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Innowacyjna terapia CAR-T w leczeniu nowotworów hematologicznych — wybrane aspekty genetyczne i immunologiczne
Hematologia Pub Date : 2020-12-27 DOI: 10.5603/HEM.A2020.0025
K. Karwicka, J. Wawer, Olga Czabak, J. Kocki, Marek Hus
{"title":"Innowacyjna terapia CAR-T w leczeniu nowotworów hematologicznych — wybrane aspekty genetyczne i immunologiczne","authors":"K. Karwicka, J. Wawer, Olga Czabak, J. Kocki, Marek Hus","doi":"10.5603/HEM.A2020.0025","DOIUrl":"https://doi.org/10.5603/HEM.A2020.0025","url":null,"abstract":"Genetic modification of T lymphocytes which can produce the expression of chimeric antigen receptor (CAR) has been used a novel option for the treatment of haematological malignancies. The results seem to be promising. Reprogrammed T cells recognize specific antigens on the surface of target cells, which in turn triggers their activation independently of MHC. Appropriate antigen selectivity and intracellular signalling facilitates killing cancer cells. The use of anti-CD19 CAR-T lymphocytes in the treatment of DLBCL and ALL has radically changed the way lymphoid neoplasms are treated, especially in patients who experience relapses or resist standard therapies. The genetic transduction involves not only CAR fusion protein modified by a retrovirus or lentivirus, but also costimulatory domains, suicide genes, and transgenes to produce additional effector molecules and CAR bispecific checkpoint inhibitors. Modern genetic engineering technologies such as TALEN or CRISPR/Cas9 are used to edit genes. Their goal is to improve the response rate and extend remission duration time, target new disease entities, reduce toxicity, and possibly create ‘universal CAR-T cells’. Potential mechanisms of CAR-T lymphocyte failure include tumor escaping from immune surveillance (e.g., by loss of CD19 expression), immunosuppressive microenvironment, depletion of CAR-T lymphocytes, or their decreased activity. This review also discusses potential toxicity and possible ways to prevent or treat dangerous or life-threatening adverse effects of the therapy.","PeriodicalId":38988,"journal":{"name":"Hematologia","volume":"56 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81247110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Powikłania endokrynologiczne i metaboliczne terapii chorób rozrostowych układu krwiotwórczego
Hematologia Pub Date : 2020-12-27 DOI: 10.5603/HEM.A2020.0024
Michał Litwińczuk, Joanna Szydełko, M. Szydełko, Monika Podhorecka, Agnieszka Szymczyk
{"title":"Powikłania endokrynologiczne i metaboliczne terapii chorób rozrostowych układu krwiotwórczego","authors":"Michał Litwińczuk, Joanna Szydełko, M. Szydełko, Monika Podhorecka, Agnieszka Szymczyk","doi":"10.5603/HEM.A2020.0024","DOIUrl":"https://doi.org/10.5603/HEM.A2020.0024","url":null,"abstract":"Despite the significant progress in the treatment of haematological malignancies and the improvement of treatment efficacy, it is still associated with numerous side effects. Among them, endocrinological and diabetic complications of immunotherapy are of particular importance, and they belong to the most frequently observed, mainly due to the interference of the treatment with functioning of the immune system. As a result, it can lead to the induction of autoimmune processes in many systems, including endocrine glands. The effectiveness of some therapies may also be determined by the occurrence of side effects in the form of autoimmune diseases. Increasing use of tyrosine kinase inhibitors, immune checkpoint inhibitors, as well as glucocorticosteroids exerting immunosuppressive effect, which are applied, leads to the development of various pathologies of the endocrine system. The most common complications developing on the background of autoimmune inflammation are disturbances in the function of thyroid gland, pituitary gland in its anterior lobe, and very rarely in the posterior lobe in the form of diabetes insipidus. The above-mentioned disorders may occur in patients of all ages, regardless of gender. Some dysfunctions are subclinical and are found incidentally during routine check-up, both in the course of the treatment process or after its completion. Taking into account the possibility of serious consequences of the therapy, it is now recommended to periodically control the patients.","PeriodicalId":38988,"journal":{"name":"Hematologia","volume":"62 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87059907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Od Redaktora
