Helicobacter pylori

Nowadays, it is believed that the main role in the development of gastric mucosa-associated lymphoid tissue (MALT) lymphoma plays Helicobacter pylori infection. This world-wide distributed bacteria is in charge of most cases of not only upper gastrointestinal tract disorders but also some of extragastric problems. Constant stimulation of the immune system causes a B-lymphocytes proliferation, which is considered to be responsible for the neoplastic transformation. On the other hand, there are 10%–20% of patients who do not respond to Helicobacter pylori eradication treatment. This group has often a chromosome translocation, which suggests that there is another unknown, so far, pathogenetic mechanism of MALT lymphoma. Majority of genetic abnormalities are connected with nuclear factor-κB (NF-κB) pathway, which activates the uncontrolled proliferation of neoplastic cells. Translocations already described in studies are t(11;18)(q21;q21), which is the most common, t(14;18)(q32;q21), t(14;18)(q32;q21), and t(3;14)(p14.1;q32). This non-Hodgkin's lymphoma is an indolent type originated outside lymph nodes. In more than 50% of cases, it occurs in the stomach. Occasionally, it can be found in salivary and thyroid gland, lung, breast, bladder, skin, or any other place in the human body. This paper is a review of the current knowledge on etiology, pathogenesis, treatment, and follow-up of gastric MALT lymphoma

Leczenie podtrzymujące u chorych na chłoniaka grudkowego

Follicular lymphoma (FL) is a relatively frequent malignant disease, comprising approximately 20% of lymphoid malignancies. Clinically it is defined as an indolent disease. Despite the recent progress in treatment of hematological tumors, FL still remains an incurable disease. In patients with progressive disease, a standard of first line treatment are COP (cyclophosphamide, vincristine, prednizon) or CHOP (cyclophosphamide, doksorubicine, vincristine, prednizon) regimens, administrated in combination with anti-CD20 antigen antibody, rituximab (RIT). Most recently, the role of RIT maintenance in prolongation of disease progression free survival and, potentially, overall survival of FL patients has been underlined. Onkol. Prak. Klin. 2011; 7, 2: 84–88Chłoniak grudkowy (FL) stanowi około 20% wszystkich nowotworów układu chłonnego. Należy on do grupy tak zwanych przewlekłych chłoniaków złośliwych nieziarniczych. Pomimo postępu w leczeniu chorób nowotworowych krwi, który osiągnięto w ostatnich latach, FL wciąż pozostaje chorobą nieuleczalną. U pacjentów z progresywną postacią FL standardem leczenia pierwszoliniowego jest chemioterapia według schematu COP (cyklofofamid, winkrystyna, prednizon) lub CHOP (cyklofofamid, doksorubicyna, winkrystyna, prednizon), skojarzona z przeciwciałem monoklonalnym anty-CD20, rituksymabem (RIT). W ostatnim czasie wskazuje się na rolę leczenia podtrzymującego RIT w przedłużeniu czasu do progresji choroby, a być może także całkowitego przeżycia chorych na FL. Onkol. Prak. Klin. 2011; 7, 2: 84–8

Cytometria przepływowa w diagnostyce różnicowej choroby Hashimoto i chłoniaka MALT tarczycy

