Pacienti s chronickou myelocytovou leukémiou (CML) v chronickej fáze choroby majú pri liečbe inhibítormi tyrozínových kináz očakávanú dĺžka života približujúcu sa veku prežívania bežnej populácie. Napriek týmto pokrokom zostáva pre hematológov veľkou výzvou určenie optimálnej liečebnej stratégie pre zriedkavé, pokročilé ochorenie – vznikajúce v podobe primárnej alebo terapiou indukovanej a spojené s klonovou evolúciou. Pokročilé ochorenie má pochopiteľne pestrejšie klinické prejavy a prináša aj niektoré neobvyklé a často i život ohrozujúce situácie. Popisujeme zriedkavý prípad pokračujúcej klinickej progresie CML počas liečby inhibítormi tyrozínových kináz so závažnou hemoragickou manifestáciou pri blastovom zvrate a potransplantačným návratom choroby. Je tiež doplnený prehľad niektorých publikovaných prác z tejto oblasti.
Patients with chronic myeloid leukaemia (CML) in chronic phase have a life expectancy similar to the general population when treated with tyrosine kinase inhibitors. Despite these improvements, the major challenge for haematologists is to determine the optimal treatment approach in advanced CML phases (primary or therapy-induced and associated with clonal evolution). Advanced disease has varied clinical manifestations and may be associated with unusual and often life-threatening situations. We present here a rare case of continuous disease progression on tyrosine kinase inhibitor treatment with severe haemorrhagic manifestations in blast crisis, and posttransplant relapse. We also present a review of published literature.
- Klíčová slova
- ponatinib,
- MeSH
- chronická myeloidní leukemie * komplikace terapie MeSH
- dospělí MeSH
- hemoperitoneum MeSH
- lidé MeSH
- transplantace kostní dřeně MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
There are currently three thrombopoietin receptor agonists (TPO-RAs) approved in Europe for treating patients with immune thrombocytopenia (ITP): romiplostim (Nplate®), eltrombopag (Revolade®), and avatrombopag (Doptelet®). However, comparative clinical data between these TPO-RAs are limited. Therefore, the purpose of this study was to perform a literature review and seek expert opinion on the relevance and strength of the evidence concerning the use of TPO-RAs in adults with ITP. A systematic search was conducted in PubMed and Embase within the last 10 years and until June 20, 2022. A total of 478 unique articles were retrieved and reviewed for relevance. The expert consensus panel comprised ITP senior hematologists from eight countries across Central Europe. The modified Delphi method, consisting of two survey rounds, a teleconference and email correspondence, was used to reach consensus. Forty articles met the relevancy criteria and are included as supporting evidence, including five meta-analyses analyzing all three European-licensed TPO-RAs and comprising a total of 31 unique randomized controlled trials (RCTs). Consensus was reached on seven statements for the second-line use of TPO-RAs in the management of adult ITP patients. In addition, the expert panel discussed TPO-RA treatment in chronic ITP patients with mild/moderate COVID-19 and ITP patients in the first-line setting but failed to reach consensus. This work will facilitate informed decision-making for healthcare providers treating adult ITP patients with TPO-RAs. However, further studies are needed on the use of TPO-RAs in the first-line setting and specific patient populations.
