V posledných rokoch sa hodnotenie jazykových schopností osôb s kognitívnym deficitom zameriava na hodnotenie diskurzu. Konkrétne analýza informatívnosti sa ukazuje ako účinný diagnostický nástroj. Ide o hodnotenie, ktoré kombinuje štrukturalistický a funkcionalistický prístup k analýze diskurzu. Cieľom výskumu je zhodnotiť informatívnosť diskurzu osôb s demenciou pri Alzheimerovej chorobe (AD) a miernou kognitívnou poruchou (MCI). Výskumnú vzorku tvorí 25 osôb s AD, 25 osôb s MCI a 25 zdravých kontrol. Vzorky diskurzu sú elicitované pomocou opisu obrázkov. Na hodnotenie informatívnosti sa používa metóda analýzy hlavných konceptov. Výsledky výskumu nachádzajú signifikantné rozdiely vo výkonoch troch skupín výskumnej vzorky, pričom najviac konceptov vyjadrujú osoby z kontrolnej vzorky, nasleduje skupina MCI a najmenej konceptov vyjadruje skupina AD. Podľa výsledkov post-hoc testu sú signifikantné rozdiely v informatívnosti medzi AD a zdravými kontrolami, medzi MCI a zdravými kontrolami, ako aj medzi AD a MCI. Na základe výsledkov štúdie sa analýza hlavných konceptov, a teda hodnotenie informatívnosti ukazuje ako vhodná metóda na zachytenie jazykových ťažkostí pri AD a MCI. Cieľom ďalšieho výskumu by malo byť podrobné spracovanie metódy hodnotenia hlavných konceptov a jej spracovanie aj pre ďalšie elicitačné materiály bežne používané v slovenskej praxi.

In recent years, the assessment of the language abilities of persons with cognitive deficits has focused on discourse assessment. Specifically, the assessment of informativeness proves to be an effective diagnostic tool. This is an evaluation that combines a structuralist and functionalist approach to discourse analysis. The aim of this study is to evaluate discourse informativeness of persons with Alzheimer's dementia (AD) and mild cognitive impairment (MCI). The research sample consists of 25 persons with AD, 25 persons with MCI and 25 healthy controls. Discourse samples are elicited using picture description. Main concept analysis is used to evaluate informativeness. The results show significant differences in the performance of the three groups of the research sample, with the most concepts being expressed by people from the control sample, followed by the MCI group, and the least concepts being expressed by the AD group. According to the results of the post-hoc test, there are significant differences in informativeness between AD and healthy controls, between MCI and healthy controls, and also between AD and MCI. Based on the results of the study, main concept analysis and thus the evaluation of informativeness appears to be a suitable method for capturing language difficulties in AD and MCI. The goal of further research should be a detailed elaboration of main concept analysis and its application to other elicitation materials commonly used in Slovak practice.

• MeSH
• Alzheimerova nemoc * diagnóza   psychologie   MeSH
• duševně nemocní psychologie   MeSH
• jazyk (prostředek komunikace) MeSH
• kognitivní dysfunkce diagnóza   psychologie   MeSH
• lidé MeSH
• myšlení MeSH
• neuropsychologické testy MeSH
• stupeň závažnosti nemoci MeSH
• Check Tag
• lidé MeSH

