Lymphoproliferative Malignant Diseases Research Articles

Correlation between CD200 expression and oxidant-antioxidant status in newly diagnosed B-chronic lymphocytic leukemia patients

B cell chronic lymphocytic leukemia (B-CLL) is the highest incidence of lymphoproliferative malignant disease in most adults in the western world. Due to the importance of the pathogenicity and risk factors of this disease, this study was designed to analyze the expression the pattern of CD200 by flow cytometer immunophenotyping (FCI) and the association between this marker and some clinical features and oxidant-antioxidant status in B-chronic lymphocytic leukemia patients. This study was conducted on 60 newly diagnostic patients with B-CLL and 30 apparently healthy individuals as control group. The socio-demographic information including (age and sex) and clinical data were also collected in period 20 February 2021 to 25 December. The result of statistical analysis of the present study showed that out of the 60 patients, 39 were male and 21 females, with 30 controls (12 males and 18 females). The mean age of adults patients was (64.04 ± 5.6) years, and the adults control mean age of (63.33 ± 4.70) years therefore, there was a higher prevalence p value ≤0.05 of newly diagnosed CLL patients in males (65.0 %) in compared with females (35.0 %).

Autoimmune and lymphoproliferative malignant diseases associated with Epstein-Barr viral infection

Currently, in medical practice, there is a high interest in diseases caused by herpes viruses, among them the Epstein-Barr virus (EBV) occupies the leading place. Almost 90% of the worlds population over the age of 40 are infected with VEB. In patients of the first two years, the proportion of asymptomatic carriage reaches 90%, and at the age of 2-10 30-50%. The article considers current data on the impact of EBV on cellular and humoral immunity, its connection with autoimmune and lymphoproliferative diseases. EBV has been shown to play a significant role in the onset of oncological diseases such as Hodgkins lymphoma, Burkitts lymphoma, nasopharyngeal carcinomas, as well as autoimmune diseases systemic lupus erythematosus, rheumatoid arthritis, Sjogrenʼs syndrome, autoimmune hepatitis, lymphoid interstitial hepatitis, lymphoid interstitial syndrome. The results of studies over the past 5 years of cases of activation of autoimmune processes associated with EBV infection, as well as predisposing factors underlying these manifestations, are presented. Due to the fact that the autoimmune effect of EBV infection is manifested in various organs and tissues, this problem is multidisciplinary, affecting such fields of medicine as pediatrics, infectious diseases, endocrinology, oncology, gynecology, ophthalmology, gastroenterology, etc.