- MeSH
- benzoáty terapeutické užití MeSH
- COVID-19 * MeSH
- dospělí MeSH
- hydraziny terapeutické užití MeSH
- idiopatická trombocytopenická purpura * farmakoterapie chemicky indukované MeSH
- konsensus MeSH
- lidé MeSH
- receptory Fc terapeutické užití MeSH
- receptory thrombopoetinu agonisté MeSH
- rekombinantní fúzní proteiny terapeutické užití MeSH
- thrombopoetin terapeutické užití MeSH
- trombocytopenie * chemicky indukované MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- systematický přehled MeSH
Východiská: Alogénna transplantácia kmeňových krvotvorných buniek (TKB) sa stala liečebnou modalitou pre mnohé malígne a nemalígne ochorenia. Počet dlhodobo prežívajúcich pacientov sa neustále zvyšuje. Transplantácia môže zapríčiniť poškodenia rôznych orgánov a tkanív – od minimálnych potenciálne progredujúcich subklinických zmien až po život ohrozujúce stavy. Cieľom tejto práce bolo vyhodnotiť prognostickú hodnotu vysokosenzitívneho kardiálneho troponínu T (hs-cTnT) a N-terminálneho fragmentu mozgového nátriuretického peptidu (NT-proBNP) v diagnostike kardiotoxicity, ako aj včasnej identifikácie vysokorizikových pacientov z hľadiska možného vzniku kardiálnej komplikácie po alogénnej TKB. Súbor pacientov a metódy: Súbor tvorilo 63 pacientov s hematologickými malignitami s mediánom veku 37 rokov v čase alogénnej TKB. Kardiálne biomarkery boli vyšetrované pred podaním prípravného režimu (PR) a deň +1, +14 a +30 po TKB. Systolická a diastolická funkcia bola vyhodnotená echokardiograficky pred podaním PR a 1 mesiac po TKB. Výsledky: Zmeny v koncentráciách NT-proBNP a hs-cTnT v priebehu 30 dní po TKB boli štatisticky významné (p < 0,001 vs. p = 0,02). U 7 pacientov (11,1 %) sa objavila kardiovaskulárna komplikácia, ktorá bola definovaná ako arytmia, perikardiálny výpotok s tamponádou srdca a srdcové zlyhanie. Multivariantnou analýzou sme zistili, že najsilnejším prognostickým faktorom kardiálnych komplikácií bolo súčasné pretrvávanie zvýšených hodnôt NT-proBNP a hs-cTnT s odstupom 14 dní od TKB (p < 0,0001). Pri súčasnej pozitivite obidvoch kardiálnych markerov v deň +14 po TKB bola zaznamenaná najlepšia hodnota oblasti pod krivkou (area under the curve – AUC) (0,95). Záver: Opakované meranie plazmatických koncentrácií NT-proBNP a hs-cTnT môže byť užitočným markerom pre včasnú detekciu poškodenia srdca u pacientov liečených alogénnou TKB a môže identifikovať pacientov s vysokým rizikom rozvoja kardiotoxicity. Súčasná pozitivita obidvoch kardiomarkerov bola silnejším prognostickým markerom ako len pozitivita jedného z nich.
Background: Allogeneic hematopoietic stem cell transplantation (HSCT) offers potentially curative therapy for numerous malignant and nonmalignant diseases. The number of survivors and length of follow-up after successful HSCT is continually increasing. HSCT can induce damage of various organs and tissues – from minimal potentially progressive subclinical changes to life-threatening conditions. The aim of this thesis was to assess the prognostic value of high sensitive cardiac troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) testing and early identification of patients at high risk of a cardiac event after allogeneic HSCT. Patients and methods: Sixty-three patients with the median age of 37 years at the time of allogeneic HSCT for hematologic diseases were studied. Cardiac biomarkers were serially measured before conditioning regimen and at days 1, 14 and 30 after HSCT. Cardiac systolic and diastolic functions were assessed before the conditioning regimen and 1 month after HSCT by echocardiography. Results: The differences in plasma NT-proBNP and hs-cTnT concentrations during the 30 days following HSCT were statistically significant (P < 0.001 vs. P = 0.02). Seven of 63 patients (11.1 %) developed a cardiac event defined as cardiovascular dysrhythmias, pericarditis with cardiac tamponade and heart failure. By multivariate analysis, the strongest prognostic factor of cardiac event was an increased level of hs-cTnT and NT-proBNP persisted for a period of 14 days after HSCT (P < 0.0001). The area under the curve from hs-cTnT testing plus NT-proBNP testing together (AUC = 0.95) was superior to each diagnostic modality alone. Conclusion: Measurements of plasma NT-proBNP and hs-cTnT concentrations might be a useful tool for identification of high-risk patients requiring further cardiological follow up. Measurement of hs-cTnT plus NT-proBNP together was superior to hs-cTnT and NT-proBNP measurements alone.
