Hany M. Hegab

Effect of high-dose sodium selenite therapy on polymorphonuclear leukocyte apoptosis in non-Hodgkin's lymphoma patients

The present study was undertaken to explore the effect of the administration of high doses of sodium selenite on apoptosis in polymorphonuclear leukocytes in patients with non-Hodgkins lymphoma. Thirty patients with newly diagnosed non-Hodgkins lymphoma were randomly divided into two groups. Group I was treated with chemotherapy and group II received 0.2 mg/kg/d sodium selenite in addition to chemotherapy. Flow cytometry was used for the monitoring of apoptosis on peripheral blood neutrophils at the time of diagnosis and after treatment in both groups of patients. Sodium selenite administration resulted in a significant reduction in neutrophils apoptosis (82±10% vs 32±18%, p<0.05) and this was associated with significant reduction in infection rate following chemotherapy (67% vs 20%, p<0.05). Also, significant improvement in cardiac ejection fraction was observed (62±4% vs 69±5% p<0.05). It is concluded that sodium selenite administration at the dosage chosen acts as a cytoprotective agent, alleviating side effects and immunosuppressive effects of cytotoxic chemotherapeutic agents.

Expression of inhibitor of apoptosis protein (IAP) livin/BIRC7 in acute leukemia in adults: Correlation with prognostic factors and outcome

The clinical relevance of livin/BIRC7 expression is still controversial in different types of malignancies, therefore this study was designed to evaluate the gene expression of livin in Egyptian adult AML and ALL. Livin expression level was higher in patients with unfavorable prognostic factors at diagnosis in both ALL (p=0.002) and AML (p=0.042) and its level was negatively correlated with event free survival (EFS) and overall survival (OS) in both ALL (p<0.001for both) and AML (p=0.001 and 0.023 respectively). This study suggests that livin expression is a novel prognostic marker in adult acute leukemia and thus needs to be incorporated into the patient stratification and treatment protocols.

Prognostic significance of intracellular survivin in myeloid blast cells as an inhibitor of apoptosis in Egyptian adult acute myeloid leukemia patients

Context Abnormalities in the control of apoptosis play an important role in tumorigenesis. Survivin is one of eight members of the inhibitor of apoptosis protein family that regulates and integrates cell division and suppresses apoptosis. Aim The aim of this study was to assess intracellular expression of survivin on malignant myeloid blast cells and its correlation with clinical outcome, overall survival (OS), and other prognostic factors among adult Egyptian patients with acute myeloid leukemia (AML). Settings and design A total of 120 patients with de-novo AML were treated and followed up in Ain Shams University Hospitals Hematology Units and compared with 60 age-matched and sex-matched normal healthy controls. Patients and methods All patients received induction chemotherapy under a 3 + 7 regime, whereas AML-M3 patients received an all-transretinoic acid-based regime. Detection of intracellular survivin antigen in myeloid blast cells was done by flow cytometry on bone marrow samples at diagnosis and after chemotherapy. Results Survivin expression was higher in AML patients at day 0 compared with healthy controls (P = 0.001). The highest survivin level was seen in AML French American British subtypes M5 and M4. A significant positive correlation was found between patients′ age, CD15, CD14, and CD11c expression, whereas negative correlation was found between survivin level and the control group, which included 60 age-matched and sex-matched normal healthy volunteers under complete remission, and event-free survival. Patients with a positive survivin expression have shorter OS compared with patients with a negative survivin expression (log-rank = 3.940, P = 0.047). Conclusion Higher survivin levels at diagnosis predict poor response to chemotherapy and shorter OS (P = 0.016).

Treatment outcome in Egyptian lymphoma patients, 2-year results, single-center experience

Introduction Lymphoma is considered the most common hematologic malignancy in Egypt and accounts for about 8.4% of all new cancer cases annually; however, the treatment outcome needs to be evaluated and compared with those achieved with the standards used worldwide. Patients and methods A retrospective pilot descriptive study of the outcome of patients with lymphoma treated at the Clinical Hematology and Bone Marrow Transplantation Units in Ain Shams University Hospitals over 2 years (2008 and 2009) was carried out. The study included 74 patients, 31 of whom were diagnosed with Hodgkin′s lymphoma (HL) (group I), 10 with indolent non-Hodgkin lymphomas (NHL) (subgroup IIa), and 33 with aggressive NHL (subgroup IIb). Results In this study, NHL was the most common type, found in 58% of the cases, and was more common in older patients; low-grade lymphoma was more common in women and aggressive lymphoma was more common in men. However, HL was found in 42% of cases and was more common in young males. Hepatitis C virus was the most common associated infection; it was detected in 6% of HL and 38% of NHL patients, who were usually in advanced stage disease (80.64% stage III and IV vs. 19.36% stage I and II in HL and 89.19 vs. 10.81% in NHL patients). IPS Hodgkin lymphoma (HL) and International Prognostic Index (IPI) non Hodgkin lymphoma (NHL) were not predictors for treatment response or subsequent relapse. The best results of chemotherapy were achieved using ABVD with IFRT in patients with HL, FC protocol in low-grade NHL, and CHOP-R in high-grade NHL. An overall higher response rate was found in patients with HL compared with NHL patients. ASCT in relapsed patients at the time of the second complete remission did not lead to a significant improvement in disease-free survival or overall survival. Conclusion Although auto-SCT in NHL in our unit was not statistically significant, but it yielded a good result compared with the international one.