PB1963 CHARACTERISTICS OF NEWLY DIAGNOSED AUTOIMMUNE HEMOLYTIC ANEMIA: 5‐YEARS OF SINGLE‐CENTER EXPERIENCE

Background:Autoimmune hemolytic anemia (AIHA) is a rare autoimmune disease in which red blood cells (RBC) are targeted by autoantibodies confirmed with positive direct antiglobulin test (DAT), resulting in premature destruction of RBC. AIHA may be subdivided into warm antibody AIHA (wAIHA) and cold antibody AIHA (cAIHA), and also to primary and secondary depending on the presence of an underlying disorder. In addition to that, patients may have positive DAT but without features of hemolysis, and some of them will later develop AIHA.Aims:The aim of this study was to analyze characteristics of newly diagnosed DAT positive AIHA patients during the 5 years period in our tertiary center, as well to assess DAT positive patients without features of AIHA.Methods:This was a single‐center retrospective cohort study performed at the University Hospital Center (UHC) Zagreb, Zagreb, Croatia, Department of Internal Medicine, Division of Hematology. We included data for all consecutive adult patients with a newly diagnosis of DAT positive AIHA between 2014 and 2018, and also all DAT positive patients without features of hemolysis in that time period. This study was approved by the UHC Ethical Committee. Descriptive statistics was performed and included means ± SD or median (range) as appropriate for continuous variables and frequency (percentage) for categorical variables.Results:The data from 56 patients (50% women) with newly diagnosed DAT positive AIHA during the study period were analyzed. The median age at time of AIHA diagnosis was 67 years (range 22–90 years). Majority of AIHA was wAIHA (51 (91.1%) patients). AIHA was considered primary in only 14 (25%) patients and was associated with an underlying disorder in 42 (75%) patients. The various disorders were associated with secondary wAIHA, the most frequently B‐cell lymphoproliferative malignant diseases (33%), solid tumors (9.8%), myelodisplastic syndrome (9.8%) and autoimmune diseases (9.8%). Median hemoglobin level at the AIHA diagnosis was 71 g/L. 82.1% of patients received RBC transfusion. Seven (12.5%) patients did not require immunosuppressive treatment and other received mostly corticosteroids as the 1st line of therapy. Rituximab received 9 patients (17.6%) with wAIHA, mostly as the 2nd line of treatment. Eight patients (14.3%) with AIHA developed thrombosis (7 with wAIHA and 1 with cAIHA). During the 5‐years study period additional 120 patients with DAT positive results but without signs of hemolysis were detected.Summary/Conclusion:Data from our 5‐years single centre experience with AIHA are comparable with literature data. Majority of patients had secondary AIHA and wAIHA. Rituximab is used mostly as the second‐line treatment and corticosteroid‐sparing agent for wAIHA. Significant number of patients with DAT positive results but without features of hemolysis was detected, and they need to be closely monitored for possible development of AIHA.

A naturally processed HLA-DR-bound peptide from the IL-9 receptor alpha of HTLV-1-transformed T cells serves as a T helper epitope.

Human T cell leukemia virus type 1 (HTLV-1) induced adult T cell leukemia/lymphoma (ATLL) is usually a fatal lymphoproliferative malignant disease. Thus, the enhancement of T cell immunity to ATLL through the development of therapeutic vaccines using characterized T cell peptide epitopes could be of value. We isolated and characterized HLA-DR-bound peptides from HTLV-1-transformed T cells by fractionating on reverse-phase high performance liquid chromatography and Edman NH(2)-terminal sequencing and were able to identify five independent peptide sequences. One of the identified peptide sequences corresponded to a fragment of the human interleukin-9 receptor alpha (IL-9Rα), which is commonly expressed by HTLV-1-infected T cell lymphoma cells. Using a synthetic peptide corresponding to the identified IL-9Rα sequence, we generated antigen-specific CD4 helper T lymphocytes in vitro, which were restricted by HLA-DR15 or HLA-DR53 molecules and could recognize and kill HTLV-1+, IL-9Rα+T cell lymphoma cells. These results indicate that IL-9Rα functions as T cell leukemia/lymphoma-associated antigen for CD4 T cells and that synthetic peptides such as the one described here could be used for T cell-based immunotherapy against IL-9Rα positive ATLL.

IL-18 Serum Concentration Is Markedly Elevated in Acute EBV Infection and Can Serve as a Marker for Disease Severity

Epstein Barr virus (EBV)-related diseases encompass both acute infections that result in acute infectious mononucleosis and chronic infections that result in lymphoproliferative malignant diseases. While classical inflammatory parameters such as C-reactive protein (CRP) have proven their usefulness during bacterial and fungal infections, they are often low and nondiscriminatory in viral infections. Here, we show that IL-18 is markedly elevated during acute EBV infections and EBV-associated diseases, while ferritin concentrations are also elevated during acute EBV infection and correlate with IL-18. Therefore, IL-18 and ferritin may represent infection markers for viral infections such as EBV, similar to CRP for bacterial infections.

