Tamer A Elbedewy

The Utility and Applicability of Chronic Myeloid Leukemia Scoring Systems for Predicting the Prognosis of Egyptian Patients on Imatinib: Retrospective Study

Background: Chronic myeloid leukemia (CML) is myeloproliferative clonal neoplasm. Imatinib has greatly improved CML prognosis. Many prognostic scoring systems have been developed for CML risk stratification. In clinical practice, 3 systems are widely used: Sokal, Hasford and European Treatment Outcome Study (EUTOS). Recently, EUTOS long-term survival (ELTS) score is the first long-term scoring system that considered specifically CML-related death. Therefore, the aim of the present study was to validate the effectiveness of Sokal, Hasford, EUTOS and ELTS scoring systems in predicting the outcome in Egyptian CML-chronic phase (CML-CP) patients treated with imatinib. Patients and methods: Retrospective study performed on 167 patients with CML-CP who were treated with imatinib. Using the Sokal, Hasford, EUTOS and ELTS scores, we divided the patients into each risk groups. Results: Significant differences in event free survival (EFS), time without progression (TWP) and overall survival (OS) prediction between the Sokal, Hasford and ELTS risk groups, but no significant difference among the EUTOS score risk groups. Conclusion: Our study indicates that Sokal, Hasford and ELTS scoring systems but not the EUTOS score are effective in predicting early treatment response, EFS, TWP and OS for Egyptian CML patients treated with imatinib

Prevalence and chemotherapy-induced reactivation of occult hepatitis B virus among hepatitis B surface antigen negative patients with diffuse large B-cell lymphoma: significance of hepatitis B core antibodies screening.

BACKGROUND Occult hepatitis B infection (OBI) is characterized by negative hepatitis B surface antigen (HBsAg) and detectable hepatitis B virus (HBV)-DNA in the liver and/or serum, with or without hepatitis B core antibody (anti-HBc). Anti-HBc is the most sensitive marker of previous HBV. HBV reactivation in patients under immunosuppressive treatment is life-threatening, occurring in both overt and occult HBV especially in hematological malignancies. AIM OF THE WORK To evaluate the prevalence and chemotherapy-induced reactivation of OBI among hepatitis B surface antigen negative patients with diffuse large B-cell lymphoma (DLBCL) patients and to determine the significance of anti-HBc screening among this group of patients before receiving chemotherapy. PATIENTS AND METHODS This cross-sectional study included 72 DLBCL patients negative for HBsAg, HBsAb and hepatitis C virus antibodies (anti-HCV). Patients were subjected to investigations including anti-HBc. All patients underwent alanine transaminase (ALT) monitoring before each cycle of chemotherapy and monthly for 12 months after the end of chemotherapy. Patients with suspected OBI were tested for HBV-DNA using real-time polymerase chain reaction (PCR). RESULTS Anti-HBc was detected in 10 of 72 HBsAg negative sera (13.89%) (95% confidence interval 6.9-22.2%). Five of the 10 anti-HBc positive patients in this study had OBI reactivation. CONCLUSION The study concluded that anti-HBc screening is mandatory before chemotherapy. HBsAg-negative/anti-HBc-positive patients should be closely observed for signs of HBV reactivation through the regular monitoring of ALT. Prophylaxis lamivudine is recommended for anti-HBc positive patients before chemotherapy.

Serum cystatin-C and urinary N-acetyl-β-d-glucosaminidase as biomarkers for early renal dysfunction in adult Egyptian patients with β-thalassemia major

Background/aims β-Thalassemia syndromes are the most common inherited hemoglobinopathies. In Egypt, 1000/1.5 million/year live borns suffered from thalassemia. β-Thalassemia major (β-TM) is the most severe form. Advances in the care of patients with β-TM, have allowed previously unrecognized complications to emerge, including several renal abnormalities. Therefore, the aim of the present study is to investigate the presence of glomerular and/or tubular dysfunctions in adults with β-TM, using biomarkers of glomerular and tubular dysfunctions. Subjects and methods Forty patients with β-TM (group I) were selected with 20 age-matched and sex-matched healthy participants as a control (group II). Patients were subjected to full medical history taking and complete clinical examination. Serum cystatin-C and urinary N-acetyl-β-d-glucosaminidase (UNAG) levels were measured. Results Significantly higher levels of serum cystatin-C and UNAG in thalassemic patients were observed when compared with the control group. Significantly higher levels were observed for serum cystatin-C and UNAG in patients with renal affection, poorly chelated and inadequately transfused patients. A significant positive correlation between serum cystatin-C and serum ferritin was observed and significantly negative correlations between serum cystatin-C on one hand and pretransfusional hemoglobin and estimated glomerular filtration rate on the other hand were observed. A significantly positive correlation between UNAG and the urinary albumin creatinine ratio (ACR) and significantly negative correlations between UNAG on one hand and pretransfusional hemoglobin and estimated glomerular filtration rate on the other hand were observed. Conclusion β-TM patients had glomerular and tubular dysfunctions. Serum cystatin-C and UNAG are promising biomarkers for monitoring glomerular and tubular dysfunction.

