BACKGROUND: Whole-body magnetic resonance imaging (wbMRI) allows general assessment of systemic cancers including lymphomas without radiation burden. AIM: To evaluate the diagnostic performance of wbMRI in the staging of diffuse large B-cell lymphoma (DLBCL), determine the value of individual MRI sequences, and assess patients' concerns with wbMRI. METHODS: In this single-center prospective study, adult patients newly diagnosed with systemic DLBCL underwent wbMRI on a 3T scanner [diffusion weighted images with background suppression (DWIBS), T2, short tau inversion recovery (STIR), contrast-enhanced T1] and fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) (reference standard). The involvement of 12 nodal regions and extranodal sites was evaluated on wbMRI and PET/CT. The utility of wbMRI sequences was rated on a five-point scale (0 = not useful, 4 = very useful). Patients received a questionnaire regarding wbMRI. RESULTS: Of 60 eligible patients, 14 (23%) were enrolled and completed the study. The sensitivity of wbMRI in the nodal involvement (182 nodal sites) was 0.84, with 0.99 specificity, positive predictive value of 0.96, negative predictive value of 0.97, and 0.97 accuracy. PET/CT and wbMRI were concordant both in extranodal involvement (13 instances) and staging (κ = 1.0). The mean scores of the utility of MRI sequences were 3.71 ± 0.73 for DWIBS, 2.64 ± 0.84 for T1, 2.14 ± 0.77 for STIR, and 1.29 ± 0.73 for T2 (P < 0.0001). Patients were mostly concerned about the enclosed environment and duration of the MRI examination (27% of patients). CONCLUSION: The wbMRI exhibited excellent sensitivity and specificity in staging DLBCL. DWIBS and contrast-enhanced T1 were rated as the most useful sequences. Patients were less willing to undergo wbMRI as a second examination parallel to PET/CT, especially owing to the long duration and the enclosed environment.

• Publikační typ
• časopisecké články MeSH

This study aimed to evaluate the ability of selected microRNAs as biomarkers of atrial fibrillation (AF) in ischemic stroke patients in comparison with other established biochemical biomarkers. A prospective case-control study of consecutive ischemic stroke patients with AF admitted to a comprehensive stroke center was conducted. The control group consisted of patients with ischemic stroke with no AF detected on prolonged (at least 3 weeks) Holter ECG monitoring. As potential biomarkers of AF, we analyzed the plasma levels of microRNAs (miR-21, miR-29b, miR-133b, miR-142-5p, miR-150, miR-499, and miR-223-3p) and 13 biochemical biomarkers at admission. The predictive accuracy of biomarkers was assessed by calculating the area under the receiver operating characteristic curve. The data of 117 patients were analyzed (61 with AF, 56 with no AF, 46% men, median age 73 years, median National Institutes of Health Stroke Scale 6). Biochemical biomarkers (N-terminal pro-B-type natriuretic peptide [NT-proBNP], high-sensitivity cardiac troponin I, fibrinogen, C-reactive protein, eGFR, and total triglycerides) were significantly associated with AF. NT-proBNP had the best diagnostic performance for AF with area under the receiver operating characteristic curve 0.92 (95%, CI 0.86-0.98); a cutoff value of >528 ng/L had a sensitivity of 79% and a specificity of 97%. None of the other biomarkers, including microRNAs, was associated with AF. Conventional biochemical biomarkers (NT-proBNP, high-sensitivity cardiac troponin I, fibrinogen, C-reactive protein, eGFR, and triglycerides), but not microRNAs (miR-21, miR-29b, miR-133b, miR-142-5p, miR-150, miR-499, and miR-223-3p) were significantly associated with AF in our ischemic stroke cohort.

