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   2012| October  | Volume 37 | Issue 4  
    Online since June 21, 2014

 
 
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ORIGINAL ARTICLES
Lipid profile in children with β-thalassemia major
Samera Z. Sayed, Sheren E. Maher, Ghada Adel, Lamea Hamdy
October 2012, 37(4):183-186
DOI:10.7123/01.EJH.0000418696.53110.08   
Background

β-Thalassemia major is a very serious blood condition, as affected patients are unable to synthesize enough healthy red blood cells and depend on blood transfusions throughout their life.

Aim of work

The aim of the study was to evaluate the lipid profile in patients with β-thalassemia major.

Patients and methods

Fifty patients with β-thalassemia major and 25 healthy controls were included in this study. They were subjected to complete history taking, a thorough clinical examination, and laboratory investigations including complete blood count, liver function test, and assessment of serum ferritin levels and fasting lipid profile including total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides (TGs) levels.

Results

Patients with β-thalassemia major showed significantly lower total cholesterol, HDL-cholesterol, and LDL-cholesterol when compared with controls. Serum TG levels of β-thalassemia major patients were found to be significantly higher than the levels in control individuals. Our results revealed that the lipid profile changed in patients with thalassemia major.

Conclusion

In thalassemic patients, adequate chelation therapy with normalization of serum ferritin level and monitoring of TGs is highly recommended, and they are treated aggressively if the levels are increased. Several interventions including antioxidant therapy and vitamin-lowering and lipid-lowering agents should be used in high-risk patients with β-thalassemia major to decrease the risk of atherosclerosis.

  1,644 3,478 -
Prognostic significance of serum monoclonal immunoglobulin in B-chronic lymphocytic leukemia
Mona A. El-Hussiny, Lamiaa Ibrahim, Emad Azmy, Sameh Shamaa
October 2012, 37(4):240-245
DOI:10.7123/01.EJH.0000419280.71909.65   
Background

Serum immunoglobulin (Ig) paraprotein can be detected in a subset of patients with chronic lymphocytic leukemia (CLL) by serum protein electrophoresis and immunofixation electrophoresis. CLL with Ig paraproteinemia had an inferior survival compared with patients with CLL without serum paraprotein.

Participants and methods

The present study was carried out on 100 patients with B-CLL (60 men and 40 women) ranging in age from 33 to 75 years. The staging of CLL was performed according to the Binet staging system. Venous blood samples were obtained from B-CLL patients for a complete blood count. Serum was separated for the measurement of lactate dehydrogenase (LDH), β2-microglobulin (β2-MG) levels by ELISA, and Ig paraprotein. Bone marrow aspiration was carried out for all B-CLL cases. Prognostic markers of CD38 and &zgr;-chain-associated protein kinase-70 (ZAP-70) expression were also analyzed.

Results

Twenty-two patients had Ig paraproteinemia of a total of 100 untreated patients with CLL, frequency 22%. There was a highly significant elevation in LDH, β2-MG, CD38, ZAP-70, IgG, and IgM in CLL with monoclonal paraprotein versus CLL without monoclonal paraprotein. There were positive correlations of serum IgG paraprotein and serum IgM paraprotein with advanced Binet stage (P<0.00 and P=0.00), high level of β2-MG (P=0.00 and 0.00) and LDH (P=0.00 and 0.00), CD38 positivity (P=0.00 and 0.02), and ZAP-70 positivity (P=0.00 and 0.01). Also, there was a positive correlation between high serum β2-MG concentration with Binet stage (P=0.00), high level of LDH (P=0.00), CD38 positivity (P=0.00), and ZAP-70 positivity (P=0.02). After a follow-up of 60 months, 15 patients (15%) died. Eight (36.3%) patients with Ig paraproteinemia died during the observation period, whereas among the 78 patients without Ig paraproteinemia, seven (8.9%) died.

Conclusion

β2-MG and Ig paraprotein serve as poor prognostic markers for B-CLL. Patients with CLL with serum Ig paraprotein represent a heterogeneous group with an inferior clinical outcome. Serum Ig paraprotein might be applied for the assessment of prognosis in patients with CLL.

  2,130 178 -
Role of adiponectin in chronic lymphocytic leukemia
Hosneia K. Akl, Tarek M. Elgohary
October 2012, 37(4):187-192
DOI:10.7123/01.EJH.0000418697.30240.35   
Background

Assessing for clinical stage and searching for various new prognostic markers can be useful in better understanding chronic lymphocytic leukemia (CLL) pathogenesis and in deciding when to initiate therapy and how this therapy can be effective. Adiponectin is an abundant circulating adipokine that exhibits beneficial effects in the vasculature and has anti-inflammatory, antiproliferative, and proapoptotic properties.