Prognostic role of tissue expression and serum level of YKL-40 in patients with diffuse large B-cell lymphoma

Background Serum YKL-40 levels are increased in various inflammatory disorders and a wide range of malignancies. Moreover, these elevated levels correlate with poor prognosis of patients with cancer, suggestive of YKL-40 as a prognostic biomarker. The effect of YKL-40 on non-Hodgkin lymphoma prognosis has not been fully explained. Aim The aim of this article was to study the serum levels and expression of YKL-40 in tissue specimens of patients with diffuse large B-cell lymphoma (DLBCL) for assessing its prognostic value and shedding light on their effect on survival. Patients and methods The study included 60 patients with DLBCL. Enzyme-linked immunosorbent assay was used to assess the serum YKL-40 levels. Immunohistochemical staining was used to detect YKL-40 protein expression in lymphoma specimens. Results YKL-40 serum levels were significantly higher in patients with DLBCL when compared with the control group. YKL-40 protein was expressed in 66.67% of examined specimens. Receiver–operator curve analysis showed serum YKL-40 at a cutoff value of greater than or equal to 95.5 ng/ml had a sensitivity of 70% and a specificity of 95% for DLBCL diagnosis. In patients with DLBCL, progression-free and overall survival rates significantly decreased with increased serum levels of YKL-40 above the cutoff level as well as in YKL-40 positive expressed patients. Conclusion Serum YKL-40 and its tissue expression could be a valuable prognostic marker in patients with DLBCL.

Serum monoclonal and polyclonal free light chains in newly diagnosed Egyptian patients with diffuse large B-cell lymphoma: their impact on event-free and overall survival

Background/aim Diffuse large B-cell lymphoma (DLBCL) constitutes the largest subtype of B-cell non-Hodgkin′s lymphomas. The prognostic ability of the International Prognostic Index in the era of immunochemotherapy is modest. New prognostic biomarkers are mandatory to provide new insights into the risk stratification of DLBCL. Nowadays, serum-free light chain (sFLC) assay is being applied to hematologic non-plasma cell B-cell lymphoid malignancies. The aim of our work was to investigate the prevalence and prognostic value of elevated sFLC (monoclonal and polyclonal) in DLBCL and their impact on event-free survival (EFS) and overall survival (OS). Patients and methods This cohort study included 58 patients with DLBCL. Pretreatment serum samples were taken to detect κ and λ sFLCs with enzyme-linked immunosorbent assay. Patients were followed up every 3 months and computed tomographic scan was done every 6 months for 24 months after treatment. EFS and OS were estimated. Results Twenty-four patients (41.38%) had elevated κ or λ sFLC. Thirteen patients (22.41%) and 11 patients (18.97%) had monoclonal and polyclonal elevated sFLC, respectively. EFS and OS significantly decreased in patients with elevated sFLC and in those with abnormal sFLC ratio (monoclonal elevated sFLC). OS significantly decreased in patients with monoclonal elevated sFLC when compared with those with polyclonal elevated sFLC, but there was no difference between monoclonal and polyclonal elevated sFLC patients as regards EFS. Conclusion Elevated sFLC and abnormal sFLC ratio (monoclonal elevated sFLC) correlate with disease outcome (EFS and OS). There was no difference between monoclonal and polyclonal elevated sFLC as regards EFS but there was significant difference as regards OS.

