BACKGROUND: In chronic lymphocytic leukemia (CLL), changes in the peripheral blood lymphocyte subsets play an important role in disease progression and infectious complications. The impact of chemoimmunotherapy (CIT) on these changes has not been extensively studied METHODS: We used multi-color flow cytometry, to prospectively measure absolute and relative numbers of CD4+ and CD8+ T-cells and their subsets in 45 patients with indolent untreated CLL, 86 patients indicated for first-line treatment, and 34 healthy controls. In 55 patients, we analyzed the impact of CIT RESULTS: CLL patients had a significant increase in most cell populations in comparison to controls. Progression of CLL was characterized by significantly elevated counts with the exception of a lower percentage of naïve T-cells. After treatment, the percentage of naïve T-cells further decreased at the expense of effector memory T-cells (TEM). In patients with indolent CLL, higher percentages of naïve CD4+ (p = 0.0026) and naïve CD8+ (p = 0.023) T-cells were associated with a longer time to first treatment (TTFT). The elevation of CD4+ central memory T-cells (TCM) (p = 0.27) and TEM (p = 0.003) counts and a higher percentage of CD4+ TEM (p = 0.0047), were linked with shorter TTFT. In treated patients, increased regulatory T-cells count was associated with shorter time to next treatment (TTNT) (p = 0.042), while higher CD4+ TCM count with shorter TTNT (p = 0.035) and shorter overall survival (p = 0.041). CONCLUSION: Our results indicate that naïve cell depletion and CD4+ TCM and TEM increases are detrimental to CLL patients' prognosis.
- Klíčová slova
- venetoklax, obinutuzumab,
- MeSH
- biologická terapie * metody MeSH
- časové faktory * MeSH
- chronická lymfatická leukemie * diagnóza farmakoterapie MeSH
- kombinovaná farmakoterapie škodlivé účinky MeSH
- lidé MeSH
- přežití po terapii bez příznaků nemoci MeSH
- senioři MeSH
- syndrom nádorového rozpadu farmakoterapie komplikace prevence a kontrola MeSH
- Check Tag
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- práce podpořená grantem MeSH
Idelalisib (idela), a phosphatidylinositol 3-kinase inhibitor, and ibrutinib, a Bruton tyrosine kinase inhibitor, were the first oral targeted agents approved for relapsed/refractory (R/R) chronic lymphocytic leukaemia (CLL). However, no randomised trials of idelalisib plus rituximab (R-idela) versus ibrutinib have been conducted. Therefore, we performed a real-world retrospective analysis of patients with R/R CLL treated with R-idela (n = 171) or ibrutinib (n = 244). The median age was 70 versus 69 years, with a median of two previous lines. There was a trend towards higher tumour protein p53 (TP53) aberrations and complex karyotype in the R-idela group (53% vs. 44%, p = 0.093; 57% vs. 46%, p = 0.083). The median progression-free survival (PFS) was significantly longer with ibrutinib (40.5 vs. 22.0 months; p < 0.001); similarly to overall survival (OS; median 54.4 vs. 37.7 months, p = 0.04). In multivariate analysis, only PFS but not OS remained significantly different between the two agents. The most common reasons for treatment discontinuation included toxicity (R-idela, 39.8%; ibrutinib, 22.5%) and CLL progression (27.5% vs. 11.1%). In conclusion, our data show significantly better efficacy and tolerability of ibrutinib over R-idela in patients with R/R CLL treated in routine practice. The R-idela regimen may still be considered a reasonable option in highly selected patients without a suitable treatment alternative.
- MeSH
- chronická lymfatická leukemie * MeSH
- lidé MeSH
- recidiva MeSH
- registrace MeSH
- retrospektivní studie MeSH
- rituximab MeSH
- senioři MeSH
- Check Tag
- lidé MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Patients with chronic lymphocytic leukemia (CLL) have a high risk of poor outcomes related to coronavirus disease 2019 (COVID-19). This multicenter cohort study evaluated the impact of COVID-19 infection on the population of CLL patients in the Czech Republic. Between March 2020 and May 2021, 341 patients (237 males) with CLL and COVID-19 disease were identified. The median age was 69 years (range 38-91). Out of the 214 (63%) patients with the history of therapy for CLL, 97 (45%) were receiving CLL-directed treatment at diagnosis of COVID-19: 29% Bruton tyrosine kinase inhibitor (BTKi), 16% chemoimmunotherapy (CIT), 11% Bcl-2 inhibitor, and 4% phosphoinositide 3-kinase inhibitor. Regarding the severity of COVID-19, 60% pts required admission to the hospital, 21% pts were admitted to the intensive care unit (ICU), and 12% received invasive mechanical ventilation. The overall case fatality rate was 28%. Major comorbidities, age over 72, male gender, CLL treatment in history, CLL-directed treatment at COVID-19 diagnosis were associated with increased risk of death. Of note, concurrent therapy with BTKi compared to CIT was not associated with better outcome of COVID-19.
