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   Table of Contents - Current issue
Coverpage
April-June 2018
Volume 43 | Issue 2
Page Nos. 45-95

Online since Tuesday, August 7, 2018

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ORIGINAL ARTICLES  

Screening of single nucleotide polymorphism in CD95 (APO-1/FAS) promoter region (G-1377A) in children with acute leukemia p. 45
Dilara F Akin, Didem T Özkan, Emin Kürekçi, Nejat Akar
DOI:10.4103/ejh.ejh_55_17  
Background CD95 is a cell surface receptor involved in apoptotic signal transmission. Deregulation of this pathway results in downregulation of apoptosis and subsequent persistence of a malignant clone. A single nucleotide polymorphism resulting in guanine-to-adenine (G>A) transition in the CD95 promoter region (position −1377) is thought to reduce stimulatory protein 1 transcription factor binding and decrease CD95 expression. The purpose of this study is to examine a genetic polymorphism in the core promoter region of CD95 and to evaluate association between its frequency and clinical findings. Patients and methods G-1377A in the CD95 promoter region was genotyped by polymerase chain reaction and restriction endonuclease analysis finally were sequenced by Sanger Sequecing. Results Among 146 patients, CD95 G-1377A (rs2234767) single nucleotide polymorphism carriers frequencies have been identified as 25% (n=37) GA and AA 4% (n=6). This polymorphism of the distribution of the CD95 gene in children with acute leukemia will be a guide for future studies. Conclusion This polymorphism of the distribution of the CD95 gene in children with acute leukemia will be a guide for future studies.
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High expression of activation-induced cytidine deaminase mRNA can predict early-stage progression and poor responsiveness to treatment in chronic lymphocytic leukemia p. 49
Mohamed A.M El-Menoufy, Mohamed A.R Ahmed
DOI:10.4103/ejh.ejh_35_17  
Background Chronic lymphocytic leukemia (CLL) is a clinically heterogeneous disease. Some patients exhibit an indolent disease without requiring therapy, whereas others show rapidly progression and die within months. The Rai and Binet staging systems are unable to predict disease progression in the early stages. Aim The aim of this study was to evaluate the clinical value of activation-induced cytidinedeaminase (AID) mRNA expression in predicting disease progression in early stages and response to therapy in later stages of CLL. Patients and Methods We assessed AID mRNA expression by quantitative real-time PCR in 42 patients with B-CLL. Results High AID expression was associated with shorter duration for the need to start antileukemic treatment in patients with earlystage CLL. Moreover, high AID expression was also found in patients not achieving complete remission or nonresponding to treatment. Conclusion AID could be used to predict early disease progression and was shown to be relevant in predicting responsiveness to antileukemic treatment in CLL cases.
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Alteration of trace elements and T-cell subsets in patients with β-thalassemia major: influence of high ferritin level p. 55
Asmaa Nafady, Eman Nasreldin, Hanaa Nafady-Hego, Khalid A Nasif, Eman A Abd-Elmawgoud, Mohammed M Sayed
DOI:10.4103/ejh.ejh_3_18  
Introduction Oxidative damage is believed to be found in transfusion-dependent patients with β-thalassemia. Oxidative damage may trigger an immune response and affect the trace elements. Objective The aim of this study was to investigate the effect of iron transfusional overload on lymphocytes and on the serum trace elements. Patients and methods A total of 53 patients with thalassemia were divided into two groups according to the ferritin level (≥1000 and <1000). The patients’ levels of zinc, copper, calcium, magnesium, and phosphorous, as well as the proportion of T cells, B cells, T-helper cells, cytotoxic T cells, and natural killer cells, were compared with 40 healthy volunteers (control). Results Our finding showed that although the levels of hemoglobin, hematocrit, mean corpuscular volume, and mean corpuscular hemoglobin were significantly lower in all patients compared with control, their levels were comparable among patients with different ferritin level. Moreover, although serum zinc, calcium, and magnesium levels were significantly lower in patients, the serum level of phosphorous was significantly higher in patients, and serum copper showed an insignificant difference, and their levels did not differ among patients with different ferritin level. The proportion of total T cells and cytotoxic T cells was significantly increased in patients with higher ferritin level compared with control. On the contrary, the percentage of T-helper cells was lower in all patients regardless of the ferritin status. The percentages of B cells and natural killer cells were comparable among the study group. Conclusion Despite the slight effect of high ferritin on trace elements and lymphocyte subsets, insignificant findings necessitate further expanded study with larger sample size.