Serum thrombopoietin and platelet antibodies in thrombocytopenic patients with chronic hepatitis C virus: clinical application of platelet indices

Background Chronic hepatitis C virus (HCV) infection is prevalent in 160 million individuals worldwide. Egypt has the highest prevalence of HCV in the world. HCV is known to cause thrombocytopenia even in the absence of overt hepatic disease. The pathophysiology of thrombocytopenia with chronic HCV is complex. Aims To evaluate serum thrombopoietin (TPO) and platelet antibodies in thrombocytopenic patients with chronic HCV and to assess the diagnostic utility of mean platelet volume (MPV) and platelet distribution width (PDW). Patients and methods The present study included 70 patients with chronic HCV with thrombocytopenia divided into two groups; 20 age-matched and sex-matched HCV patients without thrombocytopenia were also included as controls. Serum TPO, platelet autoantibodies, MPV, and PDW were measured in all participants. Results A significantly lower serum TPO level and platelet count were found with advancing degree of liver fibrosis and activity. Significantly higher MPV and PDW were found in patients with antiplatelet autoantibodies formation. The platelet count showed significant positive correlations with TPO level, MPV, and PDW, and inverse correlations with aspartate aminotransferase, alanine aminotransferase, and viral load. Conclusion The dominant mechanism in mild thrombocytopenic HCV patients was the formation of antiplatelet autoantibodies, whereas in moderate to severe thrombocytopenic patients, the dominant mechanism was combined bone marrow affection and formation of antiplatelet autoantibodies. Serum TPO level was decreased in patients with HCV-induced thrombocytopenia. MPV and PDW may be used as indicators for the dominant mechanism. Egyptian J Haematol 41:-0 ͹ 2016 The Egyptian Society of Haematology.

Prevalence and significance of hepatitis-B core antibodies among hepatitis B surface antigen-negative Egyptian patients on hemodialysis in Al-Gharbia governorate

Background/aims Hepatitis B virus (HBV) infection in hemodialysis (HD) patients represents a serious problem due to the immunosuppressive effect of renal failure and the susceptibility for de-novo HBV infection during HD with high morbidity and mortality. Occult hepatitis B virus infection (OBI) is defined as the presence of HBV-DNA in the serum and/or the liver in the absence of hepatitis B surface antigen (HBsAg). The strategy of combined screening for HBsAg and hepatitis B core antibody (anti-HBc) can virtually eradicate blood-transmitted HBV. The aim of this study was to evaluate the presence of anti-HBc among Egyptian regular HD adult patients and to determine the presence or absence of HBV-DNA in the serum samples from HBsAg-negative, anti-HBc-positive regular HD adult patients using the polymerase chain reaction (PCR) method to assess the magnitude of OBI in these patients. Patients and methods This cross-sectional study included 90 regular HD patients negative for HBsAg and anti-hepatitis C virus. Patients were investigated for anti-HBc, and samples of anti-HBc-positive patients were tested for HBV-DNA using real-time PCR. Results Among the 90 HBsAg-negative sera, anti-HBc was detected in 17 sera (18.9%). Eleven anti-HBc-positive patients were anti-HBs-positive. HBV-DNA was detected in seven of those 17 anti-HBc-positive patients (41.2%) (7.8% of all patients). Conclusion The overall prevalence of OBI in adult Egyptian regular HD patients is 7.8% in Al-Gharbia Governorate.

Prevalence and significance of hepatitis B core antibodies among hepatitis B surface antigen-negative Egyptian polytransfused adult patients

Background/aims Blood transfusion is a well-established line of therapy associated with risk of infection transmission. Occult hepatitis B virus (HBV) infection is defined as the presence of HBV-DNA in the serum and/or the liver in the absence of hepatitis B surface antigen (HBsAg). Combined screening of HBsAg and hepatitis B core antibody (anti-HBc) can virtually eradicate blood-transmitted HBV. The aim of this study was to evaluate the presence of anti-HBc among Egyptian polytransfused adult patients and to determine the presence or absence of HBV-DNA in the serum samples of HBsAg-negative, anti-HBc-positive polytransfused adult patients using the polymerized chain reaction (PCR) method to assess the magnitude of occult HBV infection in these patients. Patients and methods This cross-sectional study included 79 polytransfused patients negative for HBsAg, HBsAb, and anti-hepatitis C virus. Patients were investigated for anti-HBc and samples of anti-HBc-positive patients were tested for HBV-DNA using real-time PCR. Results Among the 79 HBsAg-negative sera, anti-HBc was detected in 12 of 79 (15.19%) cases. All anti-HBc-positive sera were anti-HBs-negative. HBV-DNA was detected in five of 12 (41.67%) cases. Occult HBV infection was present in 6.33% of patients. Conclusion The overall prevalence of occult HBV in adult Egyptian polytransfused patients on regular blood transfusion is 6.33%.