 Introduction: A combination of traditional cytology methods with fluorescence activated cell sorting (FACS) analysis of fine-needle aspiration biopsy (FNAB) material is considered a powerful diagnostic tool in the differential diagnosis of thyroid lesions suspected of mucosa-associated lymphoid tissue lymphoma (MALT-L). The aim of this study was to demonstrate the FACS-based diagnostic process of thyroid lesions in a clinical situation where ultrasound and cytological examinations did not allow differentiation between Hashimoto’s thyroiditis (HT) and MALT-L. Material and methods: The patients analysed in this study presented significantly different clinical courses of thyroid disease: quickly enlarging painless tumour of the thyroid right lobe in the first case, and chronic HT with palpable tumour in the thyroid isthmus in the second patient. Due to the suspicion of MALT-L resulting from indeterminate ultrasound and FNAB-cytology results, FNAB material was obtained from all the previously examined thyroid lesions and directly subjected to FACS assessment, encompassing κ/λ light chain restriction analysis, as well as measurements of B and T cell surface antigens. Results: The FACS analysis of FNAB material obtained from our patients did not show any definite signs of light chain restriction. Although one of the samples showed a borderline value of κ/λ ratio (κ/λ = 0.31), further immunophenotyping confirmed clonal expansion in none of the examined thyroid regions. Histopathological findings documented the diagnosis of HT in both clinical cases. Conclusion: We believe that FACS represents a useful and reliable complementary diagnostic measure in FNAB-based differential diagnosis of lymphoproliferative thyroid disorders. Wstęp: Skojarzenie oceny cytologicznej oraz cytometrii przepływowej (FACS, fluorescence activated cell sorting) materiału uzyskanego podczas biopsji aspiracyjnej cienkoigłowej (BAC) jest uważane za niezwykle skuteczną metodę w diagnostyce różnicowej zmian tarczycy podejrzanych o obecność pozawęzłowego chłoniaka strefy brzeżnej systemu MALT (MALT-L). Celem pracy było zaprezentowanie opartego na FACS procesu diagnostycznego zmian ogniskowych tarczycy u chorych, u których badanie ultrasonograficzne i cytologiczne nie umożliwiło zróżnicowania przewlekłego zapalenia tarczycy (HT, Hashimoto's thyroiditis) od MALT-L. Materiał i metody: Chorzy opisani w pracy charakteryzowali się całkowicie odmiennym przebiegiem klinicznym choroby tarczycy — ujawniającej się w pierwszym przypadku jako szybko powiększający się guz płata prawego, w drugim jako zmiana ogniskowa w cieśni u chorej z przewlekłym wywiadem HT. Ze względu na podejrzenie MALT-L postawione na podstawie badania cytologicznego oraz podejrzany wzorzec ultrasonograficzny, przeprowadzono ponownie BAC wszystkich wcześniej ocenianych zmian tarczycy, a uzyskany materiał poddano bezpośrednio ocenie za pomocą FACS, obejmującej analizę restrykcji łańcuchów lekkich immunoglobulin κ/λ oraz antygenów powierzchniowych limfocytów T i B. Wyniki: Analiza FACS materiału uzyskanego za pomocą BAC nie ujawniła definitywnych cech restrykcji łańcuchów lekkich. Pomimo granicznych wartości współczynnika κ/λ (κ/λ = 0,31) w jednej z próbek, dalsza analiza fenotypowa nie potwierdziła klonalnej ekspansji w żadnym z badanych obszarów tarczycy. Wyniki histopatologiczne potwierdziły diagnozę przewlekłego zapalenia tarczycy w obu przypadkach klinicznych. Wnioski: Cytometria przepływowa jest badaniem wiarygodnie uzupełniającym ocenę cytologiczną w diagnostyce różnicowej przewlekłego zapalenia tarczycy i limfoproliferacyjnych chorób tarczycy

Immune checkpoint inhibitors as drugs or drug candidates in neoplastic diseases

Despite of great progress in anti-neoplastic treatment the several solid tumors and hematologic malignancies still remain incurable. Immune system remains under control of several controlling mechanism. Genetic or epigenetic changes in neoplastic cells provide antigen-derived diversity; however, these cells do not initiate immune response. The main mechanism of development of immune resistance by tumor cells seems to be a change in expression of proteins engaged in the immune control point. Immunotherapy with immune checkpoint inhibitors has emerged as promising modality of tumors showing response to several antigens, e.g. anti-CTLA-4 or PD1-PDL1 monoclonal antibodies. In this review we demonstrate the state in the field on this modality of anti-neoplastic treatment

The number and distribution of blood dendritic cells in the epidermis and dermis of healthy human subjects.