- MeSH
- chronická lymfatická leukemie * farmakoterapie epidemiologie MeSH
- COVID-19 * komplikace MeSH
- dospělí MeSH
- fosfatidylinositol-3-kinasy MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- testování na COVID-19 MeSH
- Check Tag
- dospělí MeSH
- 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
- Geografické názvy
- Česká republika MeSH
Autoři prezentují dva případy, u kterých byla provedena UZ navigovaná punkce lymfatické uzliny s následným podáním olejové kontrastní látky, tzv. intranodální lymfografie neboli lymfangiografie. U prvního pacienta se jednalo o chylózní ascites, u druhého pacienta o spontánní pravostranný chylothorax. Význam lymfografie byl v průkazu extravazace lymfy, vyvolání aseptického zánětu vedoucího k fibróze a následně zástavě sekrece lymfy do pleurální nebo břišní dutiny. Intranodální lymfografie v současnosti nahrazuje klasickou pedální lymfografii, protože vede ke zkrácení celkové délky vyšetření a není nutná složitá preparace se zavedením jehly do mízní cévy na dorzu nohy.
The authors report two cases in which ultrasound-guided lymph node puncture with administration of oil contrast agent, so-called intranodal lymphography (lymphangiography), was performed. One patient was treated for chylous ascites, the other patient presented for right-sided chylothorax. The reason for lymphangiography was to demonstrate lymphatic extravasation and to induce aseptic inflammation leading to fibrosis with subsequent cessation of lymph secretion into the pleural or abdominal cavity. Intranodal lymphography replaces conventional bipedal lymphography because it reduces the duration of the examination and does not require difficult preparation and insertion of a needle into lymphatic vessel at the dorsum ofthefoot.
- MeSH
- chylotorax diagnostické zobrazování MeSH
- chylózní ascites diagnostické zobrazování MeSH
- folikulární lymfom diagnostické zobrazování komplikace MeSH
- jehly škodlivé účinky MeSH
- komorbidita MeSH
- kontrastní látky aplikace a dávkování škodlivé účinky MeSH
- lidé MeSH
- lymfatické uzliny diagnostické zobrazování patologie MeSH
- lymfografie * dějiny klasifikace metody přístrojové vybavení škodlivé účinky MeSH
- punkce metody přístrojové vybavení škodlivé účinky MeSH
- senioři MeSH
- ultrasonografie MeSH
- Check Tag
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- práce podpořená grantem MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
Liquid-liquid extraction methods are widely used for sample treatment in bioanalysis, although their implementation poses a common speed-limiting step in the analytical process when fast separation and detection methods such as UHPLC-MS are used. This study aimed to develop high-throughput salting-out assisted liquid-liquid extraction on a 96-well plate in combination with fast LC-MS analysis of ibrutinib and its active metabolite PCI-45227 (dihydrodiol ibrutinib) in human serum. A specially designed 3D printed extraction device developed in our laboratory allowed for the precise and rapid collection of the organic phase from the 96-well plate using a multichannel pipette, without the risk of aspiration of the bottom aqueous layer. The application of this device significantly accelerated sample preparation and allowed the processing of up to 96 samples in 1 h. The method was successfully validated according to EMA guidelines in the concentration range of 0.1-200 ng/mL for both analytes, providing lower limit of quantification at 100 pg/mL. The intra-day accuracy for IBT was in the range of - 1.67-5.67 %, while the inter-day accuracy was in the range of 0.20-6.90 %. The intra-day precision for IBT was in the range of 3.20-4.37 % and 3.13-4.73 % for the inter-day measurement. PCI-45227 showed intra-day accuracy in the range of - 11.2-3.71 % and the inter-day accuracy in the range of - 5.76-0.92 %. The intra-day precision for PCI was in the range of 3.49-7.64 % and 3.63-8.61 % for the measurement between days. In addition to increasing the speed of sample preparation, this method also offers low consumption of the sample and extraction solvent and can be utilized for other similar small-volume in-well plate extractions where organic solvents of lower density than water are used. The method was successfully applied to the analysis of serum samples (n = 5) of patients with chronic lymphoblastic leukaemia at the trough level (ibrutinib concentration range: 1.63-3.78 ng/mL, PCI-45227 concentration range: 1.84-14.02 ng/mL) and 2 h postdose (ibrutinib concentration range: 7.34-89.0 ng/mL, PCI-45227 concentration range: 5.64-124 ng/mL).
