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Purpose: Evidence on the effect of self-protection via social distancing and wearing face-masks on infections during chemotherapy is currently not available. We asked if the occurrence of acute infections during chemotherapy for advanced-stage Hodgkin lymphoma (HL) decreased when COVID-19 protection measures were in effect. Methods: We analyzed the occurrence of infections during all documented eBEACOPP cycles starting between 01 March and 30 June of 2017 to 2020 in patients treated within the GHSG HD21 study in Germany and compared the infection rates and characteristics by logistic regression models and means of descriptive statistics. Results: We analyzed 911 cycles of 313 adult patients treated with 4 to 6 cycles of eBEACOPP. We found a significant decrease in the occurrence of infections during chemotherapy for HL during COVID-19 lockdown from 131 (19.6%) of 670 cycles in 2017–2019 to 30 (12.6%) of 239 cycles during COVID-19 lockdown [OR 0.574 (95% CI 0.354–0.930), P = 0.024]. The strongest effect was evident for unspecified infections with 39 cycles (5.8%) during 2017–2019 in comparison to 5 cycles (2.1%) during COVID-19 lockdown. 20 (24.1%) of 83 patients had an infection during the COVID-19 lockdown versus 99 (43.2%) of 229 patients in the years 2017–2019 (P = 0.0023). Conclusion: The significant decrease of infections during chemotherapy for HL during COVID-19 lockdown reveals the protective measures' potential to shield patients from transmissible pathogens. We conclude that these measures could be recommended for HL patients at risk for infections during chemotherapy. [ABSTRACT FROM AUTHOR]

Purpose: To overcome the limitations of traditional 1-dimensional fitness tests in analyzing physiological properties of badminton players, a badminton-specific endurance test (BST) was created. This study aimed at analyzing the influence of various fitness dimensions on BST performance. Methods: 18 internationally competing male German badminton players (22.4 ± 3.2 y, 79.2 ± 7.7 kg, 1.84 ± 0.06 m, world-ranking position [WRP] 21–501) completed a straight-sprint test, a change-of-direction speed test, various jump tests (countermovement jump, drop jump, standing long jump), a multistage running test (MST), and the BST. During this on-court field test players have to respond to a computerized sign indicating direction and speed of badminton-specific movements by moving into the corresponding corners. Results: Significant correlations were found between performance in MST and BST (individual anaerobic threshold [IAT], r = .63, P = .005; maximum velocity [Vmax], r = .60, P = .009). A negative correlation (r = –.59, P = .014) was observed between IAT in BST and drop-jump contact time. No further associations between performance indices could be detected. Apart from a small portion explained by MST results (IAT, R2 = .40; Vmax, R2 = .36), the majority of BST performance cannot be explained by the determined physiological correlates. Moreover, it was impossible to predict the WRP of a player on the basis of BST results (r = –.15, P = .55). Conclusions: Neither discipline-specific performance nor basic physiological properties were appropriately reflected by a BST in elite badminton players. This does not substantiate its validity for regular use as a testing tool. However, it may be useful for monitoring on-court training sessions. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to assess the use and outcome of rehabilitation after total laryngectomy in Germany. Methods: We enrolled patients who were scheduled for total laryngectomy, approached them again after surgery, after 3 months and 1 year. Patients completed questionnaires and were interviewed. Results: Of 309 participants, 14% had not received any rehabilitation. Reasons for nonuse were primarily ongoing treatment and poor health. Users of rehabilitation had 4 times the odds of attaining any ability to speak compared to nonusers (odds ratio 3.8, P = .02). The main aim of rehabilitation from the perspective of the users was speech rehabilitation, mentioned by 71% before starting rehabilitation. This was also what most users (27%) found the most helpful part of rehabilitation. Conclusions: Patients are interested in attending rehabilitation. They especially want to improve their speech capacity, which indeed is better among users of rehabilitation than in those without. [ABSTRACT FROM AUTHOR]

The LIFE Child study is a large population-based longitudinal childhood cohort study conducted in the city of Leipzig, Germany. As a part of LIFE, a research project conducted at the Leipzig Research Center for Civilization Diseases, it aims to monitor healthy child development from birth to adulthood and to understand the development of lifestyle diseases such as obesity. The study consists of three interrelated cohorts; the birth cohort, the health cohort, and the obesity cohort. Depending on age and cohort, the comprehensive study program comprises different medical, psychological, and sociodemographic assessments as well as the collection of biological samples. Optimal data acquisition, process management, and data analysis are guaranteed by a professional team of physicians, certified study assistants, quality managers, scientists and statisticians. Due to the high popularity of the study, more than 3000 children have already participated until the end of 2015, and two-thirds of them participate continuously. The large quantity of acquired data allows LIFE Child to gain profound knowledge on the development of children growing up in the twenty-first century. This article reports the number of available and analyzable data and demonstrates the high relevance and potential of the study. [ABSTRACT FROM AUTHOR]