Aim of the study

The aim of this study was to investigate the role of adiponectin in CLL pathogenesis and its relation to the well-established CLL prognostic factors.

Participants and methods

Forty-five individuals divided into two groups were included. Group I comprised 35 patients classified into three subgroups (Ia: the low-risk group; Ib: the intermediate-risk group; and Ic: the high-risk group). Group II comprised 10 apparently healthy age and sex-matched controls. In addition to routine laboratory investigations, β2-microglobulin (β2-MG) and adiponectin and angiogenin (ANG) were measured by immunoturbidimetry and ELISA techniques, respectively. ZAP-70 and CD38 expressions were assessed by flow cytometry.

Results

Adiponectin was significantly lower in patients than in controls. It was significantly lower in subgroup Ic than in subgroup Ia (P<0.01), whereas the P-value was nonsignificant when Ib was compared with Ia and Ic. ANG was significantly higher in patients than in controls (P<0.001) and its level increased with clinical stage (Ia<Ib<Ic) with P-value less than 0.0001. Regarding β2-MG, it was higher in patients than in controls and the Ic subgroup had a significantly higher level compared with Ia and Ib subgroups (P<0.001) with no significant difference between these two subgroups. ZAP-70 expression was positive in 45.7% of the patients who had significantly lower adiponectin levels than those who were ZAP-70 expression negative (P<0.01). Forty percent of the patients were positive for CD38 expression with significantly lower adiponectin levels compared with CD38-negative patients (P<0.01). Adiponectin was inversely correlated to ANG, β2-MG, and percentages of ZAP-70-expressing and CD38-expressing cells.

Conclusion

These results support a key role for adiponectin in CLL, suggesting a possible promising therapeutic potential.

  771 1,286 -
Therapeutic decision analysis for monitoring UFH therapy using activated partial thromboplastin time compared with anti-Xa assay
Zinab Mourad, Wafaa El-Neanaey, Wael Shaalan, Mohamed A. Faghry
October 2012, 37(4):287-290
DOI:10.7123/01.EJH.0000419288.92101.39   
Aim

At present, the traditional activated partial thromboplastin time (a-PTT) of 1.5–2.5 times the control value for monitoring unfractionated heparin (UFH) therapy continues to be used in the coagulation laboratory of Alexandria Main University Hospital. This study was conducted for the following reasons: to evaluate the relationship between heparin concentration and a-PTT results using Sysmex CA-1500; to define thea-PTT therapeutic range for our system; and to assess the level of agreement between a-PTT results and those obtained using the anti-Xa assay for monitoring UFH therapy.

Results

A significant positive correlation between a-PTT and anti-Xa assay results was noted (P=0.907, r=0.000, and P=0.098, r=0.000, for therapeutic a-PTT and therapeutic ratio, respectively). Regression analysis was carried out to determine the anti-Xa-derived therapeutic range (a-PTT results that correspond to a plasma heparin concentration of 0.3–0.7 U/ml by anti-Xa assay). The a-PTT therapeutic range was 64.4–107.93 s; the therapeutic range for the a-PTT ratio was 2.13–3.56 and that for the1.5–2.5 control method was 45.27–75.75 s. The agreement between the the a-PTT therapeutic range and the results of the anti-Xa assay was 78%, whereas the agreement between the 1.5–2.5 control method and the anti-Xa assay was 0.097%. Moreover, the potential for over therapeutic levels occurs more frequently with the 1.5–2.5 control method.

Conclusion

Anti-FXa-derived therapeutic range on Sysmex CA-1500 is superior to that obtained using the 1.5–2.5 control method in clinical decision making. Therapeutic ranges for various a-PTT reagent–coagulometer combinations could be provided by reagent manufacturers or central reference laboratories to the institutions that are not equipped to measure anti-Xa or to those for which the access to plasma samples from treated patients is limited.

  1,781 130 -
CD64 ( diagnostic accuracy compared with the hematologic scoring system and CRP in neonatal sepsis)
Hanan E. Mohamed, Hosneia K. Akl, Ehab A. El Banna
October 2012, 37(4):193-199
DOI:10.7123/01.EJH.0000418698.37863.30   
Background

Despite the advances in prenatal and neonatal care, there is still a high incidence of neonatal sepsis and new accurate and rapid tests are required that facilitate the identification of this condition in order to initiate an early effective treatment for a successful outcome.

