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  • Author: Lidia Gil x
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Chimeric antigen receptor T-cell (CAR-T) therapy is an effective new treatment for hematologic malignancies. Two anti-CD19 CAR-T products, namely axicabtagene ciloleucel and tisagenlecleucel, have been approved for the management of relapsed/refractory large B-cell lymphoma after two lines of systemic therapy. Additionally, tisagenlecleucel is indicated for refractory acute lymphoblastic leukemia in pediatric patients and young adults up to 25 years of age. CAR-T cells are undoubtedly a major breakthrough therapy in hematooncology resulting in up to 90% response rate with durable remissions in population with refractory high-risk disease. However, there are serious side effects resulting from CAR-T therapy, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Manifestations of CRS mostly include fever, hypotension, hypoxia, and end organ dysfunction. Neurologic toxicities are diverse and include encephalopathy, cognitive defects, dysphasia, seizures, and cerebral edema. Since the symptoms are potentially severe, practitioners need to familiarize themselves with the unique toxicities associated with these therapies. In this article, we present a practical guideline for diagnosis, grading and management of CRS and CAR-T neurotoxicity. In addition, infectious complications and late toxicities including prolonged cytopenias and hypogammaglobulinemia are discussed.


Cardiac amyloidosis is a rare and often-misdiagnosed disorder. Among other forms of deposits affecting the heart, immunoglobulin-derived light-chain amyloidosis (AL amyloidosis) is the most serious form of the disease. Delay in diagnosis and treatment may have a major impact on the prognosis and outcomes of patients. This review focuses on the presentation of the disorder and current novel approaches to the diagnosis of cardiac involvement in AL amyloidosis.


The BIRC6 gene encodes the Bruce (Apollon) protein. This belongs to the III class of Inhibitors of the Apoptosis Protein (IAP) and demonstrates anti-apoptotic activity (binding, inhibiting and degrading the caspases). Moreover, the Bruce protein shows multilevel activities and additional functions. The Bruce protein is involved in the maintenance of cell viability, and it is also suggested that it plays an important role in cell proliferation and diversification. Many researchers have noticed elevated BIRC6 gene expression in cell lines of brain cancer and ovarian carcinoma, leukemia, breast cancer and even in colorectal cancer tissues. Resistance to chemotherapy-inducted apoptosis in cancers characterized by BIRC6 gene over-expression was also reported. The aim of the study was to assess the BIRC6 gene expression in peripheral blood lymphocytes of patients diagnosed with chronic lymphocytic leukemia.


Leki biopodobne odgrywają coraz większą rolę w terapii wielu chorób wraz z wygaśnięciem ochrony patentowej dla kolejnych leków biologicznych. Celem niniejszego opracowania jest przybliżenie terminologii i zasad wprowadzania na rynek leków biopodobnych, zagadnień dotyczących ich etykietowania, ekstrapolacji, wymienialności i automatycznej substytucji. Opracowanie to przedstawia stanowisko Polskiego Towarzystwa Hematologów i Transfuzjologów dotyczące leków biopodobnych, oparte na wytycznych EMA (European Medicine Agency) i stanowisku ESMO (European Society of Medical Oncology).


Invasive fungal disease (IFD) is one of the most serious complications of therapy in patients with immune suppression. It particularly concerns patients treated for malignant hematological diseases, immune deficiencies, or undergoing hematopoietic cell transplantation (HCT). Development of IFD can abrogate the effect of previous therapy and contributes to dismal outcome of the underlying disease. The Working Group consisting of members of the Polish Society of Hematology and Blood Transfusion, the Polish Society of Pediatric Oncology and Hematology, and the Polish Adult Leukemia Study Group has prepared recommendations for the diagnostic and therapeutic management of IFD in adults and children. This paper presents the current recommendations for patients in immune suppression treated in Polish pediatric and adult hematology and HCT centers, based on the guidelines of the European Conference on Infections in Leukaemia (ECIL) 2015–2019. Levels of diagnosis of IFD (possible, probable, and proven) and antifungal management (prophylaxis, as well as empirical and targeted therapies) are declared according to updated international criteria of the European Organization for Research and Treatment of Cancer and the Mycoses Study Group (EORTC/MSG) 2019. Patients with primary diagnosis of acute lymphoblastic leukemia, acute myeloblastic leukemia, severe aplastic anemia, chronic granulomatous disease, and severe combined immunodeficiency, as well as patients after allogeneic HCT, are included in the high-risk groups for development of IFD. For these patients, antifungal prophylaxis based on azoles or micafungin is recommended. In empirical therapy, caspofungin or liposomal/lipid formulas of amphotericin B are recommended. The Working Group has discouraged the use of itraconazole in capsules and amphotericin deoxycholate. Detailed guidelines for first- and second-line targeted therapies for invasive candidiasis, aspergillosis, mucormycosis, fusariosis, and scedosporiosis, as well as the principles of the recommended dosing of antifungals, are presented in this paper.