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Hypoparathyroidism in children with β-thalassemia major and its relation to iron chelation therapy p. 63
Lerine Bahy El-Din, Fatma S.E Ebeid, Nadin N Toaima, Walaa W Ibrahim
DOI:10.4103/ejh.ejh_42_17  
Background β-Thalassemia major (BTM) constitutes a major public health problem in Egypt. Early diagnosis of hypoparathyroidism (HPT) could prevent other severe disorders such as seizures, osteopenia, and osteoporosis. Objective The aim of this study was to determine the prevalence of HPT in patients with BTM and its relation to iron chelation therapy. Patients and methods This is a cross-sectional study that included 60 patients with transfusion-dependent BTM who were regularly attending the Pediatrics Hematology Clinic, Ain Shams University. The male–female ratio was 1 : 1.2. Their mean age was 12.47±3.63 years. The recruited patients were subjected to thorough clinical assessment with special emphasis on demographic characteristics, chelation and transfusion therapy, calcium consumption, age of onset of HPT, any symptoms of hypocalcemia, and presence of other complications. Laboratory investigations included hemoglobin electrophoresis, serum ferritin, serum calcium, serum phosphate, and serum parathyroid hormone levels. Results A total of 26 patients were on single iron chelation therapy, whereas 34 patients were on combination therapy. The prevalence of HPT was relatively high, as 20% were diagnosed as having HPT. There was a high prevalence of asymptomatic hypocalcemia (51.6%), including 12 patients who had HPT and 19 patients who had hypocalcemia without HPT. Moreover, 14 patients had hyperphosphatemia without HPT. Although HPT was less common in those treated with single-agent desferrioxamine, asymptomatic hypocalcemia was more prevalent in those who were treated with desferrioxamine iron chelation. In contract, hyperphosphatemia was more common in those on combination therapy. Conclusion HPT is not an uncommon complication of BTM, as well as the asymptomatic hypocalcemia, which necessitates early diagnosis and management.
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Prognostic value of renin gene expression in acute myeloid leukemia p. 69
Nahela A Shalaby, Deena S Eissa, Naglaa M Hassan, Nevin M.Al Azhary, Amany A Saleh
DOI:10.4103/ejh.ejh_48_17  
Background The majority of acute myeloid leukemia (AML) patients respond to initial chemotherapy, but only a minority of cases achieves long-term survival. Renin, as a part of the renin–angiotensin system, is directly linked to the activities of hematopoietic cytokines during normal hematopoiesis and in myeloproliferative neoplasms. In some hematological malignancies, blast cells have been observed to express renin, which is not found in normal marrow. Aim The aim of this was to study the expression of the renin gene as a prognostic marker in AML. Patients and methods Renin expression was measured in 45 AML patients and five controls by using quantitative real-time reverse-transcriptase PCR. Results Renin expression was detected in 93.3% of AML patients at diagnosis and 100% at relapse. Relapsed AML patients showed higher renin gene expression levels compared to those detected at complete remission and at diagnosis (P=0.000–0.001), respectively. None of our control subjects were positive for renin gene expression. At diagnosis, AML patients with haemoglobin less than 10 g/dl showed higher renin levels compared to those with haemoglobin of at least 10 g/dl. We used median renin gene expression levels to divide AML patients into high and low groups at diagnosis. At diagnosis, the group with higher renin expression showed higher total leukocyte count (TLC) than did the group with lower renin expression. At relapse, the higher renin expression group showed a higher peripheral blood (PB) blast percentage than did the lower renin expression group. Conclusion Renin expression can predict outcomes in AML patients and could be used as a therapeutic target.