Objective

To evaluate the diagnostic performance of CD64 expression in relation to the hematologic scoring system (HSS) and C-reactive protein (CRP) either individually or in combination in neonatal sepsis.

Participants and methods

This study included 36 neonates, 13 with culture proven sepsis (group I), 13 with clinically suspected sepsis and culture-negative results (group II), and 10 age-matched and sex-matched healthy neonates (control group). All neonates were examined thoroughly. Complete blood counts were performed, from which HSS was formulated and CRP was measured. Bacterial blood cultures (urine and cerebrospinal fluid when indicated) were carried out only for patients. Neutrophil surface expression of CD64 was assessed by flow cytometry.

Results

Neutrophil CD64 expression was significantly higher in neonates with proven sepsis than the other groups (P=0.0001). A significant positive correlation was found between CD64 expression and HSS (r=0.6581, P<0.001) and CRP (r=0.7531, P<0.001). In terms of the validity of CD64 expression compared with HSS and CRP, the accuracy was 86.1% with a specificity and a positive predictive value (PPV) of 82.6 and 75%, respectively; HSS and CRP sensitivities were 92.3 and 100%, respectively, but with lower specificities (73.9 and 52.2%, respectively) and PPVs (66.7 and 54.2%, respectively). Combinations of CD64 with the two parameters showed that the best was that of CD64 and CRP as sensitivity reached 100% with a constant specificity and slightly increased PPV and accuracy (76.5 and 88.9%, respectively).

Conclusion

CD64 expression is significantly related to definite sepsis and correlated to HSS and CRP. It is a reliable diagnostic test to differentiate infected from noninfected neonates.

  1,184 339 -
The percentage of deletion of the B-cell neoplasia-associated gene with multiple splicing ( an indicator for the prognosis of CLL)
Nahela A. Shalaby, Dina A. Fouad, Doaa G. Eissa, Rasha I. Ibrahim
October 2012, 37(4):257-261
DOI:10.7123/01.EJH.0000419283.17651.23   
Background

Deletion of the B-cell neoplasia-associated gene with multiple splicing (BCMS) maps to 13q14 is the most common genetic abnormality in B-chronic lymphocytic leukaemia (B-CLL) patients. Previously, CLL patients with del 13q14.1 were known to have a favourable outcome. However, recent research has shown that increased percentage of cells with del 13q may lead to a poor prognosis or may exert an adverse effect on the biological characteristics of this disease.

Objectives

To assess the influence of the number of malignant cells carrying del 13q14 (BCMS) on the clinical characteristics and prognosis of CLL patients.

Patients and methods

Fluorescence in-situ hybridization technique using a locus-specific identifier 13q14 probe was applied on 76 peripheral blood samples of B-CLL patients, in addition to the routine panel of probes (locus-specific identifier 17p13,11q23 and centromeric 12) together with immunophenotyping using the routine panel for lymphoproliferative disorder.

Results

Deletion of 13q14 was detected in 40/76 (52.6%) patients. Those patients with greater than 84% positive cells for the deletion had a statistically significant association with advanced clinical Rai staging, lymphocyte doubling time less than 12 months, lower Hb level, higher total leucocytic count and lower platelet count. Follow-up of all patients showed that 30/76 (39.5%) patients showed a good therapeutic response; 28/30 (93.4%) of the patients were positive for 13q14 (BCMS) deletion, with a percent of cells ranging from 12 to 67%. The remaining 46/76 (60.5%) patients showed a poor therapeutic response; 12/46 (26.1%) of these patients were 13q14 (BCMS) positive, with a percent of positive cells ranging from 84 to 96%. Deletions in 17p13 were detected in 8/76 (10.5%), trisomy 12 was found in 10/76 (13.1%) and 11q23 rearrangements were found in 12/76 (15.7%) patients.

Conclusion

The prognostic significance of del 13q14 is dependent on the percentage of positive cells for this deletion. A high number of losses in 13q14 are associated with a poor prognosis.