Meningeal carcinomatosis in solid tumors

The involvement of the leptomeninges by metastatic tumors can be observed in solid tumors, in which case it is termed meningeal carcinomatosis (MC), and in lymphoproliferative malignant disease. It is more common in breast and lung cancer, as well as melanoma, with adenocarcinoma being the most frequent histological type. MC is usually a late event, with disseminated and progressive disease already present and, it is characterized by multifocal neurological signs and symptoms. Diagnosis is based on the evaluation of clinical presentation, cerebrospinal fluid and neuroimaging studies. The better systemic disease control is observed with new therapeutic agents, and the development of neuroimaging methods is responsible for the increasing incidence of such metastatic evolution. Intrathecal chemotherapy is generally the treatment of choice, although frequently palliative. Prognosis is guarded, although a higher performance status may indicate a subgroup of patients with a more favorable outcome.

Intrathecal chemotherapy for treatment of leptomeningeal dissemination of metastatic tumours

Neoplastic meningitis consists of diffuse involvement of the leptomeninges by infiltrating cancer cells, and can be caused by systemic or primary CNS tumours, such as solid cancers or lymphoproliferative malignant disease. Neoplastic meningitis is characterised by multifocal neurological signs and symptoms. Thus, careful neurological examination is needed for diagnosis of secondary diffuse involvement. Survival of patients with neoplastic meningitis is short (3-4 months), although some patients have long-lasting remission. Because most patients with neoplastic meningitis have diffuse systemic disease, treatment is typically palliative. However, more aggressive treatments are available to low-risk patients, which could increase survival. Therefore, identification of low-risk patients is important. Intrathecal chemotherapy is currently the main treatment for patients with neoplastic meningitis, but optimum anticancer chemotherapy is being studied.

In vitroPeptide Immunization of Target Tax Protein Human T-Cell Leukemia Virus Type 1–Specific CD4+ Helper T Lymphocytes

Adult T-cell leukemia/lymphoma induced by human T-cell leukemia virus type 1 (HTLV-1) is usually a fatal lymphoproliferative malignant disease. HTLV-1 Tax protein plays a critical role in HTLV-1-associated leukemogenesis and is an attractive target for vaccine development. Although HTLV-1 Tax is the most dominant antigen for HTLV-1-specific CD8(+) CTLs in HTLV-1-infected individuals, few epitopes recognized by CD4(+) helper T lymphocytes in HTLV-1 Tax protein have been described. The aim of the present study was to study T-helper-cell responses to HTLV-1 Tax and to identify naturally processed MHC class II-restricted epitopes that could be used for vaccine development. An MHC class II binding peptide algorithm was used to predict potential T-helper cell epitope peptides from HTLV-1 Tax. We assessed the ability of the corresponding peptides to elicit helper T-cell responses by in vitro vaccination of purified CD4(+) T lymphocytes. Peptides Tax(191-205) and Tax(305-319) were effective in inducing T-helper-cell responses. Although Tax(191-205) was restricted by the HLA-DR1 and DR9 alleles, responses to Tax(305-319) were restricted by either DR15 or DQ9. Both these epitopes were found to be naturally processed by HTLV-1(+) T-cell lymphoma cells and by autologous antigen-presenting cells that were pulsed with HTLV-1 Tax(+) tumor lysates. Notably, the two newly identified helper T-cell epitopes are found to lie proximal to known CTL epitopes, which will facilitate the development of prophylactic peptide-based vaccine capable of inducing simultaneous CTL and T-helper responses. Our data suggest that HTLV-1 Tax protein could serve as tumor-associated antigen for CD4(+) helper T cells and that the present epitopes might be used for T-cell-based immunotherapy against tumors expressing HTLV-1.

Malignant disease of the lymphoid system in immunological perspective

The study of the structure of the lymphoid system has been an essential element in the overall progress of immunobiology. Study of the normal immune system, and especially study of immune deficiency disease, has revealed a remarkable degree of complexity within the lymphoid system, particularly at the cellular level. This complexity precludes the precise or definitive characterization of lymphoproliferative malignant disease by morphological criteria alone. However, new methodologies now available can be used to identify distinct lymphocyte subpopulations, each population possessing a characteristic set of markers or functions. As a result of these recent advances, the definition of lymphoproliferative malignant disease in immunological terms is entering a highly productive period.