and BRAF mutations are consistently overrepresented in AYAs across multiple cancer types. AYA tumors also exhibit more driver gene fusions that are frequently observed in pediatric cancers. We find that histology is an important contributor to genetic disparities between AYAs and OAs. Mutational signature analysis of hypermutators shows stronger endogenous mutational processes such as MMR-deficiency but weaker exogenous processes such as tobacco exposure in AYAs. Finally, we demonstrate a panoramic view of clinically actionable genetic events in AYA tumors. The biological underpinnings underlying the increased mortality and morbidity in adolescents and young adults (AYA) remains poorly understood. Here, the authors investigate the clinical and genomic disparities in AYA and older adults in a cohort of more than 100,000 cancer patients.
Project description:Outcomes in older adults with classic Hodgkin lymphoma (cHL) have traditionally been poor, in part, related to poor tolerance to standard chemotherapy. Herein, we evaluated the survival of patients with cHL aged ≥60 years in British Columbia in a population-based analysis. From 1961 to 2019, 744 patients with newly diagnosed cHL were identified. With a median follow-up of 9 years, 5-year disease-specific survival (DSS) and overall survival (OS) have improved by decade comparison (both P < .001), remaining stable in the past 20 years (DSS, P = .35; OS, P = .26). In the modern management era (2000-present), 361 of 401 patients (90%) received active therapy for cHL and had a 5-year OS of 60%. For those who received curative-intent therapy (n = 327), the 5-year progression-free survival (PFS), OS, and DSS were 60%, 65%, and 76%, respectively, and estimates were superior in those who were 60 to 69 years of age (72%, 77%, and 83%, respectively) compared with those who were 70 to 79 years of age (54%, 57%, and 70%, respectively) and ≥80 years of age (28%, 39%, and 63%, respectively) (P < .05 for all). Overall, pulmonary toxicity occurred in 58 of 279 patients (21%) treated with bleomycin, with 22 of 58 (38%) occurring after cycles 1 or 2, accounting for 8 of 20 (40%) treatment-related deaths. Outcomes in older adults with cHL have improved in recent decades; however, they remain poor for those aged ≥70 years, even in the modern treatment era. Furthermore, treatment-related toxicity remains a significant concern and use of bleomycin should be avoided in most patients.
Project description:BackgroundAdolescent/young adult Hodgkin lymphoma (AYAHL) survivors report fewer exposures to infections during childhood compared with controls, and they have functional lymphocyte aberrations. The gut microbiota plays a central role in immunity.MethodsWe investigated whether fecal microbial diversity differed between 13 AYAHL survivors and their unaffected co-twin controls. Pyrosequencing of fecal bacterial 16S rRNA amplicons yielded 252?943 edited reads that were assigned to species-level operational taxonomic units (OTUs) and standardised for sequencing depth by random sampling. Microbial diversity was compared within vs between twin pairs and by case-control status.ResultsThe number of unique OTUs was more similar within twin pairs compared with randomly paired participants (P=0.0004). The AYAHL cases had fewer unique OTUs compared with their co-twin controls (338 vs 369, P=0.015); this difference was not significant (169 vs 183, P=0.10) when restricted to abundant OTUs.ConclusionIn this small study, AYAHL survivors appear to have a deficit of rare gut microbes. Further work is needed to determine if reduced microbial diversity is a consequence of the disease, its treatment, or a particularly hygienic environment.
Project description:BackgroundHodgkin lymphoma (HL) is a treatable tumor affecting children, adolescents and young adults (AYAs; 15-39 years old). Population-based studies report worse survival for non-White children and AYAs but have limited data on individual therapeutic exposures. This study examined overall and HL-specific survival in a population-based cohort of patients while adjusting for sociodemographic factors and treatment.MethodsData for 4807 patients younger than 40 years with HL (2007-2017) were obtained from the California Cancer Registry. Individual treatment information was extracted from text fields; chemotherapy regimens were defined by standard approaches for pediatric and adult HL. Multivariable Cox models examined the influence of patient and treatment factors on survival.ResultsAt a median follow-up of 4.4 years, 95% of the patients were alive. Chemotherapy differed by age, with 70% of 22- to 39-year-olds and 41% of <22-year-olds receiving doxorubicin, bleomycin, vinblastine, and dacarbazine (P < .001). In multivariable models, older patients (22-39 vs < 21 y; hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.11-2.10), Black (vs White patients); HR, 1.90; 95% CI, 1.25-2.88), and Hispanic patients (HR, 1.45; 95% CI, 1.06-1.99) experienced worse survival; among those < 21 y, Black race was associated with a 3.3-fold increased risk of death (HR, 3.26; 95% CI, 1.43-7.42).ConclusionsIn children and AYAs with HL, older age and non-White race/ethnicity predicted worse survival after adjustments for treatment data. Further work is needed to identify the biological and nonbiological factors driving disparities in these at-risk populations.