Background: The LIFE-Adult-Study is a population-based cohort study, which has recently completed the baseline examination of 10,000 randomly selected participants from Leipzig, a major city with 550,000 inhabitants in the east of Germany. It is the first study of this kind and size in an urban population in the eastern part of Germany. The study is conducted by the Leipzig Research Centre for Civilization Diseases (LIFE). Our objective is to investigate prevalences, early onset markers, genetic predispositions, and the role of lifestyle factors of major civilization diseases, with primary focus on metabolic and vascular diseases, heart function, cognitive impairment, brain function, depression, sleep disorders and vigilance dysregulation, retinal and optic nerve degeneration, and allergies. Methods/design: The study covers a main age range from 40-79 years with particular deep phenotyping in elderly participants above the age of 60. The baseline examination was conducted from August 2011 to November 2014. All participants underwent an extensive core assessment programme (5-6 h) including structured interviews, questionnaires, physical examinations, and biospecimen collection. Participants over 60 underwent two additional assessment programmes (3-4 h each) on two separate visits including deeper cognitive testing, brain magnetic resonance imaging, diagnostic interviews for depression, and electroencephalography. Discussion: The participation rate was 33 %. The assessment programme was accepted well and completely passed by almost all participants. Biomarker analyses have already been performed in all participants. Genotype, transcriptome and metabolome analyses have been conducted in subgroups. The first follow-up examination will commence in 2016. [ABSTRACT FROM AUTHOR]

Background: A high proportion of patients with relapsed classical Hodgkin's lymphoma achieve a response with the antibody-drug conjugate brentuximab vedotin, and the drug is well tolerated. We modified the escalated BEACOPP regimen (eBEACOPP; bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) and implemented brentuximab vedotin with the aim to reduce toxic effects while maintaining the protocol's efficacy.Methods: We did an open-label, multicentre, randomised phase 2 study at 20 study sites in Germany. Adult patients (aged 18-60 years) with newly diagnosed, advanced, classical Hodgkin's lymphoma were randomly assigned (1:1) to treatment with six cycles of either BrECAPP (brentuximab vedotin 1·8 mg/kg on day 1, etoposide 200 mg/m2 on days 2-4, doxorubicin 35 mg/m2 on day 2, cyclophosphamide 1250 mg/m2 on day 2, procarbazine 100 mg/m2 on days 2-8, and prednisone 40 mg/m2 on days 2-15) or BrECADD (brentuximab vedotin 1·8 mg/kg on day 1, etoposide 150 mg/m2 on days 2-4, doxorubicin 40 mg/m2 on day 2, cyclophosphamide 1250 mg/m2 on day 2, dacarbazine 250 mg/m2 on days 3-4, and dexamethasone 40 mg on days 2-5). Randomisation was done centrally by stratified minimisation, with study site and sex as stratification factors. The co-primary endpoints were complete response to chemotherapy and complete remission at the end of treatment, which were assessed by intention to treat. Patients who were found not to meet inclusion criteria after randomisation or without restaging data after two cycles of study treatment were excluded from the primary endpoint analysis. All patients who started study treatment were assessable for safety. This report presents the final analysis at a median follow-up of 17 months (IQR 13·2-21·5). The preplanned 2-year follow-up analysis is yet to be reported. This trial is registered with ClinicalTrials.gov, number NCT01569204.Findings: Between Oct 26, 2012, and May 15, 2014, 104 patients were enrolled to the study (52 were assigned to each study arm). Two patients dropped out before the start of study treatment because of acute infection (n=1) and withdrawal of consent (n=1) and one patient was excluded because of intermediate-stage disease (all were assigned BrECAPP). 42 (86%, 95% CI 73-94) of 49 patients assigned BrECAPP achieved a complete response after chemotherapy and 46 (94%, 95% CI 83-99) had complete remission as their final treatment outcome. In the BrECADD group, 46 (88%, 95% CI 77-96) of 52 patients achieved both a complete response after chemotherapy and complete remission as their final treatment outcome. 58 serious adverse events were reported, 32 events in 21 of 50 patients who received BrECAPP and 26 events in 18 of 52 patients who received BrECADD. The most common grade 3-4 toxic effects were haematological adverse events (91 [89%] of 102 patients). Grade 3-4 organ toxic effects were reported in seven (17%) of 42 patients assigned BrECAPP and two (4%) of 46 allocated BrECADD. 16 (32%) of 50 patients assigned BrECAPP and 18 (35%) of 52 allocated BrECADD had grade 1-2 peripheral neuropathy, and one (2%) patient assigned BrECAPP developed grade 3 peripheral neuropathy; all but one case (allocated BrECAPP) resolved. No deaths were reported during the follow-up period.Interpretation: Both eBEACOPP variants met the co-primary efficacy endpoints. Particularly, the BrECADD regimen was associated with a more favourable toxicity profile and was, therefore, selected to challenge standard eBEACOPP for the treatment of advanced classical Hodgkin's lymphoma in the phase 3 HD21 study by the German Hodgkin Study Group (NCT02661503), which aims to further reduce treatment-related morbidity.Funding: Takeda Pharmaceuticals. [ABSTRACT FROM AUTHOR]

Objective: People with hearing handicap have to use a whole range of strategies to cope with everyday challenges - they have to self-manage their hearing impairment. While the support of self-management is well established in foreign language audiological rehabilitation programs, there are no recommendations in Germany yet. Therefore, the aim of this systematic review is first to give an overview of existing self-management interventions for people with hearing handicap and then to suggest possible applications in the German care system., Methods: A systematic literature search was conducted on PubMed. The articles dealt with self-management interventions for people with hearing impairment. This eligibility criterion was applied to titles, abstracts, and full texts. If eligible, information on the publication, intervention, and evaluation were extracted and qualitatively summarized. The methodological quality of studies was investigated using the NIH assessment tool for interventional studies., Results: 23 papers could be included and show a high heterogeneity regarding methodological quality, applied intervention, and design of evaluation. The interventions pursuing various goals include a wide range of content (e. g., communication improvement or psychosocial aspects) and have been implemented on a group-based, individual-based, or self-administered level. Despite a few studies that failed to demonstrate intervention effects, most evaluations found positive ef-fects of the intervention on hearing impairment, psychological well-being, and communication., Discussion: The included studies present a high heterogeneity with regard to methodological quality, the intervention conducted, and the evaluation design. Therefore, a summary of the findings was only possible in a qualitative manner. Possibilities of adapting existing intervention programs as well as chances and limits of an implementation in the German health care system are to be discussed in the following., Conclusion: Overall, interventions including self-management support seem to be a profitable complement to sole technical device supply and should be further fostered in German-speaking countries as well., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

