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  Citation statistics : Table of Contents
   2015| October-December  | Volume 40 | Issue 4  
    Online since November 23, 2015

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Tissue factor-positive monocytes in children with sickle cell disease: relation to vaso-occlusive crisis
Mohamed A Soliman, Seham M Ragab
October-December 2015, 40(4):177-184
Background Hemostatic abnormalities are well documented in sickle cell disease (SCD). Nevertheless, whether these perturbations could contribute toward sickle vasculopathy is still not clear. Aim To evaluate tissue factor (TF) expression (CD142) on monocytes in children with SCD and correlate the results with the clinical state and some inflammatory and coagulation activation markers. Patients and methods This study included 24 children with SCD in steady state, 24 in painful crisis, and 20 healthy age-matched and sex-matched children as controls. The relevant data including the pain rate were retrieved from patients' files. For each participant, complete blood count, prothrombin time (PT%), activated partial thromboplastin time (aPTT), fibrinogen, d-dimer, thrombin-antithrombin complex, and quantitative C-reactive protein were assayed. TF expression on monocytes was analyzed by flow cytometry. Results TF-positive monocytes were significantly higher in both patient groups compared with the controls, being higher in patients in painful crisis (2.06 ± 0.64, 8.01 ± 1.53, and 13.5 ± 4.3 for the controls, steady-state group, and the painful crisis group, respectively, P < 0.0001 in all comparisons). The same pattern was found for all tested inflammatory and coagulation markers, except PT and aPTT. In the painful crisis group, TF monocytes expression was correlated positively with the pain rate and all markers of inflammation and coagulation, except PT, aPTT, and thrombin-antithrombin complex, with an inverse correlation with hemoglobin and red blood cells. Conclusion Collectively, these results confirm the prognostic significance of evaluation of TF-positive monocytes in SCD children.
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TET2 expression in a cohort of Egyptian acute myeloid leukemia patients
Nahla A Hamed, Nabil A El Halawani, Heba S Kassem, Mona W Ayad, Enas A Dammag
October-December 2015, 40(4):159-165
Ten-eleven translocation 2 gene (TET2) expression plays a crucial role in DNA methylation and hematopoietic stem cell functions. The prognostic relevance of the TET2 mutation in cytogenetically normal acute myeloid leukemia (AML) patients is still not well established. The aim of the present study was to determine the level of TET2 expression in AML patients, its prognostic significance, and its relation to cytogenetics. We studied TET2 gene expression by real-time PCR in 33 AML patients and 34 healthy controls matched for age and sex. The median age of AML patients at presentation was 40 years, with a female to male ratio of 1.06 : 1. A total of 87.9% were de-novo AML and 12.1% were chronic myeloid leukemia in blastic crisis. In all, 66.6% of cases had normal cytogenetics. Underexpression of the TET2 gene was present in 90.6% (0.3098 ± 0.3846) of the patients. TET2 expression was not affected by age (P = 0.609) or cytogenetic findings (P = 0.057). Yet, it was correlated inversely with pretreatment white blood cell count (rs = −0.366, P = 0.04). It also correlated with lower remission rates (P = 0.002) and relapse (P = 0.000). TET2 probably plays a role in the pathogenesis and progression of AML. This can play a role in targeted therapy in the future. Further studies are recommended to assess TET2 expression in response to hypomethylating agents to determine its predictive role in response to therapy using these agents.
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Prognostic significance of intracellular survivin in myeloid blast cells as an inhibitor of apoptosis in Egyptian adult acute myeloid leukemia patients
Mohamed Azzazi, Soha Ezz El-Arab, Hany M Hegab, Walaa Elsalakawy, Rasha Ibrahim, Mohammad Shazly
October-December 2015, 40(4):166-174
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).
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Rituximab-containing chemotherapy in pregnancy with malignancy
Prakas K Mandal, Tuphan K Dolai, Sudipta Bose, Maitreyee Bhattacharyya
October-December 2015, 40(4):201-202
Non-Hodgkin lymphoma diagnosed during pregnancy often has an aggressive histology, with diffuse large B-cell or peripheral T-cell lymphomas being most common in this context. Aggressive lymphomas during pregnancy present a difficult challenge in diagnosis, especially in staging by means of radiological evaluation. The aim of the treatment is to give the mother the best chance for cure but at the same time with minimal harm to the fetus. Most cytotoxic agents, including rituximab, cross the human placenta and reach the fetus. Rituximab-based chemotherapy (R-CHOP) is now considered the standard of care and generally considered safe for the treatment of aggressive lymphomas during pregnancy except during the first trimester.
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Zinc and malondialdehyde levels among Egyptian patients with acute myeloid leukemia and their relation with disease phenotype and genotype
Inas A Asfour, Maryse S Ayoub, Amro M.S. El-Ghammaz, Ibtesam M Khalifa
October-December 2015, 40(4):153-158
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.
  - 1,314 3,478
VTD in newly diagnosed myeloma: an institutional experience
Meet Kumar, Ashutosh Panigrahi, Tuphan K Dolai, Rajib De, Prakas K Mandal, Prantar Chakrabarti
October-December 2015, 40(4):175-176
Background Myeloma management has evolved over the years with logarithmic expansion of available treatment options. The treatment algorithms are also changing because of the better responses obtained with newer agents. Bortezomib, thalidomide and dexamathasone (also known as VTD) is one such therapy that has shown improved long term outcomes. Materials and methods We conducted a single-center, retrospective analysis of all myeloma patients treated with VTD chemotherapy. Results An overall response achieved was 85.7% with 40% CR. Conclusion We conclude VTD is an effective chemotherapy regimen in newly-diagnosed myeloma patients.