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Pretransplant C-reactive protein, ferritin, albumin, and platelet count as prognostic biomarkers of hematopoietic stem cell transplantation outcome in hematological malignancies p. 76
Hoda A Gadallah, Mohamed H Khalaf, Haydi S Mohamed
DOI:10.4103/ejh.ejh_47_17  
Aim To study the prediction of prognosis after hematopoietic stem cell transplantation (HSCT) by clinically available biomarkers prior to transplantation (CRP, Ferritin, albumin and platelet count). Background Previous studies have shown that a number of objective laboratory “biomarkers” are of interest in pre-HSCT risk-assessment: Serum albumin inversely correlates with age, smoking, obesity and hypertension, and predicts cardiovascular mortality. Serum ferritin is an acute phase reactant, and elevated levels suggest iron overload, which has been linked to post-HSCT infections. Finally low platelet count, could indicate poor marrow function related to persistent malignancy or effects of prior treatment. Methods The study included patients admitted at the Bone marrow transplantation Units in Egypt (Ain Shams University Hospitals and Maadi Armed Forces Medical Compound and Sheikh Zayed Specialized Hospital) between August 2015 and December 2016. The study population consisted of 30 adults aged from 18 to 60 years; 26 patients were subjected to autologous-HSCT to treat high-risk or relapsing NHL, MM, relapsing HL, and 4 patients subjected to allogeneic-HSCT to treat 1st complete remissiom (CR) AML, 2nd CR AML. The biomarkers included pre-transplant serum albumin, platelet count, C-reactive protein (CRP) and serum ferritin were centrally quantified by (ELISA) technique. All patients were followed up till day +90 post transplant. Results Shock developed post-transplant in patients with CRP ˃10 mg/L (P=0.026) while non-relapse mortality was associated with the pre-specified thresholds of platelet count <150,000/μl (P=0.046) but not CRP ˃10 mg/L (P=0.1) and s.albumin <3.5 g/dL (P=0.3) and s.ferritin <2500 ng/mL. (P=0.9). Three months overall survival (OS) was 87% among the studied group. Mean survival time was associated with low platelet count <150,000/μl (P=0.024) not with CRP ˃10 mg/L (P=0.1) and s.albumin <3.5 g/dL (P=0.6) and s.ferritin <2500 ng/mL (P=0.9). Conclusion We conclude that elevated level of pre-transplant CRP, s.ferritin associated with high NRM without statistically significant difference while NRM was higher in patients with normal s.albumin pre-transplant without statistically significant difference, low platelet count <150,000/μl associated with increased NRM with statistically significant difference (P=0.046), and lower survival the 3 months overall survival (OS) among patients was about 87%. Mean survival time was statistically significant in patients with low platelet count (P=0.024) not in CRP, ferritin and albumin.