Background von Willebrand disease (VWD) is a genetic bleeding disorder caused by defects of von Willebrand factor (VWF), quantitative (type 1 and 3) or qualitative (type 2). The laboratory phenotyping is heterogenic making diagnosis difficult. Objectives Complete laboratory analysis of VWD as an expansion of the previously reported cross-sectional family-based VWD study in the Czech Republic (BRNO-VWD) and Slovakia (BRA-VWD) under the name "Heart of Europe," in order to improve the understanding of laboratory phenotype/genotype correlation. Patients and Methods In total, 227 suspected VWD patients were identified from historical records. Complete laboratory analysis was established using all available assays, including VWF multimers and genetic analysis. Results A total of 191 patients (from 119 families) were confirmed as having VWD. The majority was characterized as a type 1 VWD, followed by type 2. Multimeric patterns concordant with laboratory phenotypes were found in approximately 83% of all cases. A phenotype/genotype correlation was present in 84% (77% type 1, 99% type 2, and 61% type 3) of all patients. Another 45 candidate mutations (23 novel variations), not found in the initial study, could be identified (missense 75% and truncating 24%). An exon 1-3 gene deletion was identified in 14 patients where no mutation was found by direct DNA sequencing, increasing the linkage up to 92%, overall. Conclusion This study provides a cross-sectional overview of the VWD population in a part of Central Europe. It is an addition to the previously published BRNO-VWD study, and provides important data to the International Society of Thrombosis and Haemostasis/European Association for Haemophilia and Allied Disorders VWD mutation database with identification of novel causal mutations.
- Publikační typ
- časopisecké články MeSH
The next frontier in hemophilia A management has arrived. However, questions remain regarding the broader applicability of new and emerging hemophilia A therapies, such as the long-term safety and efficacy of non-factor therapies and optimal regimens for individual patients. With an ever-evolving clinical landscape, it is imperative for physicians to understand how available and future hemophilia A therapies could potentially be integrated into real-life clinical practice to improve patient outcomes. Against this background, nine hemophilia experts from Central European countries participated in a pre-advisory board meeting survey. The survey comprised 11 multiple-choice questions about current treatment practices and future factor and non-factor replacement therapies. The survey questions were developed to reflect current unmet needs in hemophilia management reflected in the literature. The experts also took part in a follow-up advisory board meeting to discuss the most important unmet needs for hemophilia management as well as the pre-meeting survey results. All experts highlighted the challenge of maintaining optimal trough levels with prophylaxis as their most pressing concern. Targeting trough levels of ≥30-50 IU/L or even higher to achieve less bleeding was highlighted as their preferred strategy. However, the experts had an equal opinion on how this could be achieved (i.e., more efficacious non-factor therapies or factor therapy offering broader personalization possibilities such as targeting trough levels to individual pharmacokinetic data). In summary, our study favors personalized prophylaxis to individual pharmacokinetic data rather than a "one-size-fits-all" approach to hemophilia A management to maintain optimal trough levels for individual patients.