Úvod: Zajakavosť predstavuje komplexné narušenie komunikačnej schopnosti, zvyčajne sa objavuje už v predškolskom veku. Napriek tomu, že u niektorých detí môže dôjsť k spontánnej náprave, považujeme za dôležité venovať sa terapii zajakavosti už v predškolskom veku, nakoľko u mnohých detí môže bez terapie pretrvávať problém do neskoršieho veku až dospelosti. Cieľ: V našom výskume sme sa rozhodli zmerať a porovnať prejavy zajakavosti pred začatím terapie a po 5mesiacoch menej priamej terapie podľa Yarussa a Reardon-Reeves (2017) a zhodnotiť, či terapia pozitívne ovplyvnila príznaky zajakavosti u dvoch detí vo veku 3 a 4,8 rokov. Ďalším cieľom bolo zhodnotiť, či sa znížila miera obáv rodičov po terapii. Metódy: Na vylúčenie vývinovej jazykovej poruchy sme použili Korálkový test opakovania pseudoslov a GAPS – subtest opakovanie viet. Na potenciálne odhalenie narušenia zvukovej roviny reči sme zhodnotili zrozumiteľnosť reči meranú Škálou ICS. Prejavy zajakavosti sme identifikovali z rečovej vzorky z uvedených subtestov opakovania viet a pseudoslov, z rozprávania príbehu podľa obrázkovej predlohy (MAIN), z automatizmov, dokončovania viet a z nahrávky spontánnej rečovej vzorky z domáceho prostredia. Na 5bodovej škále sme hodnotili aj mieru obáv rodičov. Rovnako, na 5bodovej škále, rodičia hodnotili aj plynulosť svojho dieťaťa za každý deň v domácom prostredí. Terapeutická metodika Yarussa a Reardon-Reeves (2017) vychádza z multifaktorálneho modelu zajakavosti a pozostáva z dvoch prístupov k terapii zajakavosti u detí v predškolskom a mladšom školskom veku – menej a viac priameho prístupu. V prezentovanom výskume sme využili menej priamu terapiu u dvoch detí vo veku 3 a 4,8 rokov v prvej fáze terapie. Cieľom menej priamej terapie je vytvoriť pre dieťa prostredie podporujúce plynulosť reči. Pre tento účel sa rodičia učia päť komunikačných stratégií. Výsledky: U oboch detí sa po fáze menej priamej terapie znížili neplynulosti reči vo všetkých sledovaných oblastiach. U prvého dieťaťa sa neplynulosti znížili v priemere o 34,11 % a u druhého dieťaťa o 9,13 %. U oboch detí sa znížili obavy rodičov aj hodnotenie neplynulostí v domácom prostredí, ktoré realizovali rodičia. Záver: Adaptovali sme metodiku Yarussa a Reardon-Reeves (2017) na slovenské pomery a overili efektivitu menej priamej terapie na dvoch deťoch. Podľa pilotných výsledkov môžeme povedať, že u týchto dvoch detí bola terapia efektívna, na overenie efektivity menej priamej terapie je však potrebný ešte ďalší výskum, podrobnejšia analýza aktuálne získaných dát a sledovanie dlhodobého efektu terapie.

Introduction: Stuttering is a complex speech disorder, appearing already at preschool age. Despite the fact that spontaneous correction may occur, we consider it important to devote therapy to this disorder already at this age. Objective: We decided to measure and compare stuttering symptoms before and after therapy, thus to determine whether the less-direct stuttering therapy according to Yaruss and Reardon-Reeves (2017) was effective and had a positive effect on stuttering symptoms in two children aged 3 and 4.8 years. We also wanted to determine whether the parents’ concerns decreased after therapy. Methods: Firstly, an examination was conducted to rule out a developmental language disorder or a speech and sound disorder. Dysfluencies were evaluated in speech samples gathered by different speech tasks: non-word and sentence repetition, sentence completion, automatic speech tasks and spontaneous speech recordings (home and MAIN). We also assessed the level of the parents’ concerns on a 5-point scale. Further, on a 5-point scale, parents evaluated their child’s fluency for each day in the home environment. Less-direct therapy (Yaruss and Reardon-Reeves, 2017) is based on a multidisciplinary model of stuttering and consists of two approaches to the therapy of stuttering in children – less direct and more direct. In our research, we used less-direct therapy in two children aged 3 and 4.8 years at the time the therapy started. The aim of less-direct therapy is to create an environment for the child that supports his/her fluency. Parents learn 5 communication strategies. Results: In both children, there was a reduction of dysfluencies in all examined areas. In the case of the first child, dysfluencies decreased by 34.11% and, in the case of the second child, by 9.13%. In both children, the parents’ concerns and the assessment of dysfluencies in the home environment decreased. Conclusion: We adapted the methodology of Yaruss and Reardon-Reeves (2017) to Slovak conditions and verified the effectiveness of less-direct therapy on two children. Based on our results, we can state that the therapy was effective for these two children. However, further research, more thorough analyses of the data and monitoring of the long-term effect of the therapy are needed.