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Correlation between splenic size and CD4+ T lymphocytes in sickle cell anaemia patients in a Tertiary Hospital p. 85
Omotola T Ojo, Ajayi A Ibijola, Wuraola A Shokunbi, Olusogo E Busari, Philip O Olatunji, Arinola Ganiyu
DOI:10.4103/ejh.ejh_15_17  
Background Impaired leucocyte function, loss of both humoral and cell-mediated immunity and splenic dysfunction are partly responsible for increased susceptibility to infection in patients with sickle cell anaemia (SCA) with resultant increased morbidity and mortality. Objective This study was carried out to determine the correlation between splenic size and CD4 T lymphocytes, which are two of the parameters highly involved in immunological status of an individual, among patients with SCA. Materials and methods A comparative cross-sectional study of 40 SCA patients in steady state and 40 age-matched and sex-matched healthy Haemoglobin A controls was carried out. The blood samples were analysed for CD4+ T lymphocytes by flow cytometry, whereas spleen size was determined by ultrasonography. Data were analysed using statistical package for the social sciences version 17, and level of significance was put at P less than 0.05. Result There was a negative correlation (r=−0.150) between CD4 T lymphocyte count and splenic size in sickle cell haemoglobin; however, the relationship is weak, and also not statistically significant (P=0.36). Conclusion The importance of the spleen in immunity has been widely proven with consequent increased susceptibility to infection following the absence of spleen or splenic dysfunction. This study shows that CD4 T lymphocyte count may not be of prognostic value in the course of the disease. However, functionality of CD4 T lymphocytes vis-à-vis cytokine expression in relation to spleen size and function should be studied in patients with SCA.
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Relevance of CD49d and CD38 expressions as predictors of disease progression in chronic lymphocytic leukemia p. 88
Amany H Abdelrahman, Mona H Ibrahim, Mahmoud T Hamza, Ola M Eid, Eman M Hassan, Solaf A Kamel, Maha M Eid, Rasha Y Shahin, Mohamed T Sallam
DOI:10.4103/ejh.ejh_51_17  
Background Chronic lymphocytic leukemia is a heterogeneous disease characterized by a highly variable clinical course. The majority of cases do not require therapy and show identical survival rate with their chronic lymphocytic leukemia-free counterparts of the same age. However, other patients may suffer from an aggressive course of the disease with early need for therapy and shorter overall survival. Objective The aim of this study was to investigate the expression pattern and prognostic value of the adhesion molecules, CD49d and CD38, in chronic lymphocytic leukemia (CLL) patients. Moreover, we attempted to investigate their correlation with trisomy 12, which could help in the clarification of the distinctive clinical features of the trisomy 12+ CLL subset. Patients and methods Seventy newly diagnosed chronic lymphocytic leukemia patients and 50 age-matched and sex-matched controls were included in this study. Patients were subjected to full history taking, clinical examination and abdominal ultrasonography. Laboratory investigations included complete blood count, cytogenetic analysis for the presence of trisomy 12, and flow cytometric assessment. Results A significant positive correlation was detected between CD49d expression and CD38 expression. CD49d showed positive correlation with poor prognostic parameters that included organomegaly, high count of white blood cells, lymphocyte count and trisomy 12. CD38 showed a significant positive correlation with high white blood cell count, lymphocyte count, and splenomegaly. In addition, trisomy 12+ chronic lymphocytic leukemia patients showed significant higher lymphocyte count and splenomegaly. Conclusion Our data confirm the suggested role of CD38 and CD49d as predictors for poor clinical outcome of CLL patients. Moreover, trisomy 12+ CLL cells exhibit a high CD49d expression that may account for the unique clinical characteristics of this group.
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CASE REPORT Top

Successful treatment with bortezomib and dexamethasone combination in a patient with monoclonal gammopathy of renal significance p. 94
Figen Atalay
DOI:10.4103/ejh.ejh_54_17  
A 40-year-old woman was reported to the nephrology outpatient clinic because of sudden-onset hypertensive attack, massive proteinuria, and high levels of creatinine. She had no previous medical history. Membranoproliferative glomerulonephritis and monoclonal κ light chain staining was seen on renal biopsy. She was evaluated for plasma cell diseases in hematology clinic. She was diagnosed as having monoclonal gammopathy of renal significance. Six courses of bortezomib plus dexamethasone were given to her. After this treatment schedule, her renal dysfunction and hypertension were resolved. Monoclonal gammopathy of renal significance is a disease caused by monoclonal immunoglobulins secreted by clonal B cells. Monoclonal gammopathy of renal significance should be considered with any unexplained renal impairment or proteinuria. Hematology department must be consulted as well. If treatment is delayed, permanent kidney damage can occur.
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