To evaluate patterns of rrHL after contemporary first-line treatment we studied 409 patients with first rrHL (HD13: n = 87, HD14: n = 118, HD15: n = 188, HDR3i: n = 51) at a median age of 37.4 years (18.4-76.8) from the GHSG database. Time to first relapse was ≤12 months in 49% and stage III/IV rrHL present in 52% of patients. In total, 291 patients received high-dose chemotherapy and autologous stem-cell transplantation (ASCT) and intended ASCT failed in 38 patients. ASCT was primarily not intended in 80 patients largely due to low risk disease or age/comorbidities. Overall, 10-year progression-free (PFS) and overall survival (OS) rates after first relapse were 48.2% (95% CI 41.9-54.2%) and 59.4% (95% CI 53.0-65.2%), respectively, with significant differences between subgroups. Inferior survival was observed with no ASCT due to advanced age/comorbidities (five-year PFS 36.2%, 95% CI 17.7-55.0%) or failure of salvage therapy (five-year PFS 36.3%, 95% CI 19.7-53.2%). Similarly, presence of primary refractory disease or stage IV at rrHL conferred inferior survival. In patients with low-risk disease, however, survival appeared favorable even without ASCT (10 y PFS 72.6%, 95% CI 53.7-84.8%). We herein confirm the curative potential of current rrHL treatments providing a robust benchmark to evaluate novel therapeutic strategies in rrHL. Approximately 50% of rrHL patients experienced a consecutive relapse., (© 2021. The Author(s).)

Reinduction chemotherapy followed by high-dose chemotherapy and autologous stem cell transplant (HDCT + ASCT) is second-line standard of care for transplant-eligible patients with relapsed/refractory classical Hodgkin lymphoma (r/r cHL) but has a high failure rate. Because response to reinduction is predictive of the outcome after HDCT + ASCT, we aimed to improve the standard dexamethasone, high-dose cytarabine and cisplatinum (DHAP) reinduction regimen by addition of the oral mammalian target of rapamycin inhibitor everolimus (everDHAP). Transplant-eligible patients aged 18-60 years with histologically confirmed r/r cHL were included in this experimental phase I/II trial. Everolimus (10 mg/day, determined in phase-I-part) was administered on day 0-13 of each DHAP cycle. From July 2014 to March 2018, 50 patients were recruited to the phase II everDHAP group; two were not evaluable, three discontinued due to toxicity. Randomization to a placebo group stopped in October 2015 due to poor recruitment after nine patients. The primary end-point of computed tomography (CT)-based complete remission (CR) after two cycles of everDHAP was expected to be ≥40%. With a CT-based CR rate of 27% (n = 12/45) after two cycles of everDHAP the trial did not meet the primary end-point. Adding everolimus to DHAP is thus feasible; however, the everDHAP regimen failed to show an improved efficacy., (© 2021 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

