| 1. |
- Englund, Annika, et al.
(author)
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Hodgkin lymphoma in children, adolescents and young adults - a comparative study of clinical presentation and treatment outcome.
- 2018
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In: Acta Oncologica. - 0284-186X .- 1651-226X. ; 57:2, s. 276-282
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Journal article (peer-reviewed)abstract
- 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.
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| 4. |
- Glimelius, Ingrid, 1975-, et al.
(author)
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Distribution of hospital care among pediatric and young adult Hodgkin lymphoma survivors : A population-based cohort study from Sweden and Denmark
- 2019
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In: Cancer Medicine. - : Wiley. - 2045-7634. ; 8:10, s. 4918-4927
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Journal article (peer-reviewed)abstract
- 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.
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| 5. |
- Hollander, Peter, et al.
(author)
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High proportions of PD-1+ and PD-L1+ leukocytes in classical Hodgkin lymphoma microenvironment are associated with inferior outcome
- 2017
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In: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 1:18, s. 1427-1439
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Journal article (peer-reviewed)abstract
- Immune checkpoint inhibition targeting the programmed death receptor (PD)-1 pathway is a novel treatment approach in relapsed and refractory classical Hodgkin lymphoma (cHL). Identifying patients with a high risk of treatment failure could support the use of PD-1 inhibitors as front-line treatment. Our aim was to investigate the prognostic impact of PD-1, programmed death-ligand 1 (PD-L1), and PD-L2 in the tumor microenvironment in diagnostic biopsies of patients with cHL. Patients from Denmark and Sweden, diagnosed between 1990 and 2007 and ages 15 to 86 years, were included. Tissue microarray samples were available from 387 patients. Immunohistochemistry was used to detect PD-1, PD-L1, and PD-L2, and the proportions of positive cells were calculated. Event-free survival (EFS; time to treatment failure) and overall survival (OS) were analyzed using Cox proportional hazards regression. High proportions of both PD-1(+) (hazard ratio [HR], 1.77; 95% confidence interval [CI], 1.10-2.86) and PD-L1(+) (HR 5 1.89; 95% CI, 1.08-3.30) leukocytes in the microenvironment were associated with inferior EFS in a multivariate analysis (adjusted for white blood cell count >15 x 10(9)/L, hemoglobin <105 g/L, albumin <40 g/L, B symptoms, extranodal involvement, stage, bulky tumor, nodular sclerosis subtype, Epstein-Barr virus status, lymphocyte count <0.6 x 10(9)/L, sex, and country). A high proportion of PD-L1(+) leukocytes was also associated with inferior OS in a multivariate analysis (HR, 3.46; 95% CI, 1.15-10.37). This is the first study to show a correlation after multivariate analysis between inferior outcome in cHL and a high proportion of both PD-1(+) and PD-L1(+) leukocytes in the tumor microenvironment.
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| 6. |
- Pedersen, Mette A., et al.
(author)
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Focal skeletal FDG uptake indicates poor prognosis in cHL regardless of extent and first-line chemotherapy
- 2019
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In: British Journal of Haematology. - : WILEY. - 0007-1048 .- 1365-2141. ; 186:3, s. 431-439
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Journal article (peer-reviewed)abstract
- F-18-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) is used for staging classical Hodgkin lymphoma (cHL) with high sensitivity for skeletal involvement. However, it is unclear whether a single bone lesion carries the same adverse prognosis as multifocal lesions and if this is affected by type of chemotherapy [ABVD (adriamycin, bleomycin, vincristine, dacarbazine) versus BEACOPP (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, prednisone)]. We reviewed the clinico-pathological and outcome data from 209 patients with newly diagnosed cHL staged by FDG-PET/CT. Patterns of skeletal/bone marrow uptake (BMU) were divided into 'low' and 'high' diffuse BMU (i.e. without focal lesions), and unifocal or multifocal lesions. Additional separate survival analysis was performed, taking type of chemotherapy into account. Forty patients (19 center dot 2%) had skeletal lesions (20 unifocal, 20 multifocal). The 3-year progression-free-survival (PFS) was 80% for patients with 'low BMU', 87% for 'high BMU', 69% for 'unifocal' and 51% for 'multifocal' lesions; median follow-up was 38 months. The presence of bone lesions, both uni- and multifocal, was associated with significantly inferior PFS (log rank P = 0 center dot 0001), independent of chemotherapy type. Thus, increased diffuse BMU should not be considered as a risk factor in cHL, whereas unifocal or multifocal bone lesions should be regarded as important predictors of adverse outcome, irrespective of the chemotherapy regimen used.
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- Jorgensen, Rasmus Rask Kragh, et al.