• MeSH
• biologické markery * krev   MeSH
• C-reaktivní protein analýza   MeSH
• fibrilace síní * krev   diagnóza   genetika   MeSH
• ischemická cévní mozková příhoda * krev   diagnóza   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mikro RNA * krev   MeSH
• natriuretický peptid typu B krev   MeSH
• peptidové fragmenty krev   MeSH
• prospektivní studie MeSH
• ROC křivka MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH

BACKGROUND: Dabigatran directly inhibits thrombin and is used in primary and secondary stroke prevention in individuals with nonvalvular atrial fibrillation. The prodrug dabigatran etexilate is absorbed by enteral P-glycoprotein (ABCB1) and then activated by hepatic and intestinal carboxylesterases (CES1) to produce active metabolites. Variations in dabigatran metabolism because of genetics may affect concentration levels and clinical outcomes. STUDY QUESTION: We conducted a study to assess how polymorphisms in the CES1 (rs2244613) and ABCB1 (rs4148738) genes affect the through plasma level (c min ) of dabigatran and its correlation to clinical outcomes. STUDY DESIGN: Retrospective multicentric study of consecutive patients on dabigatran therapy. Examination of CES1 rs2244613 and ABCB1 rs4148738 polymorphisms, c min 12 hours after administration, clinical follow-up (ischemic stroke, major or clinically relevant hemorrhage, myocardial infarction, other thromboembolism, and death). MEASURES AND OUTCOMES: A total of 432 patients received treatment for an average of 19.78 months (SD of 20.165). The sex distribution of the patients was 56.5% male, and the average age was 67.56 years (SD of 14.7). The ABCB1 variant genotype was present in 67.8% of patients, whereas 37.5% carried the CES1 polymorphism. RESULTS: Compared with wild-type patients, patients with the CES1 variant had significantly lower dabigatran plasma levels (with a mean difference of 16.986; 95% confidence interval, 5.794-28.178 ng/mL, P = 0.003). We also found a significant risk of major bleeding in patients carrying the ABCB1 rs4148738 allele (hazard ratio = 1.99, confidence interval 95% 1.10 to 3.59, P = 0.024). CONCLUSIONS: The CES1 variant genotype rs2244613 is closely linked with reduced c min of dabigatran. Carriers of the ABCB1 rs4148738 polymorphism exhibit a tendency toward higher plasma levels of dabigatran, which leads to a significantly increased risk of bleeding.

• MeSH
• antitrombiny * škodlivé účinky   krev   farmakokinetika   aplikace a dávkování   MeSH
• dabigatran * škodlivé účinky   farmakokinetika   krev   aplikace a dávkování   MeSH
• fibrilace síní farmakoterapie   genetika   komplikace   krev   MeSH
• ischemická cévní mozková příhoda * prevence a kontrola   genetika   krev   MeSH
• jednonukleotidový polymorfismus MeSH
• karboxylesterhydrolasy * genetika   krev   MeSH
• krvácení * chemicky indukované   krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• P-glykoproteiny * genetika   MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

Ibrutinib revolutionized therapy for relapsed/refractory (R/R) mantle cell lymphoma (MCL). Real-world data on the outcome of unselected patients are still limited. We analyzed 77 R/R MCL patients receiving ibrutinib with at least one prior systemic anti-lymphoma therapy. After a median follow-up of 14.0 months, 56 patients relapsed/progressed, and 45 died. The overall response rate was 66%, with 31% of complete metabolic remissions on PET/CT. The median progression-free and overall survival (OS) rates were 10.3 and 23.1 months, respectively. The median OS from ibrutinib failure was 3.7 months. High proliferation rate by Ki67 (≥ 30%) and two or more previous therapy lines both negatively correlated with outcome (HR = 2.2, p = 0.04, and HR = 2.06, p = 0.08, respectively). Female gender borderline correlated with better outcome (HR = 0.53, p = 0.08). In multivariate analysis, Ki67 and response to ibrutinib both correlated with OS (p < 0.05). Importantly, ibrutinib appeared to better control nodal and extranodal lymphoma than bone marrow (BM) involvement. From 20 patients with detectable BM infiltration (before ibrutinib initiation) achieving complete (n = 13) or partial (n = 7) metabolic remission, none achieved remission in BM. We confirmed good efficacy of ibrutinib in unselected heavily pre-treated MCL patients. Our findings support the use of a combination of ibrutinib and rituximab in patients with BM involvement.