High programmed cell death 1 ligand 1 (PD-L1) protein expression and copy number alterations (CNAs) of the corresponding genomic locus 9p24.1 in Hodgkin- and Reed-Sternberg cells (HRSC) have been shown to be associated with favourable response to anti-PD-1 checkpoint inhibition in relapsed/refractory (r/r) classical Hodgkin lymphoma (cHL). In the present study, we investigated baseline 9p24.1 status as well as PD-L1 and major histocompatibility complex (MHC) class I and II protein expression in 82 biopsies from patients with early stage unfavourable cHL treated with anti-PD-1-based first-line treatment in the German Hodgkin Study Group (GHSG) NIVAHL trial (ClinicalTrials.gov Identifier: NCT03004833). All evaluated specimens showed 9p24.1 CNA in HRSC to some extent, but with high intratumoral heterogeneity and an overall smaller range of alterations than reported in advanced-stage or r/r cHL. All but two cases (97%) showed PD-L1 expression by the tumour cells in variable amounts. While MHC-I was rarely expressed in >50% of HRSC, MHC-II expression in >50% of HRSC was found more frequently. No obvious impact of 9p24.1 CNA or PD-L1 and MHC-I/II expression on early response to the highly effective anti-PD-1-based NIVAHL first-line treatment was observed. Further studies evaluating an expanded panel of potential biomarkers are needed to optimally stratify anti-PD-1 first-line cHL treatment., (© 2021 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Data on non-Hodgkin lymphoma (NHL) after classical Hodgkin lymphoma (cHL) are scarce. We therefore performed a retrospective analysis comprising 11·841 cHL patients who had first-line treatment within the randomized German Hodgkin Study Group (GHSG) HD7-HD15 studies. After a median follow-up of 106 months, 175 patients (1·5%) had developed NHL. The median time to NHL was 44 months, the median age at NHL diagnosis was 54 years. The five-year event-free survival and overall survival estimates from the diagnosis of NHL were 36·9% and 44·2%, respectively. Thus, NHL after cHL is a rare event primarily affecting older individuals and often resulting in the patient´s death., (© 2021 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Background: To improve the long-term tumour control in early, unfavourable Hodgkin Lymphoma, the German Hodgkin Study Group (GHSG) HD14 trial compared four cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) with an intensified chemotherapy regimen consisting of two cycles of escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (escalated BEACOPP) plus two cycles of ABVD. The final analysis of the trial showed a significant advantage in terms of freedom from treatment failure (difference 7·2% [95% CI 3·8-10·5] at 5 years) for patients who received two cycles of escalated BEACOPP and two cycles of ABVD. However, there was no difference in overall survival between the two groups. To evaluate long-term efficacy and toxicity of this strategy, we did a follow-up analysis., Methods: Patients aged 18-60 years with performance status of 2 or less and primary diagnosis of early, unfavourable Hodgkin lymphoma (all histologies) were included in an international, randomised, open-label, phase 3 trial. Patients were randomly assigned to receive four cycles of ABVD (ABVD group) or two cycles of escalated BEACOPP and two cycles of ABVD (2 + 2 group), both groups also received 30 Gy involved field radiotherapy. The ABVD dosing regimen was doxorubicin 25 mg/m 2 (days 1 and 15), bleomycin 10 mg/m 2 (days 1 and 15), vinblastine 6 mg/m 2 (days 1 and 15), and dacarbazine 375 mg/m 2 (days 1 and 15), repeated on day 29. The escalated BEACOPP dosing regimen was cyclophosphamide 1250 mg/m 2 (day 1), doxorubicin 35 mg/m 2 (day 1), etoposide 200 mg/m 2 (days 1-3), procarbazine 100 mg/m 2 (days 1-7), prednisone 40 mg/m 2 (days 1-14), vincristine 1·4 mg/m 2 (day 8; maximum 2 mg), and bleomycin 10 mg/m 2 (day 8), repeated on day 22. After closure of the ABVD group according to prespecified rules, patients were assigned to receive two cycles of escalated BEACOPP and two cycles of ABVD (non-randomised 2 + 2 group), which continued until the end of the predefined 5-year recruitment period. In this prespecified long-term follow-up analysis, we aimed to evaluate the secondary endpoints progression-free survival, overall survival, and long-term toxicity. To this end, we did a descriptive intention-to-treat analysis of all qualified HD14 patients and on the predefined subsets of randomised qualified HD14 patients and patients in the non-randomised 2 + 2 group. The trial was registered on the International Standard Randomised Controlled Trial database, 04761296., Findings: Between Jan 28, 2003, and Dec 29, 2009, 1686 patients were randomly assigned to the ABVD group (847 [50·2%] patients) and the 2 + 2 group (839 [49·8%] patients). 370 additional patients were recruited to the non-randomised 2 + 2 group. 1550 (92%) randomly assigned patients (median observation time 112 months [IQR 80-132]) and 339 (92%) patients in the non-randomised 2 + 2 group (median observation time 74 months [58-100]) were included in the qualified analysis set. 10-year overall survival in the randomly assigned patients was 94·1% (95% CI 92·0-95·7) for the ABVD group and 94·1% (91·8-95·7) for the 2 + 2 group (HR 1·0 [95% CI 0·6-1·5]; p=0·88). 8-year overall survival in the non-randomised 2 + 2 group was 95·1% (95% CI 91·6-97·2). 10-year progression-free survival in the randomly assigned patients was 85·6% (95% CI 82·6-88·1) for the ABVD group and 91·2% (88·4-93·3) for the 2 + 2 group (HR 0·5% [95% CI 0·4-0·7]; p=0·0001), accounting for a significant difference of 5·6% (95% CI 1·9-9·2) favouring the 2 + 2 group (p=0·0001). In the non-randomised 2 + 2 group, 8-year progression-free survival was 94·5% (95% CI 91·1-96·6). Standardised incidence ratios of second primary malignancies were similar between the ABVD group (2·3 [95% CI 1·6-3·1]) and the 2 + 2 group (2·5 [1·8-3·4]; Gray's p=0·80). Standardised incidence ratio of second primary malignancies was 3·1 (95% CI 1·7-5·0) in the non-randomised 2 + 2 group., Interpretation: This long-term analysis confirms superior tumour control in the 2 + 2 group compared with the ABVD group without translating into an overall survival difference. At longer follow-up, there is no difference regarding second primary malignancies between groups. In conclusion, the 2 + 2 regimen spares a significant number of patients from the burden of relapse and additional treatment without increased long-term toxicity., Funding: Deutsche Krebshilfe eV and Swiss Federal Government., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: Communication skills are an essential instrument for building a sustainable patient-doctor-relationship for future doctors. They are learnable and teachable. The learning should be facilitated with the help of a longitudinal curriculum, which is planned at Leipzig University. Project: At the Medical Faculty of Leipzig University, the Longitudinal Communication Curriculum is established since 2016/17. Up to now, the curriculum consists of four parts in which students repeatedly practise their communication skills in curricular and extracurricular courses. Several formats help to teach an integrated learning of communication and physical examination skills. Assessment of communication skills is also performed. Curricular implementation is accompanied by concomitant evaluation. Results: Three parts of the curriculum already have taken place. Students report an increase in communication skills. Students rate the units as instructive and helpful. The assessment of communication skills occurs in two clinical practical examinations (OSCEs). Together with summative assessment a formative feedback was implemented. Students judge this practice as highly positive. Discussion: The curriculum is part of undergraduate medical education in Leipzig. It would be beneficial to add another simulated patient encounter, as well as interprofessional units. Student questionnaires will be evaluated and results will help to develop the curriculum. Conclusion: Consolidation of the curriculum accompanied by evaluation and adaption of content can help to assure the quality of the curriculum. Additional professions and study units shall be integrated in the Longitudinal Communication Curriculum in the future., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2021 Zimmermann et al.)