(author)
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Machine Learning-Based Survival Prediction Models for Progression-Free and Overall Survival in Advanced-Stage Hodgkin Lymphoma
- 2024
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In: JCO Clinical Cancer Informatics. - : Lippincott Williams & Wilkins. - 2473-4276. ; 8
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Journal article (peer-reviewed)abstract
- PurposePatients diagnosed with advanced-stage Hodgkin lymphoma (aHL) have historically been risk-stratified using the International Prognostic Score (IPS). This study investigated if a machine learning (ML) approach could outperform existing models when it comes to predicting overall survival (OS) and progression-free survival (PFS).Patients and MethodsThis study used patient data from the Danish National Lymphoma Register for model development (development cohort). The ML model was developed using stacking, which combines several predictive survival models (Cox proportional hazard, flexible parametric model, IPS, principal component, penalized regression) into a single model, and was compared with two versions of IPS (IPS-3 and IPS-7) and the newly developed aHL international prognostic index (A-HIPI). Internal model validation was performed using nested cross-validation, and external validation was performed using patient data from the Swedish Lymphoma Register and Cancer Registry of Norway (validation cohort).ResultsIn total, 707 and 760 patients with aHL were included in the development and validation cohorts, respectively. Examining model performance for OS in the development cohort, the concordance index (C-index) for the ML model, IPS-7, IPS-3, and A-HIPI was found to be 0.789, 0.608, 0.650, and 0.768, respectively. The corresponding estimates in the validation cohort were 0.749, 0.700, 0.663, and 0.741. For PFS, the ML model achieved the highest C-index in both cohorts (0.665 in the development cohort and 0.691 in the validation cohort). The time-varying AUCs for both the ML model and the A-HIPI were consistently higher in both cohorts compared with the IPS models within the first 5 years after diagnosis.ConclusionThe new prognostic model for aHL on the basis of ML techniques demonstrated a substantial improvement compared with the IPS models, but yielded a limited improvement in predictive performance compared with the A-HIPI.
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| 10. |
- Ovlisen, Andreas K., et al.
(author)
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Parenthood Rates and Use of Assisted Reproductive Techniques in Younger Hodgkin Lymphoma Survivors : A Danish Population-Based Study
- 2021
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In: Journal of Clinical Oncology. - : American Society of Clinical Oncology (ASCO). - 0732-183X .- 1527-7755. ; 39:31, s. 3463-3472
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Journal article (peer-reviewed)abstract
- PURPOSE The majority of young adults with Hodgkin lymphoma (HL) are cured, but chemotherapy-induced infertility can have profound psychosocial consequences. Providing data on parenthood rates and use of assisted reproductive techniques (ARTs) after contemporary HL treatment is important for patient counseling and survivorship care.MATERIALS AND METHODS All Danish patients with HL diagnosed during 2000-2015 at the ages 18-40 years who achieved remission after first-line therapy were included and matched on age, sex, and parenthood status to five random persons from the general population. Parenthood rates were defined as the rate of first live birth per 1,000 person years, starting 9 months after HL diagnosis. Nationwide birth and patient registers were used to capture parenthood outcomes and ARTs use.RESULTS A total of 793 HL survivors and 3,965 comparators were included (median follow-up 8.7 years). Similar parenthood rates were observed for male and female HL survivors when compared with matched comparators (56.2 v 57.1; P = .871 for males and 63.8 v 61.2; P = .672 for females). For male HL survivors, BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) therapy was associated with lower parenthood rates as compared to the matched comparators (28.1 v 60.8; P = .020). Live birth after ARTs were more common for HL survivors than for comparators (males 21.6% v 6.3%; P < .001; females 13.6% v 5.5%; P = .001). There were no differences in gestational age, Apgar score, or newborn measurements between HL survivors and matched comparators.CONCLUSION The parenthood rates for HL survivors who have not experienced relapse were generally similar to the general population. However, ARTs were used more often before the first live birth in HL survivors, which is relevant information when discussing possible long-term side effects and fertility-preserving treatment options.
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| 11. |
- Pulczynski, Elisa Jacobsen, et al.
