The evaluation of the outcome in myelodysplastic patients by using non-cytogenetic prognostic scores.

UNLABELLED: Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic stem cell disorders; they are characterized by ineffective hematopoiesis and a predilection to the development of acute myeloid leukemia (AML). For a rapid evaluation of the outcome in myelodysplastic patients non-cytogenetic prognostic scores can be used. AIM: This study proposed to demonstrate that age and gender are important factors in the outcome of the patients diagnosed with myelodysplastic syndrome. MATERIALS AND METHODS: This study was conducted in the Department of Hematology of the Emergency University Hospital Bucharest during October 2008 and October 2012. RESULTS: Male sex and age higher than 60 years are associated with high risk in the studied cases by using the Spanish prognostic score. According to Goasguen score: male sex and age, patients older than 60 years, present characteristics associated with an intermediate risk. Based on the Dusseldorf score, age over 60 years and female gender were associated with pronounced risk in the examined group. By examining the Bournemouth score in our group, we found that age > 60 years correlated with a higher frequency of risk, but no significant differences regarding the sex of patients were observed. CONCLUSIONS: We concluded that age > 60 years and male gender are important predisposing factors in the survival.

CD 200 - A useful marker in chronic B lymphoprolipherative disorders.

Background: The diagnosis and management of the patients with chronic lymphoproliferative diseases have become dependent on immunological criteria. Flow cytometry immunophenotyping is used for rapid and specific diagnosis but there are cases when we are not facing a typical immunophenotype, so there is a constant need to find new markers and new combinations of markers that would allow the improvement and the development of our diagnosis. Aim: Our aim was to evaluate CD 200 expression in different B-cell chronic lymphoproliferative disorders. CD200 is a membrane glycoprotein belonging to the immunoglobulin superfamily and the over-expression of CD200 has been reported in a number of malignancies, including CLL, as well as on cancer stem cells. Methods: We analyzed the CD200 expression in 122 patients diagnosed with chronic lymphoproliferative disorders (100 patients with CLL, 10 patients with splenic marginal zone lymphoma (SMZL), 10 patients with MCL and 2 patients with hairy cell leukemia), in the Department of Hematology of the University Emergency Hospital, Bucharest. We performed immunophenotypical analysis of peripheral blood and bone marrow aspiration on BD FACS Calibur flowcytometer. Results: CD200 was brightly expressed in all 100 CLL patients (100%). In SMZL patients, CD200 was dim positive (40%-60%), in patients with HCL. CD200 was also bright positive (96% and 97%) and in patients with MCL CD200 was negative (1-10%); CD 200 was significantly higher in CLL patients compared with other B-cell chronic lymphoproliferative disorders. We found 14 patients with CD19, CD5 positive population and CD23- , but with high expression of CD 200. Cyclin D1 was negative on bone marrow biopsy in 13/14 of these patients. (1/14 patients were without bone marrow involvement); Conclusions: CD200 has a great impact in diagnosing B- chronic lymphoproliferative disorders, especially when we want to determine the origin of a CD19, CD5 positive population and distinguish between CLL and MCL. CD 23 is a reliable marker in those cases, but, as we showed, CD23 might have a lower specificity than CD200 for CLL. We added CD200 in our panels in order to diagnose chronic lymphoproliferative disorders, not to replace CD 23, but to improve and save time in our diagnostic process. The high expression of CD200 in CLL and HCL could open the option for new- targeted therapy (anti-CD200).

The lymphocyte immunophenotypical pattern in chronic lymphocytic leukemia associated with hepatitis viral infections.

BACKGROUND: Chronic lymphoproliferative disorders (CLD) are frequently found in patients with hepatitis viral infections, which can lead to changes in pathogenesis. Hepatitis viruses are hepatotrope viruses, potentially lymphotrope and also potentially oncogenic (hepatocellular carcinoma) viruses. HBV and HCV are involved in autoimmune disorders and in the ethiopathogeny of chronic lymphoproliferative disorders. AIM: Detection of immunophenotype changes of malignant lymphocytes in CLD--especially CLL--associated with hepatitis viral infections. MATERIALS AND METHODS: Bone marrow aspirate, peripheral blood samples on EDTA were available for analysis from 58 patients from a follow-up schedule of the Department of Hematology SUUB from March 2008 until June 2009. The patients were diagnosed with chronic lymphoproliferative disorders associated with hepatitis virus B/C/D infections. A group of 28 consecutive unselected patients with CLL who met the diagnostic criteria of the National Cancer Institute-Working Group (NCI NCIWG), and associated hepatitis viral infection (v-CLL) were studied for the expression of several immunophenotypical markers, in comparison to CLL patients without viral infection (control group). Immunophenotyping analysis was performed on a FACS Calibur flowcytometer with a large panel according to EGIL/WHO recommendations. The diagnosis was completed after the histological and immunochemical analysis from tumoral lesions. RESULTS: Demographics characteristics--male/female ratio 1/2, average age 64 years. Disease type: 90% B-CLD, 5% T-CLD, 5% Hodgkin's disease. The viral infections: 58.53% HCV, 34.41% HBV, 2.43% HBV+HDV, 2.43% HCV+HDV, 2.43% HBV+HCV+HDV. We found in CLL with viral coinfection (v-CLL) cases an elevated expression of B-cell markers--CD19 (Md95/92), CD20 (Md 90/39), CD79b (Md58/31), CD23 (Md67/37). Poor prognosis markers have a higher expression in v-CLL: CD38 (Md49/24), Bcl2 (Md 46/5), cyclin D19 (Md 11/0.5). No change in ZAP-70 expression was observed: Md 59.5/59.1. DISCUSSIONS: Hepatitis viruses could be involved in the pathogenesis of CLD, but as a trigger for a more aggressive outcome. Higher expression of B-cell markers CD19, CD20 in CLL with viral infection suggests a change to atypical CLL, sustained by elevated expression of known poor prognosis markers bcl-2, cyclin D1 and CD38. Lack of ZAP-70 expression could be explained by a strong correlation with a basic unmutated IgVH status, not related to the viral infection. We found a higher frequency of HCV infection in patients with CLD and especially in CLL patients, which were analyzed extensively for immunophenotypical changes. In the present study, we demonstrated that this CD5+ B cell population with clonal expansion, defining CLL patients, has a different immunophenotype, probably related to the hepatitis viral infection.