• MeSH
• koktavost * terapie   MeSH
• lidé MeSH
• předškolní dítě MeSH
• řečová terapie metody   MeSH
• Check Tag
• lidé MeSH
• předškolní dítě MeSH
• Publikační typ
• kazuistiky MeSH

Výsledky klinické studie AETHERA ukázaly, že konsolidační terapie brentuximab vedotinem po vysokodávkované chemoterapii a provedení autologní transplantace kmenových hematopoetických buněk signifikantně prodlužuje přežití bez progrese u pacientů s klasickým Hodgkinovým lymfomem. V této multicentrické retrospektivní analýze sedmi hematologických center České republiky jsme analyzovali klinická data z reálné klinické praxe a výsledky léčby u 39 pacientů léčených konsolidační terapií brentuximab vedotinem od ledna 2015 do prosince 2021. Brentuximab vedotin nebyl nemocným podáván v předchozí léčbě lymfomu a pacienti měli nejméně jeden definovaný rizikový faktor pro další relaps. Medián podaných cyklů brentuximab vedotinu byl 8 (1-16), 82 % pacientů dosáhlo během léčby kompletní remise. Medián sledování byl 28 měsíců, dvouleté přežití bez progrese bylo 66,2 % (95% CI 0,52-0,85) a dvouleté celkové přežití 95 % (95% CI 0,82-1,00). Nejčastějším důvodem ukončení léčby bylo kompletní podání 16 léčebných cyklů (20,5 %), relaps/progrese lymfomu (15,4 %) a stejně tak rozvoj symptomatické periferní neuropatie, která byla v různém stupni závažnosti pozorována u 38,5 % pacientů. Naše data potvrzují deklarovanou účinnost a bezpečnost konsolidační terapie brentuximab vedotinem v reálné klinické praxi.

The results from the clinical trial AETHERA showed that consolidation therapy with brentuximab vedotin after high-dose chemotherapy followed by autologous stem cell transplantation increases progression free survival in high-risk patients with relapsed/refractory classic Hodgkin lymphoma. In this multicenter retrospective analysis from seven hematological centers in the Czech republic we have analysed real-life data of 39 patients treated between January 2015 and December 2021. Brentuximab vedotin was not administered in the previous treatment and the patients were at increased risk of subsequent lymphoma relapse with at least one defined risk factor. The median cycles of brentuximab vedotin administered was 8 (1-16), 82 % of the patients achieved complete remission during the treatment. The median follow-up was 28 months, the 2-year progression-free survival and overal survival were 66,2 % (95 % CI 0,52-0,85) and 95 % (95 % CI 0,82-1,00), respectively. The most common reason for treatment discontinuation was completion of 16 cycles administered (20,5 %) relapse/progression of the lymphoma (15,4 %) and symptomatic peripheral neuropathy as well, that was observed in various severity grades in 38,5 % patients overall. Our data have confirmed efficacy and safety of brentuximab vedotin consolidation therapy in the real-life clinical practice.

• MeSH
• brentuximab vedotin aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• chemoterapie konsolidační metody   MeSH
• doba přežití bez progrese choroby MeSH
• Hodgkinova nemoc * diagnóza   farmakoterapie   patologie   MeSH
• indukční chemoterapie metody   MeSH
• klinická studie jako téma MeSH
• lidé MeSH
• nemoci periferního nervového systému etiologie   MeSH
• PET/CT metody   MeSH
• protinádorové látky imunologicky aktivní aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• transplantace hematopoetických kmenových buněk metody   MeSH
• Check Tag
• lidé MeSH

Somatic JAK2 mutations are the main molecular cause of the vast majority of polycythemia vera (PV) cases. According to a recent structural model, the prevalent acquired V617F mutation improves the stability of the JAK2 dimer, thereby enhancing the constitutive JAK2 kinase activity. Germline JAK2 mutations usually do not largely alter JAK2 signaling, although they may modulate the impact of V617F. We found an unusual germline JAK2 mutation L604F in homozygous form in a young PV patient, along with a low allele burden JAK2 V617F mutation, and in her apparently healthy sister. Their father with a PV-like disease had L604F in a heterozygous state, without V617F. The functional consequences of JAK2 L604Fmutation were compared with those induced by V617F in two different in vitro model systems: (i) HEK293T cells were transfected with plasmids for exogenous JAK2-GFP expression, and (ii) endogenous JAK2 modifications were introduced into HeLa cells using CRISPR/Cas9. Both mutations significantly increased JAK2 constitutive activity in transfected HEK293T cells. In the second model, JAK2 modification resulted in reduced total JAK2 protein levels. An important difference was also detected: as described previously, the effect of V617F on JAK2 kinase activity was abrogated in the absence of the aromatic residue F595. In contrast, JAK2 hyperactivation by L604F was only partially inhibited by the F595 change to alanine. We propose that the L604F mutation increases the probability of spontaneous JAK2 dimer formation, which is physiologically mediated by F595. In addition, L604F may contribute to dimer stabilization similarly to V617F.