Programmed death receptor ligand-1 plasma concentration in chronic myeloid leukemia under first-line tyrosine kinase inhibitor therapy

Background Chronic myeloid leukemia (CML) cells can suppress the immune system by secreting programmed death receptor ligand-1 (PDL-1) that acts as a coinhibitory molecule for T cells leading to T-cell exhaustion and disease progression. Aim The aim of this study was to assess the plasma level of PDL-1 in patients with chronic myelogenous leukemia and its correlation with prognostic parameters and response to first-line therapy. Patients and methods This study was carried out on 40 patients with CML in chronic phase and 40 control healthy participants. Patients with CML were subdivided into three subgroups, including 11 newly diagnosed patients, 17 imatinib mesylate-responding patients, and 12 imatinib-resistant cases. All patients were subjected to laboratory investigations including complete blood count, peripheral blood smear examination, bone marrow aspiration (if indicated), quantitative real-time PCR for Philadelphia chromosome, and plasma PDL-1 measurement by enzyme-linked immune sorbent assay. Results Our results showed high plasma levels of PDL-1 in patients with CML. Plasma PDL-1 levels showed a negative correlation with total lymphocyte count in imatinib-resistant subgroup. Imatinib-resistant subgroup showed a significant decreased level of PDL-1 versus newly diagnosed subgroup of patients with CML. The suggested PDL-1 cut-off value for prediction of patients with CML was 1327.5 ng/l. Conclusion Patients with chronic-phase CML (newly diagnosed, imatinib responding, and imatinib resistant) showed a highly significant increased PDL-1 level compared with the control group. Increased plasma PDL-1 level is a predictive risk factor for CML incidence and disease progression.

Expression of thioredoxin-1 (TXN) and its relation with oxidative DNA damage and treatment outcome in adult AML and ALL: A comparative study.

Objective: Thioredoxin-1 (TXN) is a key element in the elimination of reactive oxygen species as well as activation of tumor suppressor genes and DNA repair enzymes. Several studies showed that TXN was over expressed in solid tumors and this was correlated to poorer prognosis. However, TXN expression has been insufficiently studied, particularly in newly diagnosed adult acute leukemia. Methods: This study was designed to evaluate the gene expression of TXN in acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL) adult patients and to investigate its association with oxidative DNA damage. The expression of TXN was analyzed using quantitative reverse transcriptase-polymerase chain reaction while oxidative DNA damage was evaluated by measuring serum 8-hydroxy-2-deoxyguanosine (8-OHdG) by enzyme-linked immunosorbent assay and strand breaks by the comet assay. Results: We found that TXN was under expressed in both AML and ALL groups (P < 0.001 for both) as compared to the control group. Also TXN expression level was negatively correlated with serum 8-OHdG and tail moment in both AML (P = 0.042 and 0.047, respectively) and ALL (P < 0.001 and P = 0.02, respectively) while it showed no correlation with treatment outcome in either groups. Discussion: This study suggests that TXN expression is hindered in adult acute leukemia which augments oxidative DNA damage and hence mutagenesis. Conclusion: This study provides a new insight into the pathogenesis of acute leukemia and suggests TXN as a new screening test for the risk for acute leukemia.

Cryopreservative against noncryopreservative therapy in autologous hematopoietic stem cell transplantation (the Egyptian experience)

Introduction Autologous peripheral blood stem cell transplantation is a ′rescue′ of patients′ self hematopoietic stem cells from the myeloablative effects of chemotherapy or irradiation. Cryopreservation of hematopoietic stem cells using 10% dimethyl sulfoxide as a cryoprotectant under liquid nitrogen storage conditions (−196°C) for long-term usage is a well-established procedure, whereas liquid preservation of stem cells is usually performed for storage at 4°C for 36-96 h. The aim of the study was to compare the outcome of autologous stem cell transplantation using cryopreserved or noncryopreserved stem cells. Patients and methods Twenty adult patients younger than 60 years of age were enrolled in this study. They had undergone autologous peripheral stem cell transplantation. They had been stratified into two groups: 10 patients received cryopreserved autologous peripheral stem cell transplantation (PBSCT) and the remaining 10 patients received noncryopreserved autologous PBSCT. Results When we compared the cryopreserved and the noncryopreserved groups for the clinical outcome, there had been a longer overall survival and disease-free survival in favor of the cryopreserved group, but this had not been translated into statistically significant values. In addition, there was no significant difference with regard to the recurrence of disease. However, the noncryopreserved group had a shorter hospital stay and entailed less cost than the cryopreserved group (8149

High-Dose Sodium Selenite Can Induce Apoptosis of Lymphoma Cells in Adult Patients with Non-Hodgkin’s Lymphoma

against 8900

The Impact of High-dose Sodium Selenite Therapy on Bcl-2 Expression in Adult Non-Hodgkin’s Lymphoma Patients: Correlation with Response and Survival

, respectively). This could be attributed to the fact that liquid nitrogen was not used, and the shorter hospital stay (P = 0.000) lowered the cost for medications, laboratory tests, and procedures. Cryopreserved therapy was found to be cost-effective with regard to keeping the patient alive in those who cannot tolerate proceeding to autologous stem cell transplant immediately after mobilization. Conclusion Noncryopreserved therapy required a lesser number of aphaeresis sessions, was associated with a shorter hospital stay, was less costly than cryopreserved therapy, and it yielded the possibility of transplantation in patients with hepatitis without the need for buying a special liquid-nitrogen tank.