Inas A. Asfour

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.

Changing therapy from Glivec ® to a "copy" imatinib results in a worsening of chronic myeloid leukemia disease status: two case reports

IntroductionImatinib mesylate (Glivec®/Gleevec®) is the standard first-line therapy for the treatment of chronic myeloid leukemia due to its high hematologic, cytogenetic, and molecular response rates and favorable long-term safety profile. A copy version of imatinib is currently available in several countries. We report on two cases of CML who were originally treated with Glivec in Egypt and subsequently switched to the copy drugCase presentationCase one was a 35-year old female with chronic myeloid leukemia in blast crisis who began treatment with combination chemotherapy and Glivec. The patient achieved and maintained a complete hematologic response and continued on Glivec 400 mg/day. In March 2007, she was switched to the copy drug In September 2007, the patient presented in hematologic relapse. At this time, treatment with chemotherapy in combination with Glivec 400 mg/day was resumed. The patient quickly achieved, and maintained, complete hematologic response on Glivec 400 mg/day. The second patient was a 64-year old male with chronic myeloid leukemia in blast crisis who began treatment with truncated chemotherapy in combination with Glivec 400 mg/day. After 6 months, the patient achieved a partial hematologic response and continued on alternating cycles of chemotherapy with continuous administration of Glivec 400 mg/day. The patient received Glivec from January 2006 to February 2007, after which time he was switched to the copy drug. In November 2007, he presented with upper gastrointestinal bleeding and multiple gastric erosions and died the same day.ConclusionThe safety and efficacy of the copy drug has not been established in randomized clinical trials. It is unknown whether patients, who respond to Glivec and then switch to copy versions of imatinib, will tolerate the copy drug and maintain their response.

CXCR4 (CD184) expression on stem cell harvest and CD34+ cells post-transplant

OBJECTIVES/BACKGROUND CXCR4 is a receptor for stromal-derived factor-1 (SDF-1), a molecule that has a chemotactic activity for lymphocytes and is important in homing of hematopoietic stem cells to their adult marrow. We evaluated the CXCR4 (CD184) expression in the harvest cells and in the post-transplant bone marrow (BM) and its relation to engraftment, as determined by the consensus criteria and chimerism. METHODS This is a prospective study which included 30 patients undergoing hematopoietic stem cell transplantation; 15 patients received autograft and 15 patients received allograft on dates between January 2012 and May 2014. We assessed CD184 (CXCR4) using flow cytometry in the harvest cells together with post-transplant BM assessment on Day 28 and Day 90 for complete morphologic, molecular studies, and detection of CD184 expression on CD34+ cells with chimerism studies on total peripheral blood mononuclear cells. RESULTS Diagnoses of the enrolled patients were as follows: seven (24.1%) with acute myeloid leukemia, eight (27.6%) with multiple myeloma, four (13.8%) with acute lymphoblastic leukemia, three (10.3%) with non-Hodgkin lymphoma, two (6.9%) with myelodysplastic syndromes, two (6.9%) with aplastic anemia, two (6.9%) with chronic myeloid leukemia, one (3.4%) with Hodgkin lymphoma, and one (3.4%) with plasmacytomas. One patient died and was excluded from the study because there were not enough data about engraftment. There was no statistical significance between the level of CD184 in stem cell harvest and the prediction of successful engraftment (p>0.05) as well as in Day 28 BM sample (p>0.05), whereas there was a statistical significance between the level of CD184 in Day 90 BM sample and the occurrence of successful engraftment (p=0.002). CONCLUSION SDF-1/CXCR4 axis plays a crucial role in engraftment; however, more studies are warranted to assess their expression post-transplant. Evaluating the ligand (chemokine, SDF-1) or its receptor (CXCR4) may serve as potential surrogate markers for assessment of engraftment.

Zinc and malondialdehyde levels among Egyptian patients with acute myeloid leukemia and their relation with disease phenotype and genotype

Objectives This study was conducted to evaluate serum zinc and plasma malondialdehyde (MDA) levels in de-novo acute myeloid leukemia (AML) before and after induction chemotherapy and their relation with AML phenotype and genotype. Materials and methods Twenty-five AML patients were subjected to serum zinc evaluation using flame atomic absorption spectrophotometry and plasma MDA evaluation using colorimetric method at day 1 before induction chemotherapy and at day 21 after induction chemotherapy. Results Pretreatment MDA levels were higher in patients in comparison with controls (P = 0.03). Pretreatment zinc levels differed significantly compared with post-treatment levels (P = 0.005). The percentage of bone marrow infiltration by blasts at diagnosis correlated inversely with zinc levels (P = 0.011) and positively with MDA levels (P = 0.041). Finally, pretreatment MDA levels were higher among patients harboring adverse cytogenetics (P = 0.004). Conclusion The elevated plasma MDA status at diagnosis in AML patients correlates with a higher tumor burden in the bone marrow and adverse cytogenetic risk.

Study of CD123 (interleukin-3 receptor alpha Chain) and nuclear factor kappa B in adult acute myeloid leukemia patients

Background: The genomic alterations in acute myeloid leukemia (AML) affect the function of signaling molecules, transcription factors, and growth factor receptors besides they influence the response to treatment. Interleukin-3 receptor alpha chain (CD123) is overexpressed in about 45% of AML, this phenomenon was associated with high blast cell counts at diagnosis, with a worse prognosis. The transcription nuclear factor kappa B (NF-κB) can intervene in oncogenesis through its capacity to regulate the expression of a large number of genes that regulate apoptosis, cell proliferation, and differentiation. This study aimed to assess the relationship between CD123 expression and NF-κB level, in adult patients with AML at presentation and after induction therapy together with a well-known diagnostic and prognostic factors in AML. The study was conducted on forty adult newly diagnosed AML (group A) as well as twenty adult subjects who were hemato-oncologically free, as a control group (group B). Bone marrow (BM) examination and immunophenotyping by flow cytometry (FCM) on BM aspirate, for CD123 and quantitation of NF-κB in BM samples using ELISA (at three levels: Plasma, cytoplasmic and nuclear fraction of blasts, accordingly cytoplasmic/nuclear ratio) were performed for all studied subjects. In addition, levels of CD123 on blast cells and NF-κB were evaluated at D28 for remitted and resistant cases. All patients were positive for CD123 by FCM on BM blasts at time of diagnosis. The median cell counts expressing CD123 was 52.9 (34.4-75.6). Positive expression of CD123 was ≥20%, while in the control subjects CD123 expression was 25.1 (16.9-59.3), with significant decrease in CD123 expression after therapy, Besides, CD123 was also significantly higher in resistant patients compared to remitted patients ( P = 0.009). As regard NF-κB, it was significantly higher in AML patients compared to control subjects at the three levels (plasma - cytoplasmic fraction - nuclear fraction) with a significant decrease after therapy. It was found that those NF-κB levels detected at follow-up (D28) on BM expression were significantly higher in resistant patients compared to remitted patients. While only The follow-up results, showed a highly significant positive correlation between CD123 expression on blast cells level and NF-κB plasma level alone ( r = 0.587, P = 0.007) while there was not any correlation between CD123 and other two NF-κB levels neither at diagnosis nor at the follow-up. Conclusion: These data suggest that the correlation between CD123 and NF-κB was identified in variable results, and further elucidation of this role is likely to have important implications.