Hematologia Pub Date : 2020-12-27 DOI: 10.5603/hem.2020.0027
I. Hus
{"title":"Od Redaktora","authors":"I. Hus","doi":"10.5603/hem.2020.0027","DOIUrl":"https://doi.org/10.5603/hem.2020.0027","url":null,"abstract":"","PeriodicalId":38988,"journal":{"name":"Hematologia","volume":"62 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90258639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Pierwotne chłoniaki nadnerczy jako interdyscyplinarny problem endokrynologiczny i hematologiczny — praktyczne wskazówki w zakresie diagnostyki i leczenia
Hematologia Pub Date : 2020-12-27 DOI: 10.5603/HEM.A2020.0023
Joanna Szydełko, Michał Litwińczuk, M. Szydełko, Monika Podhorecka, Agnieszka Szymczyk
{"title":"Pierwotne chłoniaki nadnerczy jako interdyscyplinarny problem endokrynologiczny i hematologiczny — praktyczne wskazówki w zakresie diagnostyki i leczenia","authors":"Joanna Szydełko, Michał Litwińczuk, M. Szydełko, Monika Podhorecka, Agnieszka Szymczyk","doi":"10.5603/HEM.A2020.0023","DOIUrl":"https://doi.org/10.5603/HEM.A2020.0023","url":null,"abstract":"Primary adrenal lymphomas (PAL) are rare neoplasms that should be considered in the differential diagnosis of adrenal insufficiency and incidentally detected focal lesions within the adrenal glands, especially those located bilaterally. PAL are tumors characterized by a rapid growth, an aggressive course and a poor prognosis. The disease usually develops in the elderly, most often in the 6.–7. decade of life, 2–7 times more often in men than in women. The etiopathogenesis of PAL is complex, multifactorial and still not fully understood.. The most commonly reported symptoms include fever of unknown origin, abdominal pain, fatigue, and weight loss. In the case of lesions localized on both sides, symptoms of adrenal insufficiency are relatively common. PAL may also be clinically silent and be detected as incidentalomas. The examination of choice in PAL diagnostics is computed tomography (CT) of the abdominal cavity aimed at the adrenal glands and combined with hormonal assessment. The gold standard in the diagnosis of PAL is percutaneous fine-needle aspiration biopsy under ultrasound or CT guidance, which allows for the final diagnosis. Histopathologically, the vast majority of cases are diffuse large B-cell lymphoma. It has been suggested to combine various methods of treatment, including immunochemotherapy/chemotherapy, surgery with subsequent immunochemotherapy/chemotherapy and/or radiotherapy. The purpose of the following systematic review was to perform an interdisciplinary analysis of the clinical picture, pathogenesis, diagnostic methods and current therapeutic strategies, taking into account the prognosis for individual PAL subtypes.","PeriodicalId":38988,"journal":{"name":"Hematologia","volume":"21 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89878189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Bezpieczeństwo i skuteczność protokołu wenetoklaks–rytuksymab u chorej na przewlekłą białaczkę limfocytową leczonej uprzednio inhibitorem BTK
Hematologia Pub Date : 2020-12-27 DOI: 10.5603/HEM.2020.0022
Joanna Drozd-Sokołowska, Grzegorz W. Basak