• MeSH
• HEK293 buňky MeSH
• HeLa buňky MeSH
• Janus kinasa 2 genetika   MeSH
• lidé MeSH
• mutace MeSH
• zárodečné buňky * MeSH
• zárodečné mutace * MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Parkinson's disease (PD) affects the language processes, with a significant impact on the patients' daily communication. We aimed to describe specific alterations in the comprehension of syntactically complex sentences in patients with PD (PwPD) as compared to healthy controls (HC) and to identify the neural underpinnings of these deficits using a functional connectivity analysis of the striatum. A total of 20 patients PwPD and 15 HC participated in the fMRI study. We analyzed their performance of a Test of sentence comprehension (ToSC) adjusted for fMRI. A task-dependent functional connectivity analysis of the striatum was conducted using the psychophysiological interaction method (PPI). On the behavioral level, the PwPD scored significantly lower (mean ± sd: 77.3 ± 12.6) in the total ToSC score than the HC did (mean ± sd: 86.6 ± 8.0), p = 0.02, and the difference was also significant specifically for sentences with a non-canonical word order (PD-mean ± sd: 69.9 ± 14.1, HC-mean ± sd: 80.2 ± 11.5, p = 0.04). Using PPI, we found a statistically significant difference between the PwPD and the HC in connectivity from the right striatum to the supplementary motor area [SMA, (4 8 53)] for non-canonical sentences. This PPI connectivity was negatively correlated with the ToSC accuracy of non-canonical sentences in the PwPD. Our results showed disturbed sentence reading comprehension in the PwPD with altered task-dependent functional connectivity from the right striatum to the SMA, which supports the synchronization of the temporal and sequential aspects of language processing. The study revealed that subcortical-cortical networks (striatal-frontal loop) in PwPD are compromised, leading to impaired comprehension of syntactically complex sentences.

• Publikační typ
• časopisecké články MeSH

Na plynulosť produkcie diskurzu a výskyt dysfluencií v ňom môže vplývať viacero faktorov. Faktory, ktorých vplyv sa zvažuje pri hodnotení jazykovej produkcie, sú vek, vzdelanie a pohlavie, no zatiaľ vieme relatívne málo o vplyve týchto faktorov na výskyt dysfluencií v diskurzoch zdravej dospelej populácie. Preto bolo cieľom nášho výskumu priniesť ucelenejší pohľad na túto problematiku. Vzájomne sme porovnávali výskyt dysfluencií v diskurzoch mužov a žien, v troch vekových a troch vzdelanostných kategóriách, pričom sme pracovali s celkovou vzorkou 182 participantov. Podľa našich výsledkov vek, vzdelanie ani pohlavie nemajú vplyv na celkový výskyt dysfluencií pri produkcii diskurzu, no každý faktor ovplyvňuje výskyt konkrétneho typu dysfluencie. Vek má vplyv na výskyt interjekcií, fonologických a sémantických opráv, ako aj opráv celkovo. Vzdelanie má vplyv na výskyt repetícií častí slov a gramatických opráv. Pohlavie má vplyv na výskyt repetícií slov.

Several factors can affect the fluency of discourse production and the occurrence of disfluencies within it. Mostly the influence on language production of age, education and gender is considered. However, to date, we know relatively little about the influence of these factors on the incidence of disfluencies in the discourses of the healthy adult population. Therefore, the aim of our research was to provide a more comprehensive view of this issue. We compared the incidence of disfluencies in male and female discourses, in three age and three educational categories, working with a total sample of 182 participants. According to our results, age, education, and gender do not affect the overall incidence of disfluencies in discourse production, but each factor affects the incidence of a particular type of disfluency. Age affects the occurrence of interjections, phonological and semantic corrections, as well as corrections in general. Education influences the occurrence of part-word repetitions and grammatical corrections. Gender affects the occurrence of word repetitions.