- MeSH
- hemofilie A * farmakoterapie prevence a kontrola MeSH
- krvácení prevence a kontrola MeSH
- lidé MeSH
- znalecký posudek MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Evropa MeSH
Úvod: Liečba chronickej lymfocytovej leukémie (CLL) naďalej prechádza veľmi dynamickým vývojom. Chemoimunoterapia, ktorá bola hlavnou kostrou liečby, je do značnej miery nahradená cieľovými molekulami, ktoré sú účinnejšie a bezpečnejšie. Cieľ: Retrospektívna analýza vlastných dát na zhodnotenie výsledkov CLL pacientov liečených inovatívnou nechemoterapeutickou liečbou chemo-free. Materiál a metódy: V období od januára 2016 do septembra 2021 sme do štúdie zahrnuli 83 pacientov s chronickou lymfocytovou leukémiou, ktorí boli liečení na našom pracovisku. Celkovo 63 pacientov dostalo ibrutinib (15,9 % v prvej línii) a 20 pacientov dostalo venetoklax +/– rituximab (85 % v monoterapii a 5 % v prvej línii). Medián veku bol 64 rokov (rozsah 39–81 rokov). Každá skupina mala medián dvoch predchádzajúcich línií liečby (rozsah 1–6). Medián sledovania bol 31 mesiacov pri ibrutinibe a 23 mesiacov pri venetoklaxe. Výsledky: Väčšina pacientov odpovedala na liečbu s celkovou mierou odpovede (overall response rate – ORR) 92 % pri ibrutinibe a 90 % pri venetoklaxe. Miera kompletnej remisie bola vyššia pri venetoklaxe (relatívne riziko – RR = 2,02; 95% CI: 1,16–3,5; p = 0,012). Trojročné prežívanie bez progresie (progression-free survival – PFS) a celkové prežívanie (overall survival – OS) bolo 82 a 83 % pri ibrutinibe, 80 a 80 % pri venetoklaxe. Nežiaduce účinky boli väčšinou mierne alebo stredne závažné. Záver: V našej práci sme konštatovali, že nové molekuly ibrutinib a venetoklax poskytujú porovnateľné výsledky u pacientov s CLL liečených mimo klinického skúšania.
Introduction: Treatment of chronic lymphocytic leukaemia (CLL) continues to develop dramatically. Chemoimmunotherapy that historically represented the golden standard of treatment has been largely replaced by molecular-targeted therapies that are more effective and safer. Objective: A retrospective study to evaluate the efficacy and safety of innovative „chemo-free“ therapy (ibrutinib and venetoclax) in patients with CLL. Material and methods: from January 2016 to September 2021, 83 patients with chronic lymphocytic leukaemia treated in our institute were included in the study. A total of 63 patients received ibrutinib (15.9% in front-line setting) and 20 patients received venetoclax +/– rituximab (85% as monotherapy and 5% in front-line setting). The median age was 64 years (range 39–81 years). Each group had a median of two prior lines of therapy (range 1–6). The median follow-up was 31 months for ibrutinib and 23 months for venetoclax. Results: the majority of patients responded to treatment with an overall response rate (ORR) of 92% for ibrutinib and 90% for venetoclax. The rate of complete remission was higher with venetoclax (relative risk – RR = 2.02, 95% CI: 1.16–3.5; P = 0.012). The 3-year progression-free survival (PFS) and overall survival (OS) were 82% and 83% for ibrutinib, 80% and 80% for venetoclax respectively. The majority of side effects reported were relatively mild to moderate. Conclusion: In our study, we demonstrate that novel agents, ibrutinib and venetoclax provide comparable results in patients with CLL treated outside clinical trials.