{"title":"Bezpieczeństwo i skuteczność protokołu wenetoklaks–rytuksymab u chorej na przewlekłą białaczkę limfocytową leczonej uprzednio inhibitorem BTK","authors":"Joanna Drozd-Sokołowska, Grzegorz W. Basak","doi":"10.5603/HEM.2020.0022","DOIUrl":"https://doi.org/10.5603/HEM.2020.0022","url":null,"abstract":"Wenetoklaks, bedący inhibitorem BCL2, stosowany w skojarzeniu z rytuksymabem jest skuteczny w leczeniu przewleklej bialaczki limfocytowej (CLL), zarowno z del(17p) i/lub mutacją TP53 , jak i bez tych nieprawidlowości. W artykule zaprezentowano przypadek 50-letniej chorej, u ktorej w wieku 34 lat rozpoznano CLL i ktorą z tego powodu leczono wieloma liniami chemioimmunoterapii, w tym zawierającymi fludarabine. W ostatnim okresie chora otrzymywala inhibitor kinazy tyrozynowej Brutona — ibrutynib. Po 52 miesiącach odpowiedzi na ibrutynib u chorej doszlo do progresji choroby z obecnością objawow ogolnych i z ewolucją klonalną pod postacią nowej del(17p). Chorą zakwalifikowano do leczenia wenetoklaksem, stosowanym przez 2 lata od 1. dnia 1. cyklu w dawce 400 mg/dobe, po wcześniejszym 5-tygodniowym stopniowym zwiekszaniu dawki, w skojarzeniu z rytuksymabem, stosowanym przez pierwsze 6 miesiecy leczenia. \u0000Pierwsze miareczkowanie wenetoklaksu przerwano przy dawce 50 mg/dobe ze wzgledu na gorączke i neutropenie 3. stopnia. Po wykluczeniu transformacji Richtera i potencjalnych zakazen w trakcie kolejnego miareczkowania wenetoklaksu stosowano krotkodzialający czynnik wzrostu granulocytow (G-CSF) i leki przeciwgorączkowe. Bez powiklan klinicznych osiągnieto dawke docelową i rozpoczeto leczenie rytuksymabem. W wyniku zastosowanego leczenia uzyskano ustąpienie limfadenopatii i objawow ogolnych oraz istotną poprawe parametrow morfologii krwi obwodowej. Chora kontynuuje leczenie. \u0000Podsumowując, zastosowanie protokolu wenetoklaks–rytuksymab jest skuteczne, rowniez u chorych po wielu liniach leczenia i u chorych z del(17p). Odpowiedź na leczenie jest szybka, niemniej w pierwszym okresie leczenia mogą wystepowac dzialania niepoządane, takie jak neutropenia. Zasadne moze byc rownoczesne stosowanie G-CSF w celu umozliwienia szybkiego osiągniecia dawki docelowej wenetoklaksu.","PeriodicalId":38988,"journal":{"name":"Hematologia","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84089926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Leczenie farmakologiczne pierwotnej małopłytkowości immunologicznej u dorosłych
Hematologia Pub Date : 2020-10-30 DOI: 10.5603/hem.2020.0009
K. Chojnowski
{"title":"Leczenie farmakologiczne pierwotnej małopłytkowości immunologicznej u dorosłych","authors":"K. Chojnowski","doi":"10.5603/hem.2020.0009","DOIUrl":"https://doi.org/10.5603/hem.2020.0009","url":null,"abstract":"","PeriodicalId":38988,"journal":{"name":"Hematologia","volume":"44 1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79327357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 3
Przegląd informacji na temat COVID-19 oraz wywołującego ją SARS-CoV-2
Hematologia Pub Date : 2020-10-30 DOI: 10.5603/HEM.2020.0011
Justyna Błach, J. Roliński
{"title":"Przegląd informacji na temat COVID-19 oraz wywołującego ją SARS-CoV-2","authors":"Justyna Błach, J. Roliński","doi":"10.5603/HEM.2020.0011","DOIUrl":"https://doi.org/10.5603/HEM.2020.0011","url":null,"abstract":"In December 2019, in Wuhan (Hubei province) in China, an unknown cause of pneumonia was diagnosed In January 2020, a new coronavirus was identified, which was called SARS-CoV-2 (severe acute respiratory syndrome-related coronavirus 2) The World Health Organization has declared the disease caused by SARS-CoV-2 as COVID-19 (coronavirus disease 2019) Currently, COVID-19 disease has spread widely throughout the world, the virus has already been detected in 185 countries (as of 29 04 2020) In this review, we summarized the clinical features, diagnosis and immunopathology of the SARS-CoV-2 We emphasize the need for further research into therapies used to treat COVID-19 Only a comprehensive understanding of these issues will help control the disease Copyright © 2020 Via Medica","PeriodicalId":38988,"journal":{"name":"Hematologia","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72887803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Od Redakcji
Hematologia Pub Date : 2020-10-30 DOI: 10.5603/hem.2020.0015
I. Hus
{"title":"Od Redakcji","authors":"I. Hus","doi":"10.5603/hem.2020.0015","DOIUrl":"https://doi.org/10.5603/hem.2020.0015","url":null,"abstract":"","PeriodicalId":38988,"journal":{"name":"Hematologia","volume":"53 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86068488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Nocna napadowa hemoglobinuria — aktualny stan wiedzy, diagnostyka, dostępne terapie i perspektywy na przyszłość