Reaktywacja zakażenia HBV jest istotnym problemem u chorych poddawanych terapiom, które poprzez działanie immunomodulujące wpływają na upośledzenie odporności przeciwwirusowej, takim jak: leczenie biologiczne (np. przeciwciała monoklonalne powodujące deplecję limfocytów CD20, przeciwciała anty-TNF), chemioterapia, leczenie immunosupresyjne (np. kortykosteroidy, cyklosporyna, azatiopryna). Ryzyko reaktywacji wiąże się również z nowymi terapiami stosowanymi w leczeniu nowotworów hematologicznych, takimi jaki inhibitory kinaz tyrozynowych, inhibitory proteasomu czy przeciwciało anty-CD38, daratumumab. Populacją szczególnie zagrożoną są chorzy poddawani transplantacji komórek krwiotwórczych, w szczególności chorzy po transplantacji allogenicznej, u których prowadzone jest leczenie immunosupresyjne. W pracy przedstawiono epidemiologię, czynniki ryzyka reaktywacji oraz aktualne zasady postępowania dotyczące profilaktyki reaktywacji zakażenia HBV.


The objective of this paper is to present the process of the national and international accreditation leading to the establishment of the first certified chimeric antigen receptor T (CAR-T) Cell Unit in Poland on the basis of the Department of Hematology and Bone Marrow Transplantation in Poznan University of Medical Sciences and first successful CAR-T therapy in Poland. During 12 months from the initial decision to establish the CAR-T Cell Unit to the application of CAR-T cell treatment in the first patient, the center had to undergo the multidisciplinary external and internal training, as well as the adaptation of multiple procedures within the Transplant Unit and Stem Cell Bank. In order to get accreditation for the implementation of CAR-T cell therapy, an initial training of the team involved in handling cellular products and patient care was organized and updated as a continuous process. The Department fulfilled the site-selection international criteria. The first patient diagnosed for refractory/relapsed DLBCL was qualified, and finally CAR-T cells were administered with successful clinical outcome.


Introduction. Recent research shows that programmed cell death has great importance in the pathomechanism of atherosclerosis. The BIRC5 and BIRC6 genes belong to Class III IAPs with the anti-apoptotic effect. The proteins display multidirectional action. According to the available literature, in addition to the effect of apoptosis inhibition they also display other properties. It is suggested that they play an important role in the processes of proliferation and cellular differentiation. Aim. The aim of the study was to assess the expression of the BIRC5 and BIRC6 genes in normal peripheral blood lymphocytes and in peripheral blood lymphocytes of patients diagnosed with atherosclerosis. Material and methods. The analysis was carried out on RNA samples obtained from peripheral blood lymphocytes of 21 patients with diagnosed atherosclerosis. The specific fragment of the analysed gene was obtained through amplification with the use of cDNA synthesised in the reaction of reverse transcription. The test of expression was conducted with the use of the Real-Time PCR method. In the studied cases, the level of expression of the analysed gene was compared to the level of expression of the reference gene, B2M. Results. The study showed that mRNA of the BIRC5 and BIRC6 genes is present in the cells of patients with atherosclerosis, as well as in the cells of healthy individuals. The cells taken from the patients with atherosclerosis were mainly characterized by an increased gene expression in comparison to the normal cells. Conclusion. Increased BIRC6 and BIRC5 gene expression in the cells of the patients with atherosclerosis can suggest an increased amount of the inhibitor protein BRUCE and survivin, and also decreased sensitivity of cells to apoptosis. In the case of the patients who had significantly higher expression of the BIRC6 gene in lymphocytes compared to the norm, hypertension and diabetes mellitus were more common