Pulmonary hypertension in adult Egyptian patients with b-thalassemia major: correlation with natural anticoagulant levels

Background/aim Thalassemia constitutes a heterogeneous group of inherited anemia. In Egypt, 1000/1.5 million live births per year suffer from thalassemia. b-Thalassemia major (b-TM) is characterized by absent or reduced synthesis of b hemoglobin chains. The incidence and pathophysiology of pulmonary hypertension (PH) in patients with b-TM is not clear. The hypercoagulable state in thalassemia enhances the risk of thrombosis, such as pulmonary embolism. The aim of the present study was to investigate the prevalence of PH in adults with b-TM and investigate the role of protein C, protein S, and antithrombin III deficiencies in the pathogenesis of PH in adults with b-TM. Subjects and methods Forty patients with b-TM (group I) were selected, along with 20 age-matched and sex-matched healthy individuals as controls (group II). Patients were subjected to full medical history and complete clinical examination. Plasma protein C, protein S, and antithrombin III assays were measured using ELISA. Doppler echocardiography was used for estimation of systolic pulmonary artery pressure (sPAP). Results PH was diagnosed in 16 (40%) patients. Significantly higher levels of sPAP were found in poorly chelated and inadequately transfused patients. Significantly lower levels of protein C, protein S, and antithrombin III were found in patients with PH. There was significant negative correlation between protein C, protein S, and antithrombin III and sPAP. Conclusion Significant decrease in protein C, protein S, and antithrombin III was found in b-TM, especially in patients with PH, which might suggest the role of the hypercoagulable state in the pathogenesis of PH in b-TM.

Prognostic utility of CD184 in acute myeloid leukemia

Background Chemokine induce directional migration of cells toward a gradient of chemotactic cytokines (chemotaxsis). CD184 is a chemokine receptor which regulates the localization of leukemic cells, and most leukemic cells respond to it, with increased adhesion, survival and proliferation. Aim The work was conducted to evaluate the role of CD184 in newly diagnosed patients with acute myeloid leukemia. Subject and method Eighty patients presented with de novo AML. Based upon the distribution of CD184 expression in our patients′ population, we defined groups with low CD184 expression as group I (MFIR 4 to 8), intermediate CD184 expression as group II (MFIR 9 to 20), and high CD184 expression as group III (MFIR more than 21). Patients with acute myeloid leukemia were studied at first diagnosis and were previously untreated. After diagnosis, patients received chemotherapy and they were followed up for periods ranged of 24 months with special attention to clinical and laboratory markers of remission and relapse, taking care to estimate the date of first complete remission, date of relapse, death or last seen alive. Results patients were divided according to CD184 expression (MFIR) into 3 groups; group (I) with low expression (MFIRs ≤9) had a mean of 5.04 ± 1.48, group (II) with intermediate expression (MFIRs between 9 to 20) had a mean of 10.03 ± 0.45, and group (III) with high expression (MFIRs ≥20) had a mean of 30.25 ± 6.17. In the present study, we found no relation between CD184 expression levels in AML patients and the age of patients. Also, no significant relation was found between CD184 expression levels and the presence or absence of hepatosplenomegally and lymphadenopathy (P > 0.05 ). As regards to haematological data and MFIR of CD184 expression in AML patients, the mean leukocytic count was significantly lower in group (I) than in group (II) and group (III), and leucocytic count was significantly related to CD184 expression in the three groups. Also, the percentage of blasts in peripheral blood and bone marrow was significantly related to CD184 expression with P value < 0.05 while no significant relation was found with haemoglobin or platelets (P > 0.05). As regards to prognosis and MFIR of CD184 expression, group (I) showed 70% remission, 20% relapse and 10% death, while group (II) showed 33.33% remission and 66.67% relapse and group (III) showed 100% deaths meaning that high and intermediate CD184 expression were associated with low rates of remission and high frequency of relapse and death. We can conclude that CD184 expression can represent a useful prognostic tool for AML patients.