- Klíčová slova
- Ibrutinib, venetoklax,
- MeSH
- adenin * analogy a deriváty aplikace a dávkování terapeutické užití MeSH
- chronická lymfatická leukemie * farmakoterapie imunologie MeSH
- cílená molekulární terapie MeSH
- dospělí MeSH
- Kaplanův-Meierův odhad MeSH
- lidé středního věku MeSH
- lidé MeSH
- nežádoucí účinky léčiv MeSH
- retrospektivní studie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- sulfonamidy * aplikace a dávkování terapeutické užití MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
Narastajúci objem dát a skúseností s použitím priamych orálnych antikoagulancií (DOAK) v primárnej aj sekundárnej prevencii venózneho tromboembolizmu u onkologických pacientov (CAVTE) viedol ku zmenám v početných medzinárodných odporúčaniach. Reflektujeme tieto zmeny s ohľadom na podmienky v SR. V primárnej prevencii CAVTE rozlišujeme onkologických pacientov na tých, ktorí podstupujú v súvislosti s ochorením chirurgický zákrok a na nechirurgických pacientov: hospitalizovaných a ambulantne liečených. Za základné liečivá v primárnej prevencii naďalej považujeme heparíny s nízkou molekulovou hmotnosťou (LMWH). V liečbe a sekundárnej prevencii CAVTE odporúčame uvažovať vždy aj o možnosti použiť DOAKy ako z hľadiska účinnosti rovnocennú alternatívu LMWH. LMWH je potrebné preferovať pred DOAKmi aj warfarinom u všetkých pacientov s klinicky nestabilnou situáciou s vysokým rizikom krvácania a vysokým rizikom interakcie so systémovou liečbou. Predovšetkým ide o pacientov s intraluminálnymi nádormi hornej časti gastrointestinálneho traktu a urogenitálnymi malignitami s vysokým rizikom krvácania. Pre nedostatočný objem dát sú LMWH stále preferované aj u pacientov s primárnymi nádormi a metastatickým postihnutím centrálnej nervovej sústavy a u hematoonkologických pacientov.
The increasing volume of the data and experience with direct oral anticoagulants (DOACS) in the primary and secondary prevention of venous thromboembolism in oncologic patients (CAVTE) has recently lead to changes in several international guidelines. We reflect these changes within the conditions in Slovak republic. In the primary prevention of CAVTE we recognise oncosurgical patients and nonsurgical patients: hospitalised and out patients. Low molecular weight heparins are still dominant in the primary prevention of CAVTE. Regarding the treatment and the secondary prevention of CAVTE, we recommend always to consider the possibility to use DOACs as they proved to be non inferior to LMWH. However, LMWH should be prefered over DOACs as well as over warfarin (VKA) in all patients who are in a clinically unstable condition with the high risk of bleeding and/or interaction with the systemic treatment. Primarily in the patients with intraluminal tumours of the upper part of the gastrointestinal tract and genitourinary tumours with the high risk of bleeding. As for the lack of data, LMWH are still preferd also in patients with primary tumours and metastatic disease of the central nervous system and in hemato oncology.
Východiská: Alogénna transplantácia kmeňových krvotvorných buniek (TKB) sa stala liečebnou modalitou pre mnohé malígne a nemalígne ochorenia. Počet dlhodobo prežívajúcich pacientov sa neustále zvyšuje. Transplantácia môže zapríčiniť poškodenia rôznych orgánov a tkanív – od minimálnych potenciálne progredujúcich subklinických zmien až po život ohrozujúce stavy. Cieľom tejto práce bolo zistiť prevalenciu metabolického syndrómu (MS) u pacientov po alogénnej TKB. Pacienti a metódy: Vyhodnotili sme 74 pacientov s mediánom veku 35 rokov v čase TKB a mediánom doby od transplantácie 5 rokov (2–23 rokov). MS sme vyhodnocovali podľa definície National Cholesterol Education Program – Adult Panel III (NCEP ATP III) a podľa definície International Diabetes Federation (IDF). Výsledky: Prevalencia MS po TKB podľa definície NCEP ATP III bola v našom súbore 40,5 % a podľa definície IDF 39,2 %, čo predstavuje 2,02 násobne vyšší výskyt ako v bežnej slovenskej populácii. MS sa častejšie vyskytoval u mužov a medzi najčastejšie komponenty patrila centrálna obezita, artériová hypertenzia a hypertriacylglycerolémia. Najnižšia prevalencia MS bola vo vekovej skupine 20–29 ročných, najvyššia v skupine 60–69 ročných pacientov. Desaťročná kumulatívna incidencia MS bola 32,5 %. Medzi rizikové faktory rozvoja MS patrilo celotelové ožiarenie, pozitívna rodinná anamnéza kardiovaskulárnych ochorení a vek > 40 rokov v čase TKB. U 7 pacientov (9,45 %) sa objavila kardiovaskulárna komplikácia. Medián všeobecného kardiovaskulárneho rizika pre mužov predstavoval hodnotu 13,3 % a pre ženy 6,68 %. Záver: Potvrdený zvýšený výskyt MS u pacientov prežívajúcich > 2 roky po TKB môže byť ďalším stimulom pre prospektívne štúdie a pre intervencie potrebné pre ich prevenciu.