Zakażenia należą do najczęstszych przyczyn chorobowości i śmiertelności chorych na nowotwory hematologiczne, a stosowanie szczepień ochronnych może w istotnym stopniu wpłynąć na zmniejszenie częstości ich występowania. W pracy przedstawiono przegląd danych dotyczących ryzyka zakażeń oraz skuteczności immunizacji czynnej u chorych na nowotwory hematologiczne i u pacjentów z anatomiczną lub czynnościową asplenią. Ponadto zawarto rekomendacje dla populacji polskich pacjentów opracowane przez Sekcję Zakażeń Polskiej Grupy ds. Leczenia Białaczek u Dorosłych (PALG) oraz Polskie Towarzystwo Hematologów i Transfuzjologów. Uwzględniono zarówno zalecenia ogólne dotyczące chorych na nowotwory, jak i szczegółowe odnoszące się do określonych nowotworów hematologicznych. Przedstawiono również propozycje poprawy organizacji szczepień u chorych na nowotwory hematologiczne w Polsce.



In patients with acute leukemia, lymphoma and chronic malignancies, donor and/or recipient Epstein-Barr virus (EBV) seropositive status increases the risk of development of chronic graft-versus-host disease (cGVHD) after allo-hematopoietic cell transplantation (allo-HCT), while it has no influence on other transplant outcomes. No data are available on the impact of EBV serostatus on transplant outcomes in patients with nonmalignant hematological disorders.


We analyzed the influence of the recipient's (R) and donor's (D) EBV serostatus on transplant outcomes (overall survival (OS); relapse-free survival (RFS); relapse incidence (RI); nonrelapse mortality (NRM); acute graft-versus-host disease (aGVHD); cGVHD) in patients with nonmalignant hematological disorders undergoing allo-HCT.

Patients and Methods

A total of 2,355 allo-HCTs performed between 1997 and 2016 for acquired bone marrow failure or hemoglobinopathies were included in this retrospective Registry megafile Infectious Diseases Working Party of the European Society of Blood and Marrow Transplantation (IDWP-EBMT) study.


Demographics: The median age of recipient was 17.7 years (range: 0–77), and 50.8% were children. 79.0% of recipients and 75.4% of donors were EBV-seropositive. 67.8% had HCT from a matched family donor, 4.6% from a mismatched family donor, and 27.6% from an unrelated donor (UD). T-cell depletion was performed in vivo and ex vivo in 82.2% and 6.6% of patients, respectively. Conditioning regimen was myeloablative in 63.7% and reduced intensity conditioning (RIC) in 36.3% of patients. The median follow-up was 4.7 years. Transplant outcomes: EBV-seropositive recipients in comparison with EBV-seronegative recipients had lower OS (85.4% vs. 88.4%, p = 0.035) and higher NRM (10.0% vs. 6.4%, p = 0.018). No other significant differences were found for: RI, RFS, and aGVHD or cGVHD with respect to EBV pretransplant serostatus donor and/or recipient. Multivariate analysis: A trend toward higher risk of development of cGVHD (HR = 1.31; p = 0.081) and better survival (HR = 0.78; p = 0.087) in allo-HCT from EBV-seropositive donors was found. Allo-HCT in EBV-seropositive recipients had a trend toward lower risk of development of cGVHD (HR = 0.75; p = 0.065). When four subgroups (R−/D−, R−/D+, R+/D−, R+/D+ EBV serology) were analyzed, the EBV serostatus had no significant impact on OS, RFS, RI, NRM and development of aGVHD or cGVHD.


Allo-HCT from EBV-seropositive versus EBV-seronegative donors are at 31% higher risk of cGVHD in patients with nonmalignant hematological disorders undergoing allo-HCT; however this difference is nonsignificant in multivariate analysis.