• MeSH
• antigen Ki-67 MeSH
• dospělí MeSH
• lidé MeSH
• lymfom z plášťových buněk * patologie   MeSH
• PET/CT MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• Geografické názvy
• Česká republika 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
• doba přežití bez progrese choroby MeSH
• Hodgkinova nemoc * diagnóza   farmakoterapie   patologie   MeSH
• indukční chemoterapie metody   MeSH
• klinická studie jako téma MeSH
• konsolidační chemoterapie metody   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

• Publikační typ
• abstrakt z konference MeSH

Přinášíme kazuistiku mladé pacientky s terapeuticky refrakterním difúzním velkobuněčným B-lymfomem s důrazem na spolupráci mezi hemato-onkology a lékaři paliativního týmu ve Všeobecné fakultní nemocnici (VFN) v Praze. Na konkrétním příkladu demonstrujeme roli hematoonkologa, který s pacientem probírá terapeutický plán a možné komplikace léčby, a také mapuje rodinné zázemí konkrétního nemocného, a přínos paliativního týmu u pacientky ve složité sociální situaci a non-compliantní k terapii. Přínos paliativního týmu u pacientky ve složité sociální situaci a non-compliantní k terapii spočíval v efektivní intervenci, která nejen vytvořila důvěru mezi pacientkou, paliativním týmem a ošetřujícími hemato-onkology, ale sekundárně přispěla k celkově zlepšené komunikaci, vyšší adherenci k léčbě, účinné sociální podpoře a péči, která byla v souladu s hodnotami a preferencemi pacientky.

Introduction: We analyzed the incidence, risk factors of central nervous system (CNS) relapse, and outcome of CNS involvement in patients with peripheral T-cell lymphomas (PTCL) from the Czech Lymphoma Study Group Registry NiHiL (Clinical Trial gov. NCT03199066). Materials and Methods: Out of 1,040 patients with PTCL, we identified 29 patients (2.79%) with CNS involvement: 2 patients with primary CNS T cell lymphoma, 11 patients with CNS and systemic disease at diagnosis, and 16 patients (1.54%) at CNS relapse. The most common histology with CNS disease was PTCL, not otherwise specified. Progression-free survival (PFS) was defined as the time interval from diagnosis to progression or death. PFS-2 was defined as the interval from the date of a new relapse until the next relapse. Results: Patients with testicular involvement received intrathecal prophylaxis with methotrexate. High-dose methotrexate-based treatment was administered in 44.8% of patients with CNS disease. Median follow-up was 71.3 months. The difference between the median PFS of 1,027 patients without initial CNS disease (32.6 months) and 11 patients with initial CNS and systemic disease (4.8 months) was significant (p = 0.04). The difference between the median PFS2 in CNS relapses (10.1 months) and 493 relapses outside of CNS (9.1 months) was not significant (p = 0.6). Risk factors for CNS relapses included the following: involvement of more than one extranodal site (p = 0.008), soft tissue involvement (p = 0.003), testicular involvement (p = 0.046), and the presence of B symptoms (p = 0.035). The difference between the median OS of 1,027 patients without initial CNS disease (46.0 months) and 11 patients with initial CNS and systemic disease (18.2 months) was significant (p = 0.02). The median OS2 in CNS relapses was 11.8 months and that in relapses outside of CNS was 21.3 months. CNS involvement was not associated with a significantly worse OS compared to relapsed/refractory patients without CNS involvement (p = 0.1). Conclusions: The incidence of CNS disease at the time of diagnosis and at relapse in PTCL is low and usually associated with other systemic involvement. The prognosis of PTCL with initial CNS involvement is significantly worse when compared to patients without CNS disease at diagnosis. The outcome of CNS relapse is comparable with relapsed PTCL outside of CNS. The optimal treatment is not defined yet.