• MeSH
• koktavost * MeSH
• lidé MeSH
• stupeň vzdělání MeSH
• věkové faktory MeSH
• výzkum MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH

The immune system is important for elimination of residual leukemic cells during acute myeloid leukemia (AML) therapy. Anti-leukemia immune response can be inhibited by various mechanisms leading to immune evasion and disease relapse. Selected markers of immune escape were analyzed on AML cells from leukapheresis at diagnosis (N = 53). Hierarchical clustering of AML immunophenotypes yielded distinct genetic clusters. In the absence of DNMT3A mutation, NPM1 mutation was associated with decreased HLA expression and low levels of other markers (CLIP, PD-L1, TIM-3). Analysis of an independent cohort confirmed decreased levels of HLA transcripts in patients with NPM1 mutation. Samples with combined NPM1 and DNMT3A mutations had high CLIP surface amount suggesting reduced antigen presentation. TIM-3 transcript correlated not only with TIM-3 surface protein but also with CLIP and PD-L1. In our cohort, high levels of TIM-3/PD-L1/CLIP were associated with lower survival. Our results suggest that AML genotype is related to blast immunophenotype, and that high TIM-3 transcript levels in AML blasts could be a marker of immune escape. Cellular pathways regulating resistance to the immune system might contribute to the predicted response to standard therapy of patients in specific AML subgroups and should be targeted to improve AML treatment.

• MeSH
• akutní myeloidní leukemie * diagnóza   genetika   MeSH
• antigeny CD274 genetika   MeSH
• biologické markery MeSH
• buněčný receptor 2 viru hepatitidy A genetika   MeSH
• DNA methyltransferasa 3A * genetika   MeSH
• lidé MeSH
• mutace MeSH
• nukleofosmin * genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: The German Hodgkin Study Group's HD18 trial established the safety and efficacy of PET-guided eBEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone in escalated doses) for the treatment of advanced-stage Hodgkin lymphoma. However, because of a protocol amendment during the enrolment period (June 1, 2011) that changed standard treatment from eight to six cycles, the results of the HD18 trial have been partially immature. We report a prespecified 5-year follow-up analysis of the completed HD18 trial. METHODS: HD18 was an international, open-label, randomised, phase 3 trial done in 301 hospitals and private practices in five European countries. Patients aged 18-60 years with newly diagnosed, advanced-stage Hodgkin lymphoma and an Eastern Cooperative Oncology Group performance status of 0-2 were recruited. After receiving an initial two cycles of eBEACOPP (1250 mg/m2 intravenous cyclophosphamide [day 1], 35 mg/m2 intravenous doxorubicin [day 1], 200 mg/m2 intravenous etoposide [day 1-3], 100 mg/m2 oral procarbazine [day 1-7], 40 mg/m2 oral prednisone [day 1-14], 1·4 mg/m2 intravenous vincristine [day 8], and 10 mg/m2 intravenous bleomycin [day 8]), patients underwent a contrast-enhanced CT and PET scan (PET-2). Patients with positive PET-2 were randomly assigned to receive standard therapy (an additional six cycles of eBEACOPP; ie, eight cycles in total) or experimental therapy (an additional six cycles of eBEACOPP plus 375 mg/m2 intravenous rituximab; ie, eight cycles in total) until June 1, 2011. After June 1, 2011, all patients with positive PET-2 were assigned to the updated standard therapy with an additional four cycles of eBEACOPP (ie, six cycles in total). Patients with negative PET-2 were randomly assigned (1:1) to receive standard therapy (an additional six cycles of eBEACOPP [ie, eight cycles in total] until June 1, 2011; an additional four cycles of eBEACOPP [ie, six cycles in total] after June 1, 2011) or experimental therapy (an additional two cycles of eBEACOPP; ie, four cycles in total). Randomisation was done centrally with the minimisation method, including a random component, stratified by centre, age, stage, international prognostic score, and sex. The primary endpoint was progression-free survival. HD18 aimed to improve 5-year progression-free survival by 15% in the PET-2-positive intention-to-treat cohort and to exclude inferiority of 6% or more in 5-year progression-free survival in the PET-2-negative per-protocol population. This study is registered with ClinicalTrials.gov, NCT00515554, and is completed. FINDINGS: Between May 14, 2008, and July 18, 2014, 2101 patients were enrolled and 1945 were assigned to a treatment group according to their PET-2 result. In the PET-2-positive cohort, with a median follow-up of 73 months (IQR 59 to 94), 5-year progression-free survival was 89·9% (95% CI 85·7 to 94·1) in 217 patients assigned to eight cycles of eBEACOPP before the protocol amendment and 87·7% (83·1 to 92·4) in 217 patients assigned to eight cycles of rituximab plus eBEACOPP (p=0·40). Among 506 patients who received six cycles of eBEACOPP after the protocol amendment, 5-year progression-free survival was 90·1% (95% CI 87·2 to 92·9), with a median follow-up of 58 months (IQR 39 to 66). In the PET-2-negative cohort, with a median follow-up of 66 months (IQR 54 to 85) in the combined pre-amendment and post-amendment groups, 5-year progression-free survival was 91·2% (95% CI 88·4 to 93·9) in 446 patients who received eight or six cycles of eBEACOPP and 93·0% (90·6 to 95·4) in 474 patients who received four cycles of eBEACOPP (difference 1·9% [95% CI -1·8 to 5·5]). In the subgroup of PET-2-negative patients randomly assigned after protocol amendment, 5-year progression-free survival was 90·9% (95% CI 86·8 to 95·1) in 202 patients assigned to receive six cycles of eBEACOPP and 91·0% (86·6 to 95·5) in 200 patients assigned to receive four cycles of eBEACOPP (difference 0·1% [-5·9 to 6·2]). INTERPRETATION: Long-term follow-up confirms the efficacy and safety of PET-2-guided eBEACOPP in patients with advanced-stage Hodgkin lymphoma. The reduction from eight to four cycles of eBEACOPP represents a benchmark in the treatment of early-responding patients, who can now be potentially cured with a short and safe treatment approach. FUNDING: Deutsche Krebshilfe, Swiss State Secretariat for Education, Research and Innovation SERI (Switzerland), and Roche Pharma. TRANSLATION: For the German translation of the abstract see Supplementary Materials section.