Human blood dendritic cells (BDC) can be divided into three subsets: plasmacytoid DC (PDC) and two myeloid subsets--MDC1 and MDC2. Several studies revealed the presence of both MDC and PDC in blood of healthy subjects, however no precise literature data exist on the number and distribution of BDC in the skin. The aim of our study was to assess the number and distribution of BDC and their subtypes in the healthy skin. The-study included 30 healthy volunteers (age 18-51). Punch biopsies were taken from the buttock skin from each subject, and immunofluorescent staining was performed using monoclonal mouse IgG1 antibodies directed against BDCA-1, BDCA-2, BDCA-3 and BDC-4. The BDC were present both in the epidermis and dermis. PDC were detected mainly in the dermis (mean 1.2 cells per field). Myeloid subtypes were observed mainly in the middle layers of the epidermis and in the upper part of the dermis (mean 1.8 cells per field). The detection of blood dendritic cells in the skin proves their role in immune cutaneous surveillance

Towards the Application of Atorvastatin to Intensify Proapoptotic Potential of Conventional Antileukemic Agents In Vitro

It has been previously revealed that statins used at high concentrations display antileukemic potential towards chronic lymphocytic leukemia (CLL) cells. However, their usage alone in clinical practice may be limited due to possible side effects of high doses of these drugs. On the other hand, combined treatment of leukemia with statins and the conventional chemotherapeutics is questionable because of unknown influence of the first on the standard treatment results. This study has revealed that in vitro atorvastatin increases the proapoptotic potential of cladribine and mafosfamide in CLL cells isolated from peripheral blood of patients. Moreover, a preincubation with the above statin sensitizes leukemic cells to CM-induced apoptosis even at small concentrations of the drug. The usage of atorvastatin together with or followed by the conventional chemotherapy should be considered as therapeutic option for the treatment for this leukemia. Interestingly, CM-resistant patients might have the biggest benefits from atorvastatin administration.Grant no. 1407 from the University of Łódź

Comparison of various diagnostic methods in assessing platelet count in patients with immune thrombocytopenia

Introduction: Accurate platelet count (PLTC) in immune thrombocytopenia is important in order to make therapeutic decisions. The basic method of assessing PLTC is peripheral blood morphology with EDTA or with citrate. The older way of assessing PLTC is measurement under the microscope (FONIO), and the newer way is the fluorescent method. The purpose of this study was to compare PLTC methods, and find the most reliable. Material and methods: PLTC was assessed using five methods in adult patients with previously untreated ITP (EDTA, citrate, FONIO, fluorescent, and immunofluorescent methods). Results: 66 patients were enrolled in the study. The median age was 56 and 56% were men. Median PLTC in EDTA was 69 G/L, in citrate 69 G/L, in fluorescence 69 G/L, in FONIO 90 G/L, and in immunofluorescence 83 G/L. A significant difference in PLTC was observed in comparing EDTA to immunofluorescence (53% ±123%), followed by FONIO (51% ±91%). PLTC from immunofluorescence differed from the fluorescent method by 40% ±78%. Conclusions: The most valuable method for obtaining PLTC is the immunofluorescent method. These findings are especially important in helping to make therapeutic decisions during a challenging time for accessing medical care like a pandemic

Diagnostic and therapeutic recommendations of the Polish Society of Hematology and Transfusion Medicine and Polish Adult Leukemia Group-CLL for chronic lymphocytic leukemia in 2016

The management of patients with chronic lymphocytic leukaemia (CLL) is currently undergoing improvements, particularly because of novel therapies. Purine analogs based immuno-chemotherapy, especially fludarabine combined with cyclophosphamide and rituximab (FCR), is still the current standard of care for first line therapy in younger, fit patients. However, its use in older, co-morbid patients is limited, particularly due to high toxicity. In fit patients older than 65 years or/and with previous infections bendamustine and rituximab (BR) should be considered instead of FCR. Recently, in patients with relevant comorbidities chlorambucil and anti CD20 monoclonal antibodies (rituximab, obinutuzumab or ofatumumab) are recommended as the first-line treatment. In addition, in 2014, two novel agents targeting the B cell receptor (BCR) signaling pathway, ibrutinib and idelalisib, were approved for patients with 17p deletion and/or p53 mutations and in the relapsed situation because of high efficacy and a favorable toxicity. Subsequently, ibrutinib has been approved to treat CLL patients regardless of their treatment history. Thus far it is recommended to treat patients with these agents until progression or unacceptable toxicity. The BCL-2 antagonist venetoclax is another oral drug with very promising preliminary data in patients refractory to immunochemotherapy as well as patients harboring del 17p. In 2014, the PTHiT and PALG-CLL group defined guidelines for the diagnosis, prognosis and treatment of CLL. In this article, we present updated recommendations for therapy of CLL