Background: In Germany, there are specialized vocational training units (BBW) for adolescents and young adults with special needs. The BBW Leipzig for people with disorders in hearing, language and communication registers a rising number of adolescents with auditory processing disorder (APD). However, test material to diagnose APD at this age is sparse. This study investigates auditory processing in adolescents with normal hearing but communication impairment with the available test material., Materials and Methods: 35 normal hearing adolescents (26 male, 9 female, mean age: 18.1 years) were included. All were trained at BBW Leipzig. Dichotic listening, understanding of speech in noise, accelerated speech, differentiation and analysis of phonemes were examined. In addition, non-verbal general intelligence, concentration, figural retentivity, and linguistic abilities were assessed., Results: 25 participants showed conspicious results concerning APD; 5 had never been diagnosed with APD so far. In 9/25 adolescents, there was no hint of top-down disorders. These participants had problems in accessing auditory information and holding and manipulating information in working memory, although both linguistic and intellectual abilities were normal or even above average., Conclusions: The study has shown that adolescents can be conspicuous according to the APD criteria of the DGPP and that an APD diagnosis from childhood is not necessarily already present. It also became clear that multi-professional diagnostics remains important beyond childhood. Standardized tests with corresponding age norms are needed., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Purpose: Many important details of health-related quality of life (HRQoL) after diagnosis and treatment of Hodgkin lymphoma (HL) are still unknown because large longitudinal studies of HRQoL are rare. Therefore, we analyzed a systematically assessed, comprehensive range of HRQoL domains in patients with HL of all stages from diagnosis up to 5 years of survivorship., Patients and Methods: We included patients with HL age 18-60 years at diagnosis from the German Hodgkin Study Group trials HD13, HD14, and HD15. We analyzed HRQoL using all functional and symptom scales of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 including deviations from reference values. We estimated the effect of different disease, patient, and treatment characteristics using multiple regression and repeated measures analysis and computed correlations of HRQoL scores., Results: We analyzed 4,215 patients with any HRQoL assessment within 5 years after treatment. Higher tumor burden at diagnosis was associated with impaired baseline scores in many HRQoL domains. During survivorship, cognitive, emotional, role, and social functioning and fatigue, dyspnea, sleep, and financial problems were severely and persistently affected. From year 2 on, mean deviations from reference values ranged between 12 and 29 points, with 10 points being a commonly used margin of clinical relevance. In all 3 trials, HRQoL domains 2 and 5 years after therapy were significantly influenced by baseline scores and age but not by randomized treatments. Fatigue was most closely correlated with other symptoms and scales., Conclusion: Our results show a high and persistent amount of different HRQoL deficits in survivors of HL that are largely independent of the applied chemotherapies. Our analysis underscores the high, unmet medical need of these rather young survivors of HL regarding the psychosocial adverse effects of the cancer experience.

Importance: In early-stage unfavorable classic Hodgkin lymphoma (cHL), conventional therapy induces high cure rates but also relevant acute and long-term toxic effects. Nivolumab is well tolerated and highly effective in relapsed/refractory cHL but has not been adequately studied in first-line treatment of early-stage cHL. The NIVAHL trial evaluated nivolumab in this setting with the aim to develop a highly effective yet tolerable systemic therapy to ultimately mitigate morbidity in patients who survive cHL., Objective: To evaluate efficacy of 2 experimental nivolumab-based first-line treatment strategies in patients with early-stage unfavorable cHL., Design, Setting, and Participants: This was an open-label, multicenter, phase 2 randomized clinical trial, open between April 2017 and October 2018. The trial took place at 35 trial centers across Germany, ranging from academic centers to private offices. Eligibility was defined by age 18 to 60 years, cHL confirmed by expert pathology review, early-stage unfavorable disease by German Hodgkin Study Group criteria (stage I to II with risk factor[s]), and absence of serious concomitant disease or organ dysfunction. Among 110 enrolled patients, 109 were eligible., Interventions: Systemic therapy, per random assignment (1:1) to either concomitant treatment with 4 cycles of nivolumab and doxorubicin, vinblastine, and dacarbazine (N-AVD) or sequential treatment with 4 doses of nivolumab, 2 cycles of N-AVD, and 2 cycles of AVD at standard doses, followed by 30-Gy involved-site radiotherapy., Main Outcomes and Measures: Complete remission (CR) rate after study treatment, aiming at excluding a CR rate of 80% or lower via a 2-sided 95% CI for each treatment group., Results: Of 109 patients included in this study, 65 (59.6%) were women, and the median (range) age was 27 (18-60) years. At interim staging after 2 cycles of N-AVD or 4 doses of nivolumab monotherapy, 54 of 54 (100%) and 49 of 51 (96%) response-eligible patients, respectively, achieved an objective response, with CR in 47 (87%) and 26 (51%) patients, respectively. Among 101 patients eligible for primary end point analysis, 46 of 51 (90%; 95% CI, 79%-97%) patients receiving concomitant therapy and 47 of 50 (94%; 95% CI, 84%-99%) patients receiving sequential therapy achieved CR after study treatment. With a median follow-up of 13 months, 12-month progression-free survival was 100% for patients receiving concomitant treatment and 98% (95% CI, 95%-100%) for patients receiving sequential therapy., Conclusions and Relevance: Both strategies combining nivolumab and AVD are feasible and resulted in high remission rates. Despite narrowly missing the efficacy benchmark in the concomitant group, the excellent 12-month progression-free survival and the unexpectedly high CR rate after 4 doses of nivolumab monotherapy warrant further evaluation of this approach in the first-line treatment of patients with early-stage cHL., Trial Registration: ClinicalTrials.gov Identifier: NCT03004833.