Hematologia Pub Date : 2020-06-30 DOI: 10.5603/hem.2020.0004
Agnieszka Piekarska, K. Lewandowski
{"title":"Nocna napadowa hemoglobinuria — aktualny stan wiedzy, diagnostyka, dostępne terapie i perspektywy na przyszłość","authors":"Agnieszka Piekarska, K. Lewandowski","doi":"10.5603/hem.2020.0004","DOIUrl":"https://doi.org/10.5603/hem.2020.0004","url":null,"abstract":"Nocna napadowa hemoglobinuria (PNH) jest sierocą chorobą o charakterze klonalnym, wywolaną nabytą mutacją krwiotworczej komorki macierzystej. Mutacja w genie PIGA skutkuje niedoborem lub brakiem na komorkach potomnych bialek blonowych związanych z kotwicą glikozylofosfatydyloinozytolu, w tym inhibitorow dopelniacza CD55 i CD59. Brak kontroli nad aktywacją dopelniacza prowadzi do ciąglej hemolizy, co w glownej mierze odpowiada za powiklania zakrzepowo-zatorowe bedące zasadniczą przyczyną chorobowości i śmiertelności w PNH. Od roku 2019 dostepna jest w Polsce terapia ekulizumabem, przeciwcialem monoklonalnym zarejestrowanym do leczenia pacjentow z hemolizą i wysoką aktywnością choroby lub powiklaniami zakrzepowymi. Program lekowy poprawil perspektywe pacjentow i zmienil podejście do kwalifikacji do transplantacji alogenicznych komorek krwiotworczych w naszym kraju. Dodatkowo, w 2019 roku zarejestrowano w Europie rawulizumab, skutecznie kontrolujący hemolize przy podazy co 8 tygodni. Trwają rowniez badania kliniczne nad nowymi lekami. W opiece nad chorymi leczonymi inhibitorami dopelniacza nie mozna zapominac o ryzyku infekcji bakteriami otoczkowymi. W opracowaniu przedstawiono patomechanizm kluczowych zaburzen oraz omowiono wspolczesne zalecenia diagnostyczne i opcje terapeutyczne w PNH.","PeriodicalId":38988,"journal":{"name":"Hematologia","volume":"33 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78720642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Czy zastosowanie autologicznych preparatów krwiopochodnych będzie złotym standardem w różnych specjalizacjach medycyny XXI wieku?
Hematologia Pub Date : 2020-06-30 DOI: 10.5603/hem.2020.0002
J. Nowak, Marcin Adamiec, B. Iwańczyk, Maciej R. Czerniuk
{"title":"Czy zastosowanie autologicznych preparatów krwiopochodnych będzie złotym standardem w różnych specjalizacjach medycyny XXI wieku?","authors":"J. Nowak, Marcin Adamiec, B. Iwańczyk, Maciej R. Czerniuk","doi":"10.5603/hem.2020.0002","DOIUrl":"https://doi.org/10.5603/hem.2020.0002","url":null,"abstract":"Due to the positive effect of the use of platelet concentrates, blood derivatives are currently used in many medical specialties. Platelet rich plasma was the first generation of this autogenic material and has been most commonly used so far. The exceptions were the fields of dentistry – oral and maxillofacial surgery, periodontics and implant surgery, where platelet rich fibrin (Platelet Rich Fibrin, PRF) was more widely. However, a changing trend is also visible in other fields of medicine, where PRF is becoming more important. The reason for the use of platelet concentrates and the ability to match their type to a specific surgical procedure is extremely important because of the different physico-chemical and biological properties. \u0000 This article will introduce the use of autologous blood derivatives. The multitude of potential applications in medicine proves versatility, minimal risk of complications associated with the use of platelet concentrates, and above all - improvement of all parameters related to healing, tissue regeneration or prevention of complications after surgery. Undoubtedly, the scope of indications for the use of these preparations will increase, and the protocols for their preparation will be improved.","PeriodicalId":38988,"journal":{"name":"Hematologia","volume":"81 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90772524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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