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The utility of the CKD-EPI formula for determination of glomerular filtration rate in Nigerians with sickle cell disease
John C Aneke, Anthony A Oyekunle, Adegbola O Adegoke, Abubakr A Sanusi, Emmanuel C Okocha, Norah O Akinola, Muheez A Durosinmi
October-December 2015, 40(4):185-189
Background and objective Predictive formulae for the calculation of estimated glomerular filtration rate (eGFR) are increasingly being used in clinical practice for monitoring of renal function. We evaluated the usefulness of the CKD-EPI formula for eGFR in a population of Nigerian patients with sickle cell disease (SCD). Patients and methods One hundred SCD patients were prospectively studied. Relevant information, including age, weight and sex, was obtained from the participants, whereas creatinine clearance was measured following a 24-h urine collection. The Cockcroft-Gault (C-G) and the CKD-EPI formulae were thereafter used to calculate the glomerular filtration rate (GFR) for all participants. SPSS (version 17) and Microsoft Excel 2007 computer software were used for all data collection and analyses. A P-value of less than 0.05 was considered significant. Results The comparison of measured GFR versus eGFR by the C-G and CKD-EPI formulae in homozygous haemoglobin SS (HbSS) patients yielded correlation coefficients (r values) of 0.667 (P < 0.001) and 0.598 (P < 0.001), respectively. Correspondingly, among the heterozygous haemoglobin S + C (HbSC) patients, measured GFR versus eGFR resulted in r values of 0.819 (P < 0.001) and 0.848 (P < 0.001), respectively. Conclusion The CKD-EPI formula is a good measure of eGFR in our population of SCD patients; however, it did not perform significantly better than the C-G formula.
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Differences between nucleophosmin isoforms in de-novo acute myeloid leukemia: possible implications in developing targeted therapy for acute myeloid leukemia with normal karyotype
Safaa A. A. Khaled, John Burthem, El Badry E Abu-ElNoor, Lobna F ELTony, Sohier M Ahmed, Hanan M Ahmed
October-December 2015, 40(4):190-194
Background The current approach of treating de-novo acute myeloid leukemia (AML) is still ineffective. This is in part due to the clinical and molecular diversity of the disease. Accordingly, development of new effective targeted therapies for AML is mandatory. The current study investigated the differences between nucleophosmin (NPM) isoforms in de-novo AML. The work focused on AML with a normal karyotype as it constitutes 45% of AMLs and bears mutated nucleophosmin (mNPM). The main objective was to identify the active region in the NPM molecule to be targeted with a specific therapy. Materials and methods In this study human leukemia cell lines HL60 and OCI-AML3 were used as models for AMLs bearing wild-type NPM and mNPM, respectively. The study was conducted through indirect immunofluorescence and immunoblotting techniques. The obtained results were presented and analyzed with appropriate computer software. Results and conclusion The analyzed data proved, for the first time, that mNPM is phosphorylated at Thr199. As cdk2 is the main mediator of Thr199 phosphorylation, we speculated that a specific cdk2 inhibitor could be highly valuable as targeted therapy in de-novo AML with a normal karyotype. However, further experimental work in the presence of cdk2 inhibitors is needed.
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Demographic, clinical, and hematologic characteristics of patients with chronic myeloid leukemia in Upper Egypt: association with treatment responses
Safaa A. A. Khaled, Nashwa M. A. Abd El Aziz
October-December 2015, 40(4):195-200
Background and objectives Chronic myeloid leukemia (CML) is a relatively indolent hematologic malignancy that carries poor prognosis if left untreated. With the recent advances in treatment options for CML, therapy could be tailored to each patient based on patient and/or disease characteristics. This research aimed to study the characteristics of patients with CML in Upper Egypt and to investigate their influence on various therapeutic responses. Patients and methods A retrospective study was conducted at the Hematology Unit of Assiut University Hospital and South Egypt Cancer Institute. The demographic, clinical, hematologic, and follow-up data of patients with CML were extracted from hospital records at both Assiut University Hospital and South Egypt Cancer Institute during the period from January 2007 to December 2012, representing a total of 180 patients. Records with incomplete data or unavailable follow-up were excluded from the study. Results and conclusion The median age of participants was 42 years, and the male-to-female ratio was 1 : 1.7. The Eastern Cooperative Oncology Group Performance Status was the most important effector of both hematologic and therapeutic responses (P = 0.000), followed by the phase of the disease (P = 0.000 and 0.017, respectively), and lastly the Philadelphia chromosome (P = 0.07 and 0.000, respectively). Moreover, leukocytosis was associated with poor hematologic and cytogenetic responses (r = 0.19, P = 0.000; r = −0.16, P = 0.05). A small proportion of patients achieved complete hematologic and cytogenetic responses (45 and 52%, respectively). These novel findings may reflect a trend of young age, female-predominant CML in Upper Egypt and could be attributed to the ethnic and socioeconomic differences of our patients compared with those in similar studies.
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