(author)
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Age-adjusted combined immunochemotherapy without radiotherapy in newly diagnosed PCNSL : A phase II trial of the Nordic Lymphoma Group
- 2011
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In: 53rd ASH Anual Meeting and Exposition. ; , s. 696-696
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Conference paper (peer-reviewed)abstract
- Patients and Methods: From May 2007 to October 2010, 66 newly diagnosed primary central nervous system lymphoma (PCNSL) patients (M/F ratio 1:1) were enrolled. Younger patients (≤65 yrs; N=39) received 6 three-weekly cycles of chemotherapy consisting of: high-dose (HD)-methotrexate (MTX) (cycles 1, 2, 4 and 5), HD-cytosine arabinoside (AraC) (cycles 3 and 6) in addition to Rituximab (cycle 1 only), ifosfamide (cycles 1 and 4), cyclophosphamide (cycles 2 and 5), vincristine (cycles 2 and 5), vindesine (cycles 3 and 6), and dexamethasone (all 6 cycles). Depocyte® was delivered intratechally during the HD-MTX cycles. Elderly patients (66-75 yrs; N=27) received an identical Rituximab-containing 1st cycle. Cyclophosphamide and ifosfamide were replaced by temozolamide (cycles 2 to 6), which was also given as maintenance in patients with chemosensitive disease, and vincristine was omitted. No radiotherapy was given. Response was determined after the 2nd, 4th and 6thchemotherapy cycle by cerebral MRI and assessed according to International Primary CNS Lymphoma Coordinating Group criteria. The primary endpoint was overall survival (OS), secondary endpoints were progression-free survival (PFS), overall response rate (ORR), systemic toxicity and neurotoxicity assessed as Mini Mental State Examination (MMSE) and Functional Independence Measure (FIM). Results: The median age was 64 yrs overall, 55 yrs (range 40-65) for younger and 70 yrs (range 66-75 years) for elderly patients. In 56 patients, the International Extranodal Lymphoma Study Group prognostic score was: 0-1 (N=5), 2-3 (N=36) and 4-5 (N=15). In the remaining 10 patients, lumbar puncture was not performed in five and spinal fluid protein concentration not reported in additional five cases. Response assessment after completion of induction treatment was performed in 43 out of 66 patients and showed complete remission (CR/CRu) in 30 patients, partial remission (PR) in 5 and progressive disease (PD) in 8. The ORR was 53 %. In 23 patients, response could not be evaluated due to early progression (n=8), toxic death (n=4), poor performance (n=3), neurotoxicity (n=5), or other causes (n=3). Of the 27 elderly patients, 15 continued to maintenance therapy. Of these, 14 have completed the maintenance schedule. Remission status at month 3 was CR in 13 and PD in 1 patient. With a median follow-up of 11.1 months (range 0.6-40.2) the 3-yr OS was 54.6% with no significant difference between younger and elderly patients (56.4% vs 51.9% respectively, p=0.32). The 3-yr PFS was 35.1% (32.9% in younger and 38.2 % in elderly patients; p=0.96). There were four septic deaths. Grade 3-4 hematological toxicity was seen in 79 % of the patients. Arachnoditis-like symptoms occurred in 13 patients. In all but two patients, the symptoms resolved within less than a week. MMSE and FIM were recorded both before and after therapy in 32 patients. Scores improved in 18 and 20 patients, respectively. Conclusion: In conclusion, the schedule applied in the present study led to a 3 yr PFS of 35%. Surprisingly, no significant outcome difference was found between the younger and the elderly patients. The majority of treatment failures were due to early progressive disease under induction therapy. Although the follow-up of our study is short, de-escalation of induction treatment intensity by introduction of a less toxic agent as temozolomide, and its subsequent use in a maintenance schedule may explain a possible survival benefit of this strategy in elderly patients. Disclosures: No relevant conflicts of interest to declare.
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| 12. |
- Stemann Larsen, Pernille, et al.
(author)
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Pregnancy and Birth Cohort Resources in Europe: a Large Opportunity for Aetiological Child Health Research
- 2013
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In: Paediatric and Perinatal Epidemiology. - : Wiley-Blackwell. - 0269-5022 .- 1365-3016. ; 27:4, s. 393-414
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Research review (peer-reviewed)abstract
- Background During the past 25 years, many pregnancy and birth cohorts have been established. Each cohort provides unique opportunities for examining associations of early-life exposures with child development and health. However, to fully exploit the large amount of available resources and to facilitate cross-cohort collaboration, it is necessary to have accessible information on each cohort and its individual characteristics. The aim of this work was to provide an overview of European pregnancy and birth cohorts registered in a freely accessible database located at http://www.birthcohorts.net. Methods European pregnancy and birth cohorts initiated in 1980 or later with at least 300 mother-child pairs enrolled during pregnancy or at birth, and with postnatal data, were eligible for inclusion. Eligible cohorts were invited to provide information on the data and biological samples collected, as well as the timing of data collection. Results In total, 70 cohorts were identified. Of these, 56 fulfilled the inclusion criteria encompassing a total of more than 500000 live-born European children. The cohorts represented 19 countries with the majority of cohorts located in Northern and Western Europe. Some cohorts were general with multiple aims, whilst others focused on specific health or exposure-related research questions. Conclusion This work demonstrates a great potential for cross-cohort collaboration addressing important aspects of child health. The web site, http://www.birthcohorts.net, proved to be a useful tool for accessing information on European pregnancy and birth cohorts and their characteristics.
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