The optimal treatment of patients with relapsed or refractory nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is ill defined. To shed more light on treatment options and outcome, we performed an analysis using the database of the German Hodgkin Study Group (GHSG). Ninety-nine patients who had received first-line treatment within 12 prospective GHSG studies conducted between 1993 and 2009, and subsequently developed disease recurrence (n = 91) or had primary disease progression (n = 8), were included. At initial NLPHL diagnosis, the median age was 40 years and 76% of patients were male. First-line treatment consisted of radiotherapy (RT) alone (20%), chemotherapy with or without RT (74%), and the anti-CD20 antibody (Ab) rituximab (6%), respectively. The median follow-up from initial diagnosis was 11.2 years. The median time to disease recurrence was 3.7 years. The applied salvage approaches included single-agent anti-CD20 Ab treatment or RT alone (37%), conventional chemotherapy (CT) with or without anti-CD20 Ab treatment with or without RT (27%) and high-dose chemotherapy (HDCT) followed by autologous stem cell transplantation (ASCT) (31%). No salvage treatment was given in 4% of patients. The 5-year progression-free survival and overall survival estimates after NLPHL recurrence were 75.6% and 89.5% (74.1% and 97.2% after single-agent anti-CD20 Ab treatment or RT alone; 68.0% and 77.8% after CT with or without anti-CD20 Ab treatment with or without RT; 84.6% and 89.8% after HDCT and ASCT). Hence, patients with relapsed or refractory NLPHL had a good overall prognosis. Factors such as time to disease recurrence and previous treatment may guide the choice of the optimal salvage approach for the individual patient., (© 2018 by The American Society of Hematology.)

Purpose: The role of bleomycin and vincristine in the treatment of patients with advanced Hodgkin lymphoma (HL) is unclear, and the impact of dose reductions of these drugs on outcome and tolerability has not been systematically assessed. Because both drugs can cause significant toxicity and are frequently discontinued, we performed an analysis of patients with HL treated with BEACOPP (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, and prednisone) in the German Hodgkin Study Group HD12 and HD15 trials., Patients and Methods: Characteristics and outcome of patients were analyzed with respect to discontinuation of bleomycin and/or vincristine., Results: With 3,309 patients with HL analyzed, bleomycin was discontinued in 17.6% and vincristine in 32.6%. A total of 157 patients (4.7%) received ≤ four cycles of bleomycin, and 218 (6.6%) received ≤ three cycles of vincristine; these were compared with patients receiving > four cycles of bleomycin or > three cycles of vincristine, respectively. After a median follow-up of 59 and 67 months for progression-free survival (PFS) and overall survival (OS), respectively, there was no significant difference in PFS or OS in patients receiving ≤ or > four cycles of bleomycin (5-year PFS difference, 1.7%; 95% CI, -4.2% to 7.6%; 5-year OS difference, 1.5%; 95% CI, -2.6% to 5.5%). Similarly, there was no significant difference in patients receiving ≤ or > three cycles of vincristine (5-year PFS difference, -1.3%; 95% CI, -5.6% to 3.1%; 5-year OS difference, -0.1%; 95% CI, -3.1% to 2.9%)., Conclusion: Bleomycin and vincristine discontinuation because of drug-specific adverse effects does not affect the efficacy of treatment in this setting., (© 2015 by American Society of Clinical Oncology.)

Therapy-related acute myeloid leukemia and myelodysplastic syndromes (t-AML/MDS) represent severe late effects in patients treated for Hodgkin lymphoma (HL). Because more recent data are scarce, we retrospectively analyzed incidence, outcome, and risk factors for the development of t-AML/MDS after HL. A total of 11,952 patients treated for newly diagnosed HL within German Hodgkin Study Group trials between 1993 and 2009 were considered. At a median follow-up of 72 months, t-AML/MDS was diagnosed in 106/11,952 patients (0.9%). Median time from HL treatment to t-AML/MDS was 31 months. The median age of patients with t-AML/MDS was higher than in the whole patient group (43 vs 34 years, P < .0001). Patients who received 4 or more cycles of BEACOPP(escalated) had an increased risk to develop t-AML/MDS when compared with patients treated with less than 4 cycles of BEACOPP(escalated) or no BEACOPP chemotherapy (1.7% vs 0.7% vs 0.3%, P < .0001). The median overall survival (OS) for all t-AML/MDS patients was 7.2 months. However, t-AML/MDS patients proceeding to allogeneic stem cell transplantation had a significantly better outcome with a median OS not reached after a median follow-up of 41 months (P < .001).