• MeSH
• bleomycin aplikace a dávkování   MeSH
• doba přežití bez progrese choroby MeSH
• dospělí MeSH
• doxorubicin aplikace a dávkování   MeSH
• etoposid aplikace a dávkování   MeSH
• Hodgkinova nemoc farmakoterapie   mortalita   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• následné studie MeSH
• pozitronová emisní tomografie MeSH
• protokoly antitumorózní kombinované chemoterapie terapeutické užití   MeSH
• rituximab aplikace a dávkování   MeSH
• staging nádorů MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH

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/m2 (days 1 and 15), bleomycin 10 mg/m2 (days 1 and 15), vinblastine 6 mg/m2 (days 1 and 15), and dacarbazine 375 mg/m2 (days 1 and 15), repeated on day 29. The escalated BEACOPP dosing regimen was cyclophosphamide 1250 mg/m2 (day 1), doxorubicin 35 mg/m2 (day 1), etoposide 200 mg/m2 (days 1-3), procarbazine 100 mg/m2 (days 1-7), prednisone 40 mg/m2 (days 1-14), vincristine 1·4 mg/m2 (day 8; maximum 2 mg), and bleomycin 10 mg/m2 (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.

• MeSH
• bleomycin aplikace a dávkování   terapeutické užití   MeSH
• cyklofosfamid aplikace a dávkování   terapeutické užití   MeSH
• dakarbazin aplikace a dávkování   terapeutické užití   MeSH
• doba přežití bez progrese choroby MeSH
• dospělí MeSH
• doxorubicin aplikace a dávkování   terapeutické užití   MeSH
• etoposid aplikace a dávkování   terapeutické užití   MeSH
• Hodgkinova nemoc farmakoterapie   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• následné studie MeSH
• prednison aplikace a dávkování   terapeutické užití   MeSH
• prokarbazin aplikace a dávkování   terapeutické užití   MeSH
• protokoly antitumorózní kombinované chemoterapie terapeutické užití   MeSH
• sekundární malignity epidemiologie   MeSH
• staging nádorů metody   MeSH
• vinblastin aplikace a dávkování   terapeutické užití   MeSH
• vinkristin aplikace a dávkování   terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH
• Geografické názvy
• Německo MeSH