Background: Allogeneic hematopoietic stem cell transplantation (HSCT) offers potentially curative therapy for numerous malignant and non-malignant diseases. The number of survivors and length of follow-up after successful HSCT is continually increasing. Hematopoietic stem cell transplantation can induce damage of various organs and tissues – from minimal potentially progressive subclinical changes to life-threatening conditions. The aim of this thesis was the evaluation of the prevalence of metabolic syndrome (MS) among survivors of allogeneic HSCT. Patients and methods: We analyzed 74 patients with a median age at transplant of 35 years, who had been followed for a median of 5 years (2–23 years) after allogeneic HSCT. MS was defined according to the National Cholesterol Education Program’s Adult Treatment Panel III (NCEP ATP III) criteria and by the International Diabetes Federation (IDF) definition. Results: The prevalence of MS among HSCT recipients was 40.5% applying the NCEP ATP III definition and 39.2% the IDF, a 2.02-fold increase compared to the general Slovak population. MS was more common in men. The most common MS features were abdominal obesity, hypertriglyceridemia and hypertension. The lowest prevalence of MS was in the age group of 20–29 years; and the highest prevalence in the age group of 60–69 years. The 10-year cumulative incidence of MS was 32.5%. The most significant risk factor for MS was total body irradiation, positive family history and age > 40 years at HSCT. Seven patients (9.45%) developed cardiovascular complications. The median 10-year general cardiovascular risk scores for males and females were found to be 13.3% and 6.68%, respectively. Conclusions: Detected increased prevalence of metabolic syndrome after allogeneic HSCT in patients surviving more than 2 years after this procedure may provide next stimulus to promote longer follow-up studies and to design of interventions to prevent late effects among survivors of serious hematologic diseases.
Background: florio HAEMO is a new hemophilia treatment monitoring application consisting of a patient smartphone application (app) and a web-based dashboard for healthcare professionals, providing several novel features, including activity tracking, wearable connectivity, kids and caregiver mode, and real-time pharmacokinetic factor level estimation. Objectives: To assess intuitiveness, ease-of-use, and patient preference of florio HAEMO in Central Europe using a cross-sectional survey. Methods: This survey was conducted in six Central European countries between 9 December 2020 and 24 May 2021. The online questionnaire included 17 questions about overall satisfaction, ease-of-use, intuitiveness, and patient preference. Adults or children with hemophilia on regular prophylaxis and using the florio HAEMO app for a minimum of 1 week were invited to complete the online questionnaire by their treating physician. Results: Sixty-six participants took part in the survey. The median duration for all respondents using the florio HAEMO app was 3 to 4 weeks. Overall, 89.4% of users reported being very satisfied or rather satisfied after using florio HAEMO. Of the 23 respondents who had switched from another hemophilia app, 87.0% indicated that they strongly preferred or preferred using florio HAEMO. Most florio HAEMO users reported that the app was very easy or rather easy to use (97.0%) and intuitive (94.0%). florio HAEMO had a positive impact on daily living, with 78.8% of users reporting that the app was very important or rather important to them. Conclusions: This survey suggests that florio HAEMO is an easy-to-use and intuitive app to assist self-management of home prophylaxis.
- Publikační typ
- časopisecké články MeSH