- MeSH
- 3D tisk MeSH
- adenin analogy a deriváty MeSH
- extrakce kapalina-kapalina metody MeSH
- koronární angioplastika * MeSH
- lidé MeSH
- piperidiny MeSH
- pyrazoly MeSH
- rozpouštědla MeSH
- tandemová hmotnostní spektrometrie * metody MeSH
- vysokoúčinná kapalinová chromatografie metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Chronická lymfocytární leukemie (CLL) je nejčastější leukemií dospělých v euroamerické populaci a bývá často komplikována autoimunitními cytopeniemi. U nemocných s anémií a trombocytopenií jsou jednou z možných příčin autoimunitní hemolytická anémie (AIHA) a imunitní trombocytopenie (ITP), vzácně také čistá aplázie červené řady (PRCA). Posledních několik let máme při léčbě CLL k dispozici nové cílené perorální inhibitory, jejichž použití významně zlepšilo prognózu nemocných. Naše kazuistické sdělení popisuje úspěšné podání agonisty trombopoetinového receptoru eltrombopagu před cílenou terapií inhibitorem Brutonovy tyrosinkinázy ibrutinibem u nemocné se sekundární ITP.
Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in Euro-American population and is often complicated by autoimmune cytopenias. In patients with anemia and thrombocytopenia, one of the possible causes is autoimmune hemolytic anemia (AIHA), immune thrombocytopenia (ITP), and rarely pure red cell aplasia (PRCA). For the last few years, oral targeted inhibitors have been available for the treatment of CLL. The use of these molecules has significantly improved the prognosis of patients. Our case report describes the successful administration of thrombopoietin receptor agonist eltrombopag before targeted therapy with the Bruton tyrosine kinase inhibitor ibrutinib in a patient with secondary ITP.
- Klíčová slova
- ibrutinib, eltrombopag, agonisté trombopoetinového receptoru,
- MeSH
- chronická lymfatická leukemie diagnóza komplikace MeSH
- lidé MeSH
- senioři MeSH
- trombocytopenie * diagnóza etiologie terapie MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
High doses of corticosteroids in combination with rituximab remain an alternative in the treatment in relapsed or refractory chronic lymphocytic leukaemia (CLL) in the current era of targeted therapies. This study retrospectively evaluates the efficacy of an RCD (rituximab, cyclophosphamide and dexamethasone) regimen in the treatment of 51 patients with relapsed CLL (median age, 72 years). Unfavourable prognostic features, such as Rai stage III/IV, unmutated IGHV, del11q, TP53 mutation/deletion, complex karyotype and bulky lymphadenopathy, were frequent. The overall response or complete remission was of 57% and 7%, respectively, and the median progression-free survival (PFS) was of 12.3 months, median time to next treatment 23.1 months and median overall survival 39.2 months. Significant independent predictors of shorter PFS were TP53 deletion/mutation, advanced Rai stage and ≥2 previous lines of treatment. The incidence of neutropenia grade ≥ 3 was of 13%. Serious (CTCAE grade 3-5) infections were found in 20% of patients. Steroid-induced diabetes or diabetes decompensation occurred in 20% patients. Treatment-related adverse events resulted in RCD dose reduction in 35% of patients. In comparison with a historical R-Dex patient group, the treatment response and/or toxicity in our group was largely similar. However, the substantial differences in the baseline clinical characteristics of the groups may affect this comparison. In conclusion, the RCD regimen is an active, time-limited therapeutic strategy for elderly patients with relapsed CLL. Further, the results of our analysis indicate that the addition of cyclophosphamide to the R-Dex regimen maintains a similar efficacy, even after 50% reduction in the dexamethasone dose.
- MeSH
- chronická lymfatická leukemie farmakoterapie genetika patologie MeSH
- cyklofosfamid aplikace a dávkování MeSH
- dexamethason aplikace a dávkování MeSH
- diabetes mellitus chemicky indukované epidemiologie MeSH
- doba přežití bez progrese choroby MeSH
- indukce remise MeSH
- infekce epidemiologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- lokální recidiva nádoru farmakoterapie genetika patologie MeSH
- míra přežití MeSH
- nádorový supresorový protein p53 genetika MeSH
- neutropenie chemicky indukované epidemiologie MeSH
- protokoly antitumorózní kombinované chemoterapie terapeutické užití MeSH
- retrospektivní studie MeSH
- rituximab aplikace a dávkování MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- staging nádorů MeSH
- vysazování léků MeSH
- výsledek terapie 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