Purpose: Progression or relapse of Hodgkin lymphoma (HL) is common among older patients. However, prognosis and effects of second-line treatment are thus far unknown., Patients and Methods: We investigated second-line treatment and survival in older patients with progressive or relapsed HL. Patients treated within German Hodgkin Study Group first-line studies between 1993 and 2007 were screened for refractory disease or relapse (RR-HL). Patients with RR-HL age ≥ 60 years at first-line treatment were included in this analysis., Results: We identified 105 patients (median age, 66 years); 28%, 31%, and 41% had progressive disease, early relapse, or late relapse, respectively. Second-line treatment strategies included intensified salvage regimens (22%), conventional polychemotherapy and/or salvage-radiotherapy with curative intent (42%), and palliative approaches (31%). Median overall survival (OS) for the entire cohort was 12 months; OS at 3 years was 31% (95% CI, 22% to 40%). A prognostic score with risk factors (RFs) of early relapse, clinical stage III/IV, and anemia identified patients with favorable and unfavorable prognosis (≤ one RF: 3-year OS, 59%; 95% CI, 44% to 74%; ≥ two RFs: 3-year OS, 9%; 95% CI, 1% to 18%). In low-risk patients, the impact of therapy on survival was significant in favor of the conventional polychemotherapy/salvage radiotherapy approach. In high-risk patients, OS was low overall and did not differ significantly among treatment strategies., Conclusion: OS in older patients with RR-HL can be predicted using a simple prognostic score. Poor outcome in high-risk patients cannot be overcome by any of the applied treatment strategies. Our results might help to guide treatment decisions and evaluate new compounds in these patients.

Purpose: To optimize fertility advice in patients with Hodgkin lymphoma (HL) before therapy and during survivorship, information on the impact of chemotherapy is needed. Therefore, we analyzed gonadal functions in survivors of HL., Patients and Methods: Women younger than age 40 and men younger than 50 years at diagnosis in ongoing remission at least 1 year after therapy within the German Hodgkin Study Group HD13 to HD15 trials for early- and advanced-stage HL were included. Hormone parameters, menstrual cycle, symptoms of hypogonadism, and offspring were evaluated., Results: A total of 1,323 (55%) of 2,412 contacted female and male survivors were evaluable for the current analysis (mean follow-up, 46 and 48 months, respectively). Follicle-stimulating hormone, anti-Müllerian hormone, and inhibin B levels correlated significantly with therapy intensity (P < .001). Low birth rates were observed in survivors after advanced-stage treatment within the observation time (women, 6.5%; men, 3.3%). Regular menstrual cycle was reported by more than 90% of female survivors of early-stage HL (recovery time mostly ≤ 12 months). After six to eight cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone, menstrual activity was strongly related to age (< v ≥ 30 years: 82% v 45%, respectively; P < .001; prolonged recovery time). Thirty-four percent of women age ≥ 30 years suffered severe menopausal symptoms (three- to four-fold more frequently than expected). In contrast, male survivors had mean levels of testosterone within the normal range and reported no increased symptoms of hypogonadism., Conclusion: The present analysis in a large group of survivors of HL provides well-grounded information on gonadal toxicity of currently used treatment regimens and allows risk-adapted fertility preservation and comprehensive support during therapy and follow-up.

Background: The purpose of this study was to evaluate the effect of legal regulations for clinical trials on study centers participating in investigator-initiated trials (IITs) in the field of hematology/oncology., Method: Questionnaires were sent out to the heads of hematology-oncology study centers., Results: Medical units participating in IITs have a good infrastructure and extensive experience in clinical trials. Depending on indication, a high proportion of patients have been treated in studies with the purpose to improve outcome. However, 35% of the responders will reduce their participation in IITs in the future due to a lack of financial support for staff involved in the extensive organizational tasks., Conclusions: The widely recognized research field in therapy optimization trials in hematology and oncology in Germany is at risk. This will have negative effects on the patients as highly sophisticated protocols will no longer be initiated in several study centers, resulting in the loss of valuable data for the improvement of patient therapy and outcome. To stop this development, legislators as well as regulatory authorities and health insurances need to make the necessary changes in the legal framework., (Copyright © 2013 S. Karger AG, Basel.)

Purpose: To investigate the clinical characteristics and treatment outcome of patients with lymphocyte-depleted classical Hodgkin's lymphoma (LDCHL) compared with other histologic subtypes of Hodgkin's lymphoma (HL)., Patients and Methods: From a total of 12,155 evaluable patients with biopsy-proven HL treated within the German Hodgkin Study Group trials HD4 to HD15, 10,019 patients underwent central expert pathology review. Eighty-four patients with LDCHL (< 1%) were identified and confirmed. The median follow-up time was 67 months., Results: Patients with LDCHL, compared with patients with other histologic subtypes, presented more often with advanced disease (74% v 42%, respectively; P < .001) and "B" symptoms (76% v 41%, respectively; P < .001). Other risk factors were also more frequent in patients with LDCHL. Complete remission or unconfirmed complete remission was achieved in 82% of patients with LDCHL compared with 93% of patients with other HL subtypes (P < .001), and more patients with LDCHL had progressive disease. At 5 years, progression-free survival (PFS) and overall survival (OS) were significantly lower in patients with LDCHL compared with patients with other HL subtypes (PFS, 71% v 85%, respectively; P < .001; OS, 83% v 92%, respectively; P = .0018). However, when analyzing the subgroup of patients who underwent treatment with intensified or dose-dense bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone, patients with LDCHL (n = 39) had similar outcomes when compared with patients with other subtypes of HL (n = 3,564; P = .61)., Conclusion: LDCHL has a different pattern from other HL subtypes with more clinical risk factors at initial diagnosis and significantly poorer prognosis. Patients with LDCHL should be treated with modern dose-intense treatment strategies.

Purpose: To determine whether epoetin alfa reduces anemia-related fatigue, improves other aspects of health-related patient-recorded outcomes (PROs), reduces the number of RBC transfusions, and has an impact on freedom from treatment failure (FFTF) and overall survival (OS) in patients with advanced-stage Hodgkin's lymphoma (HL)., Patients and Methods: The prospectively randomized HD15EPO study performed by the German Hodgkin Study Group investigated epoetin alfa administered at doses of 40,000 U weekly during and after chemotherapy (six to eight cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone [BEACOPP]) in a double-blind, placebo-controlled setting. The study accrued 1,379 patients, of whom 1,328 were assessable for safety, 1,303 were assessable for clinical outcome, and 930 were assessable for PROs., Results: PROs were not different in patients receiving placebo or epoetin alfa, both after the end of chemotherapy and 6 months thereafter. There was no difference between patients treated with epoetin alfa or placebo with respect to FFTF and OS. There were also no differences in the numbers of deaths, progressions, relapses, and thromboembolic events. The median number of RBC transfusions was reduced from four per patient in the placebo group to two per patient in the epoetin alfa group (P < .001), with 27.4% of patients needing no RBC transfusion in the placebo group compared with 36.7% of patients in the epoetin alfa group (P < .001)., Conclusion: Epoetin alfa administered at 40,000 U weekly parallel to BEACOPP chemotherapy was safe in patients with advanced-stage HL and reduced the number of RBC transfusions but had no impact on fatigue and other PRO domains.

The international transfer of human biomaterial and data has become a prerequisite for collaborative biomedical research to be successful. However, although a national legal framework for 'biobanking' has already been formulated in many countries, little is known about how an international exchange of data and samples might affect the legal position of national biobanks and their donors. The German Telematics Platform and the Competence Network 'Congenital Heart Defects' jointly instigated a project (BMB-EUCoop) to (i) identify and assess the legal risks ensuing for biobanks and their donors in the context of Europe-wide research collaborations, (ii) devise practical recommendations to minimize or avoid these risks, and (iii) provide generic informational text, contracts and agreements to facilitate their practical implementation. Four different countries were included in the study; namely, the UK, Netherlands, Austria and Switzerland. The results of the study indicate that the degree of similarity between legal systems in different countries varies according to the respective field of jurisdiction. Although personality and property rights have long been enshrined in virtually identical pieces of law, the applicable medical professional regulations were found to be somewhat heterogeneous. Furthermore, clear-cut differences were often found to be lacking between regulations that reflect either 'soft law' or the nationally binding 'hard law' that has emerged from it. In view of the potential ambiguities, the experts uniformly concluded that the rights and interests of national (in this case, German) biobanks and their donors would be best protected by explicitly addressing any uncertainties in formal contractual agreements.

PURPOSE The standard of care for adolescent patients with Hodgkin's lymphoma (HL) is undefined, particularly the choice between pediatric and adult protocols. Thus, we compared risk factors and outcome of adolescents and young adults treated within study protocols of the German Hodgkin Study Group (GHSG). PATIENTS AND METHODS Three thousand seven hundred eighty-five patients treated within the GHSG studies HD4 to HD9 were analyzed; 557 patients were adolescents age 15 to 20 years, and 3,228 patients were young adults age 21 to 45 years. Results Large mediastinal mass and involvement of three or more lymph node areas were more frequent in adolescents (P < .001). The incidence of other risk factors did not differ significantly between age groups. With a median observation time of 81 months for freedom from treatment failure (FFTF) and 85 months for overall survival (OS), log-rank test showed no significant differences between age groups regarding FFTF (P = .305) and a superior OS (P = .008) for adolescents. Six-year estimates for FFTF and OS were 80% and 94%, respectively, for adolescents and 80% and 91%, respectively, for young adults. After adjustment for other predictive factors, Cox regression analysis revealed age as a significant predictor for OS (P = .004), with a higher mortality risk for young adults. Secondary malignancies were more common in young adults (P = .037). CONCLUSION Outcome of adolescent and young adult patients treated within GHSG study protocols is comparable. These data suggest that adult treatment protocols exhibit a safe and effective treatment option for adolescent patients with HL. However, longer follow-up, including assessment of late toxicity, is necessary for final conclusions.

Objectives: The beta3-adrenergic receptor (ADRB3) is a transmembrane receptor highly expressed in adipose tissue and thought to be involved in the regulation of lipolysis. ADRB3 is also highly expressed in gallbladder tissue where it may be involved in gallbladder contraction. Because polymorphisms of ADRB3 are present in populations with a high prevalence of gallstones (e.g., Pima-Indians, obese subjects), we hypothesized that known polymorphisms for ADRB3 (Trp64Arg) may represent an independent risk factor for gallstone disease., Methods: The EMIL cross-sectional study investigated the health behavior and prevalence of chronic diseases in a small Southwestern German town of 12,475 inhabitants. From 3,893 randomly selected citizens 2,147 subjects were enrolled and screened for gallstones employing ultrasonography. Blood samples were drawn for biochemical analysis and isolation of genomic DNA. ADBR3 genotypes were determined by TaqMan SNP Assay., Results: We identified 171 (8%) gallstone carriers of whom 143 participated (46 male, 97 female), with a mean age of 51.4, and mean BMI of 29.3 kg/m2. For these subjects an age, gender and BMI matched partner without gallstones was recruited from the study population. Genotyping for ADRB3 revealed an Arg64 allele frequency of 5.9 versus 0.7% (HR = 11.9, P < 0.05) compared with controls., Conclusions: Our results indicate that the ADRB3 Trp64Arg polymorphism is associated with gallstone disease thereby representing a genetic marker that identifies subjects at higher risk for gallstone formation.