• Publikační typ
• časopisecké články MeSH

OBJECTIVES: Polatuzumab vedotin with bendamustine and rituximab (Pola-BR) was approved for treatment of transplant-ineligible patients with relapsed/refractory DLBCL (R/R DLBCL). However, the number of patients treated in the GO29365 trial including the extension cohort was limited, and more data evaluating the efficacy of this treatment regimen is needed. METHODS: We analyzed 21 patients with R/R DLBCL to determine real-life efficacy and safety of Pola-BR regimen. Data of all patients entered the database of the NiHiL project (NCT03199066). RESULTS: Median overall survival was 8.7 months, and progression-free survival 3.8 months. The overall response rate was 33%. Grade 3-4 neutropenia was detected in 29%, thrombocytopenia in 38%, anemia in 19%, infections in 24% cases, and peripheral neuropathy in 5%. Discontinuation of treatment was caused by progression in 50%, adverse events in 31%, and intended bridging to CAR-T therapy in 19%. CONCLUSION: Although the outcome of patients is worse than in GO29365 trial, the use of Pola-BR regimen in the real world demonstrates tolerable toxicity profile and efficacy in transplant-ineligible patients with R/R DLBCL. Moreover, this regimen might represent a perspective option as a bridge to CAR-T therapy.

• MeSH
• bendamustin hydrochlorid MeSH
• chimerické antigenní receptory * MeSH
• difúzní velkobuněčný B-lymfom * diagnóza   farmakoterapie   MeSH
• imunokonjugáty * MeSH
• lidé MeSH
• monoklonální protilátky MeSH
• nehodgkinský lymfom * farmakoterapie   MeSH
• protokoly protinádorové kombinované chemoterapie škodlivé účinky   MeSH
• rituximab MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH

Předkládáme kazuistiku 72leté ženy, která se primárně dostavila do neurologické ambulance pro levostrannou brachiofaciální parézu, dysartrii a bolest hlavy. MR mozku odhalila jako příčinu neurologického deficitu ložisko frontálně vpravo s radiologickou charakteristikou typickou pro lymfom CNS. Biopsie tohoto ložiska byla diagnosticky nevýtěžná s průkazem nespecifických zánětlivých změn. Kontrolní MR mozku prokázala téměř úplné vymizení vstupně zachyceného ložiska a dvě nová ložiska, uložená v obou hemisférách, se stejnou radiologickou charakteristikou jako vstupně pozorované ložisko. Referujeme tedy případ tzv. sentinel lesion, a to za okolností, kdy jsme se před zákrokem zdrželi podání kortikoidů. Rebiopsie nově zachycených ložisek již byla s histologickým průkazem buněk lymfomu a umožnila zahájení cílené terapie. V článku komentujeme jednotlivé kroky v diagnostice. Zmiňujeme mj. indikace a rizika mozkové biopsie.

We show a case study of a 72-years old woman who firstly presented with left side brachiofacial paresis, dysarthria and headache. MR brain scan revealed a lesion in right frontal lobe with radiological findings typical for a brain lymphoma. Biopsy of this lesion was diagnostically inconclusive with unspecific inflammatory changes. MR scan performed after the biopsy showed substantial regression of the firstly found lesion and 2 new lesions, with similar radiological characteristics as the one which regressed, each one in a different hemisphere. We therefore present a case of a sentinel lesion. In our case no corticoid therapy was given before the surgery. Rebiopsy of one of the newly found lesions proved the presence of lymphoma cells and chemotherapy was initiated. We have included a commentary of each diagnostic step. We also comment on indications and risks of brain biopsy.

• Klíčová slova
• rebiopsie,
• MeSH
• biopsie MeSH
• lidé MeSH
• lymfom chirurgie   diagnóza   MeSH
• nádory centrálního nervového systému * chirurgie   dietoterapie   MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH