Dariusz Szczepanek

Imbalance in circulatory iNKT, Th17 and T regulatory cell frequencies in patients with B‑cell non‑Hodgkin's lymphoma

T cells are important in B-cell non-Hodgkins lymphoma immunity, however the function of T cell subsets, including natural killer (iNKT), T helper (Th)17, and T regulatory cells remains to be elucidated. The present study analyzed the frequencies of iNKT, Th17 and T regulatory cells in the peripheral blood of 41 patients with B-cell non-Hodgkin lymphoma at diagnosis, then during and following immunochemotherapy R-CHOP/R-CVP. At lymphoma diagnosis, iNKT and Th17 frequencies were decreased and T regulatory cell frequencies were increased compared with healthy control group. The Th17 cell percentage was lower in patients with a worse prognosis and at a more advanced clinical stage and in contrast, the percentage of T regulatory cells was increased in patients at advanced stages of lymphoma, compared to earlier stages. There was an increase of iNKT and Th17 cells following R-CHOP/R-CVP therapy. In patients that responded, both prior to and following-treatment, percentages of iNKT and Th17 were higher and T regulatory cells were lower compared with patients with subsequent disease progression. Taken together, the results obtained demonstrated the opposing effects of T cell subsets in B-cell lymphoma immunity, with iNKT and Th17 inhibiting and T regulatory cells enhancing tumor growth. These alterations may be caused by malignant B-cells, however there may also be an axis of inverse feedback between T regulatory cells and their interaction with Th17 and iNKT cells.

Znaczenie dokomorowych iniekcji w leczeniu pierwotnego chłoniaka ośrodkowego układu nerwowego

STRESZCZENIE Systemowe leczenie pierwotnych chloniakow ośrodkowego ukladu nerwowego (OUN) z zastosowaniem wysokich dawek metotreksatu (MTX) oraz arabinozydu cytozyny (Ara-C) w chwili obecnej uznawane jest za najbardziej efektywny zestaw lekow cytostatycznych. Aktualnie badana jest mozliwośc poprawy efektywności terapii poprzez dodatkowe iniekcje dokomorowe lekow cytostatycznych.

Primary central nervous system lymphoma as a neurosurgical problem

Primary central nervous system lymphoma (PCNSL) comprises around 3-5% of primary central nervous system (CNS) tumours and around 1% of all non-Hodgkin lymphoma (NHL). Diffuse large B-cell lymphoma (DLBCL) is the most common histological type. High effectiveness of chemo- and radiotherapy for PCNSL regrettably does not eliminate significant risks of recurrence for CNS tumours. That results in higher interest in other treatment options, including surgical procedures. PCNSL remains in the scope of interest for many specialists and neurosurgeons seem to play a more important role.

Therapy - Related Myeloid Neoplasm in a Patient with Prior Treatment for Chronic Lymphocytic Leukemia: A Case Report

Background: Acute myeloid leukemia or myelodysplastic syndrome, during the course of chronic lymphocytic leukemia, is a rare entity. In such a situation, most previous cases were therapy-related after treatment. However, in very rare cases, acute myeloid leukemia has been diagnosed in untreated patients with chronic lymphocytic leukemia. Materials and Methods: In this paper, we present the case-study of a 60-year old woman who was diagnosed six years previously as being afflicted with chronic lymphocytic leukemia with no chromosomal changes. She was successfully treated with fludarabine in combination with cyclophosphamide and rituximab, and she obtained complete remission, yet with incomplete recovery. Subsequently, three years later, she was re-admitted to hospital with deep pancytopenia. Her bone marrow biopsy then revealed that 52% of her blasts cells demonstrated a myelomonocytic immunophenotype, albeit with no chronic lymphocytic leukemia cell clone, showing the following complex chromosomal abnormalities: 45~47, XX, del(5)(q13q33), trisomy 8, trisomy 20, monosomy 21, +mar[cp12]/46, XX. Thus, a diagnosis was made of acute myelomonocytic leukemia preceded by a transforming myelodysplastic syndrome. The patient received induction chemotherapy and obtained complete remission. Unfortunately, one month after completion of her consolidation regimen, a relapse occurred. She died 8 months post-diagnosis of AML. Conclusion: In this case study, we diagnosed therapy-related acute myeloid leukemia. Of note, the theory of a common stem cell malignancy and the coexistence of two malignant clones seem not to be applied in the presented case. This is because an acute myeloid leukemia clone was not seen in her bone marrow, nor was peripheral blood evidenced at the time of her diagnosis of chronic lymphocytic leukemia.

Assessment of micro RNAs expression in leukemic cells as prognostic markers in chronic lymphocytic leukemia: micro RNAs can predict survival in a course of the disease

Numerous genetic alterations predicting prognosis and clinical outcome are revealed recently in chronic lymphocytic leukemia (CLL). Among them the deregulated expression of micro RNAs that can induce tumor growth, or act as tumor suppressors seem to be of great importance. This study aimed to analyze the possible role of chosen micro RNAs as markers of prognosis in patients with CLL. We assessed the expression of miR-21, miR-34a, miR-181a, miR-199a/b and miR-221 in previously separated leukemic cells with the use of qRQ-PCR technique at the moment of diagnosis. The results were then analyzed in regards to presence of prognostic factors, clinical data and the end points like progression free survival (PFS), time to progression (TP) and overall survival time (OS). We detected significant correlations between expression of the analyzed micro RNAs and CLL prognostic markers particularly as far as miR-221 and miR-181a were concerned. The subsequent analysis revealed that high expression of miR-34a and miR-181a as well as low miR-21 expression indicated longer TTP, while miR-221 was predictor of OS. The obtained results prove the role of micro RNAs as CLL prognostic markers, particularly as factors predicting survival in a course of the disease.

Intraventricular treatment of secondary central nervous system lymphoma – Case study and literature overview

Secondary nervous system lymphoma (SCNSL) is a rare extranodal form of non-Hodgkin lymphoma (NHL). This applies to a particular form of lymphoma that does not originally derive from the central nervous system (CNS); it can be both an isolated form of relapse or a systemic part of disease progression. Due to poor prognosis and a lack of established algorithms of therapeutic procedures, it is a big challenge for physicians from many specializations. In our study, we present an interesting case of a patient with a relapsed form of SCNSL for whom a unique form of treatment was used - intraventricular administration of rituximab and methotrexate.

Size and location correlations with higher rupture risk of intracranial aneurysms

AIM The purpose of this study was to investigate the impact of size and location of the intracranial aneurysm on rupture probability. MATERIAL AND METHODS 265 patients with diagnosis of intracranial aneurysms were admitted to the department from January 2012 to December 2013. The characteristic of aneurysm, such as median size, location, single and multiple aneurysms and presentation were retrospectively reviewed using cerebral angiography reports. RESULTS There were 265 patients admitted with the diagnosis of intracranial aneurysms, 193 with single and 72 with multiple aneurysms. Among them there were 197 women (74,3%) and 68 men (25,7%). The total number of aneurysms harbored by the patients with multiple aneurysms were 184. Among all patients 96 had ruptured aneurysm, most of them located at the AComA and the minority of ruptured aneurysms were located at the ICA and MCA, In most cases the size of ruptured aneurysm was smaller than 10 mm. CONCLUSION The location of an aneurysm is an important factor allowing to predict the rupture probability and to plan proper treatment. The size of the aneurysm is also very useful predictor especially correlated with the location but the impact on rupture probability still needs further examination.

Surface CD200 and CD200R antigens on lymphocytes in advanced gastric cancer: a new potential target for immunotherapy

Introduction Gastric cancer (GC) is one of the leading causes of cancer death worldwide. The membrane glycoprotein CD200, widely expressed on multiple cells/tissues, uses a structurally similar receptor (CD200R), delivering immunoregulatory signals. There is evidence that CD200/CD200R signaling suppresses anti-tumor responses in different types of malignancies. Little is known about the CD200/CD200R pathway in GC. The aim of the study was to evaluate the frequencies of CD200+ and CD200R+ lymphocytes in patients with GC. Material and methods Forty patients primarily diagnosed with GC and 20 healthy volunteers (control group) were enrolled. The viable peripheral blood lymphocytes underwent labeling with fluorochrome-conjugated monoclonal antibodies and were analyzed using a flow cytometer. Results In the GC group, the percentages of T CD3+, CD3+/CD4+, and CD3+/CD8+ cells expressing CD200 antigen were higher than in the control group (p < 0.00013, p < 0.0004, and p < 0.0006, respectively). In the GC group, the frequencies of T CD3+, CD3+/CD4+ and CD3+/CD8+ cells expressing CD200R were lower than in the control group (p < 0.0009, p < 0.004, and p < 0.002, respectively). The percentage of B CD19+/CD200+ lymphocytes was higher in GC patients than in the control group (p < 0.00005). Lower frequency of B CD19+/CD200R+ cells was observed in GC patients compared to the control group (p < 0.0001). No differences in the frequencies of CD200+ and CD200R+ lymphocytes were found in relation to either UICC stage or histological grading of the tumors. Conclusions For GC pathogenesis, deregulation of the CD200/CD200R axis is important. High percentages of lymphocytes with CD200 expression may contribute to the continuous T cell activation and development of chronic inflammation and influence gastric carcinogenesis.

The clinical importance of changes in Treg and Th17 lymphocyte subsets in splenectomized patients after spleen injury

BACKGROUND Splenectomized patients are more prone to bacterial infections due to their immunocompromised status. Little is known about the role of T helper 17 (Th17) and T regulatory cells (Treg) in the immune system of patients after the removal of the spleen. OBJECTIVES The aim of the present study was to analyze possible changes in CD4+ lymphocyte T subsets, especially Treg and Th17, in patients who had undergone splenectomy. MATERIAL AND METHODS The study included a group of 67 male patients (41.74 ±16.22 years). All patients had undergone splenectomy because of spleen injury. Mean time elapsed from splenectomy to analysis was 9.1 ±4.6 years. Control samples were obtained from 20 male healthy volunteers. The percentages and absolute counts of Th17 and Treg were measured using the flow cytometry method. RESULTS The analysis of the antibody titer against 23 serotypes of Streptococcus pneumoniae (S. pneumoniae) in the splenectomized patients revealed its elevated values compared to controls (p = 0.0016). Higher percentages and absolute counts of Treg cells were found in the splenectomized group vs controls (p < 0.000007). Lower percentages and absolute counts of the Th17 subset were found in the study group vs controls (p < 0.000002 and p < 0.00006, respectively). The Treg cell percentage was positively correlated with the antibody titer against S. pneumoniae (p < 0.02). Th17 cells were reversely correlated with the antibody titer (p < 0.004 and p < 0.001 for absolute counts and percentage values, respectively). The Th17 subset values were significantly lower in the splenectomized patients who reported a higher frequency of upper respiratory tract infections (URTI) (p < 0.0001). No correlations were found between the time elapsed since splenectomy and the Treg or Th17 cell values in the study group. CONCLUSIONS Splenectomy results in an important deterioration of the Treg/Th17 cell balance with a predominance of immunoregulatory Tregs, which can contribute to insufficient immune response to infection.

Richter syndrome: A rare complication of chronic lymphocyticleukemia or small lymphocytic lymphoma

BACKGROUND Richters syndrome (RS) is a rare complication with an unfavorable prognosis, in which chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) transform into a more aggressive type of lymphoma, most commonly into diffuse large B cell lymphoma (DLBCL) or less often into Hodgkins lymphoma (HL). OBJECTIVES The objective of this research paper was to present a retrospective analysis of patients with CLL/SLL whose disease transformed into RS. MATERIAL AND METHODS The study included 217 patients (100 women and 107 men) with CLL/SLL diagnosed in the years 2006-2015 at the Department of Hematooncology and Bone Marrow Transplantation of the Medical University of Lublin, which transformed into RS. We analyzed clinical, laboratory, immunophenotypic (ZAP-70 and CD38 expression), histopathological, and genetic data (del(17p), del(11q)), which was collected at the time of CLL/SLL diagnosis, and some which was collected at the time of transformation. RESULTS Richters syndrome was diagnosed in 4.6% of all CLL and SLL patients. The group of patients with RS consisted of 9 patients with primary CLL and 1 patient with a diagnosis of SLL (8 patients with transformation into DLBCL and 2 patients with transformation into HL). Leukemic lymphocytes showed evidence of peripheral blood lymphocyte membrane expression of ZAP70+/CD38+ (1 patient), of ZAP-70+/CD38- (3 patients), of ZAP-70-/CD38- (1 patient), and of ZAP-70-/CD38+ (5 patients). The deletion of 11q (del(11q)) was documented in 2 patients. In 4 cases, the location of RS was extremely rare (the thyroid gland, liver, skin, bladder, and central nervous system). CONCLUSIONS Richters syndrome is a rare, but probable complication of CLL/SLL with an unfavorable prognosis, and it should be taken into account at every stage of the disease, particularly when the course of the disease is aggressive.