  1,362 97 -
Detection of insulin-like growth factor type I receptor in adulthood acute lymphoblastic leukemia by a real-time polymerase chain reaction
Hebatallah Adel Sedky, Dina Adel Fouad, Deena Mohamed Mohamed Habashy, Nisreen Atef Abdel Ghaffar
October 2012, 37(4):228-233
DOI:10.7123/01.EJH.0000419278.87156.66   
Background

Insulin-like growth factor I receptor (IGF-IR) is currently the focus of intensive research aimed at developing novel antitumor agents. It plays a documented novel role in the regulation of the MDM2/p53/p21 signaling pathway during DNA damage. The IGF system plays a critical role in tumor pathogenesis, progression, protection from apoptosis, and metastasis.

Objectives

To detect the expression of IGF-IR in adult patients with acute lymphoblastic leukemia (ALL) in comparison with healthy controls, and to examine its prognostic impact on patients’ outcome, and its possible association with the known standard prognostic factors for ALL.

Participants and methods

Real-time polymerase chain reaction was applied to assess the expression of IGF-IR in 30 newly diagnosed adult patients with ALL and in 10 age-matched healthy controls.

Results

The cycle threshold of IGF-IR expression in the patient group ranged from 20.21 to 30.18 (24.82±3.38), whereas it ranged from 30.21 to 37.98 (34.74±2.94) in the control group. The IGF-IR expression level in patients was statistically significantly higher (P=0.000) than those of the control group. Statistical analysis of IGF-IR expression in relation to standard prognostic factors and patient outcome showed no significance (P>0.05).

Conclusion

IGF-IR is significantly overexpressed in adult patients with ALL at diagnosis, indicating its possible role in pathogenesis. However, it is not valid as a prognostic marker in ALL. There was no significant association of IGF-IR with patient outcome. Considering its role in leukemogenesis, new therapeutic strategies directed against IGF-IR may be beneficial in arresting malignant cell proliferation and survival and blocking the progression of disease.

  1,386 70 -
Expression of myelomonocytic antigens in Egyptian B-cell chronic lymphocytic leukemia ( impact on prognosis)
Deena M.M. Habashy, Amira F. Barakat
October 2012, 37(4):207-212
DOI:10.7123/01.EJH.0000418700.75981.f7   
Background

B-cell chronic lymphocytic leukemia (CLL) is a clonal malignancy of mature B cells that displays immense clinical heterogeneity. Therefore, there has been considerable interest in identifying prognostic markers that can be used to distinguish those patients who may have an aggressive form of CLL. Clinical staging systems lack the ability to predict disease progression. Numerous cellular and molecular markers with potential prognostic and therapeutic significance have been identified. Among these markers are the myelomonocyte-associated markers whose expression on neoplastic lymphocytes in CLL has been reported to correlate with an unfavorable prognosis.

Aim of the study

We aimed to study the expression of the myelomonocytic markers CD13 and CD11b in Egyptian CLL patients in comparison with a healthy control group and assess their relation to other prognostic factors and patient outcomes. This study also aimed to reveal the association of CD38 and FMC7 with prognosis and disease progression.

Participants and methods

Expressions of CD13 and CD11b were detected by flow cytometry in 30 newly diagnosed CLL cases and 10 healthy individuals. Percentages of CD38-positive and FMC7-positive cells were also measured.

Results

CD13 was expressed in three cases (10%), whereas CD11b was expressed in four cases (13.3%) of CLL. CD38 was expressed in 13 cases (43.3%) and FMC7 in 11 cases (36.6%). None of the individuals in the healthy control group expressed CD13 or CD11b. The expression of CD13 and CD38 was significantly correlated with adverse results of complete blood count (P<0.05). CD11b expression was significantly associated with low platelet count (P=0.04). Expression of all studied markers (CD13, CD11b, CD38, and FMC7) was significantly correlated with the presence of 11q deletion (11qdel) (P=0.004, P<0.001, P=0.001, and P<0.001, respectively), diffuse pattern of bone marrow infiltration (P=0.005, 0.01, P<0.001, and P<0.001, respectively), and poor outcome (P=0.002, 0.01, P<0.001, and P<0.001, respectively). The expression of CD38 was also associated with the expression of CD13 and FMC7 (P=0.02 and P<0.001, respectively) and with the presence of trisomy 12 (P=0.01).

Conclusion

CD13 and CD11b expressions were found to be correlated with the standard adverse prognostic factors in CLL and with shorter survival, which questions their future possible role as prognostic markers in CLL. FMC7 and CD38 expression was also associated with unfavorable prognosis and poor outcome.

  1,319 112 -
Cyclin D1 gene amplification in multiple myeloma and its impact on the disease outcome and drug resistance
Eman M. Sewify, Ola A. Afifi, Eman Mosad, Amen Hamdy Zaki
October 2012, 37(4):268-273
DOI:10.7123/01.EJH.0000419285.02404.20   
Background

Cyclin D1 is involved in the normal regulation of the cell cycle and in neoplasia. Inhibition of cyclin D1 function markedly attenuates the proliferation of fibroblasts of colon, esophageal, lung, and pancreatic cancer. However, the prognostic value of overexpression of the cyclin D1 gene in multiple myeloma (MM) is still a point of debate. This study aims at evaluating the prognostic significance of cyclin D1 gene amplification in MM and whether it is correlated with MDR1 expression as an indicator of chemoresistance.

Patients and methods

Twenty-five patients with MM were studied retrospectively. Cyclin D1 gene amplification was studied in bone marrow biopsies of these patients by fluorescence in-situ hybridization. Immunohistochemical study of the bone marrow biopsies was carried out to detect multidrug resistance (MDR1) gene expression. The correlations between the cyclin D1 gene amplification on the one hand and overall survival and MDR1 expression on the other were studied and analyzed statistically.

Results

Cyclin D1 gene amplification was found in 20% of patients with myeloma and was associated with a higher percentage of plasma cell infiltration of the bone marrow and increase liability for multiple osteolytic lesions. Cyclin D1-positive patients had a significantly lower progression-free and overall survival and higher levels of MDR1 compared with cyclin D1-negative patients. Cyclin D1 levels showed a statistically highly significant positive correlation with MDR1 levels (r: 0.802 and P<0.0001).

Conclusion

We suggest that there is an association between cyclin D1 gene amplification and higher disease severity, unfavorable prognosis, and increased expression of MDR1 in patients with MM.

  1,268 89 -
Nucleophosmin (NPM1-A) and FMS-like tyrosine kinase 3 (FLT3/ITD) mutations in acute myeloid leukaemia with a normal karyotype ( frequency and prognostic significance)
Hosneia K.H. Akl, Heba H Gawish, Fouad M Abou Taleb
October 2012, 37(4):200-206
DOI:10.7123/01.EJH.0000418699.75981.36   
Background

Treatment of acute myeloid leukaemia (AML) with a normal karyotype (NK) has always been a challenge for clinicians. This is because it affects the majority of AML patients and falls into the intermediate-risk group that needs further risk stratifications.

Aim of the study

The current study aimed to verify the importance and significance of analysis of NPM1-A and FLT3/ITD mutations, alone and combined, and their relation to prognostic criteria.

Patients and methods

Thirty-five patients with de-novo AML with a median age of 33 years (19–60) and ten healthy volunteers (the control group) were included. All participants were subjected to clinical examination, routine laboratory investigations and (for patients only) bone marrow examination and cytogenetic analysis by the G-banding technique. Using the genomic PCR (RT and conventional) technique, NPM1 type A and FLT3/ITD mutations were studied in the NK-AML patients and controls. Their impacts were evaluated alone and combined.

Results

After cytogenetic analysis 20/35 (57.1) patients proved to be of NK; their median age was 37.5 (19–60) years. This NK-AML group and control group were examined for NPM1 and FLT3/ITD mutations. None of the controls had either mutation. The NK group was categorized into NPM1+ or NPM1− and FLT3+ or FLT3−. Their frequencies were 40% (8), 60% (12) and 40% (8), 60 (12), respectively. These subgroups were assessed after induction chemotherapy for achievement of complete remission (CR), which was recorded in 62.5% of NPM1-positive patients and 0% of NPM1-negative patients, showing a significant difference with a P value of 0.004, whereas nonsignificant difference between FLT3-positive and FLT3-negative patients was recorded. The NK patients were further subdivided into four genetic subgroups: NPM+/FLT3−, NPM−/FLT3−, NPM+/FLT3+ and NPM−/FLT3+, with frequencies of 15, 45, 25 and 15%, respectively. Sixty per cent of patients who achieved CR were NPM1+/FLT3−. Furthermore, 100% of this subgroup achieved CR, 40% of NPM+/FLT3+ also achieved CR, but none of the NPM−/FLT3− and NPM1−/FLT3+ patients did.

Conclusion

Genotypes defined by the mutational status of NPM1, FLT3 are associated with the outcome of treatment in NK-AML patients.

  1,217 121 -
Assessment of placental growth factor and soluble vascular endothelial growth factor receptor 1 in the prediction of pre-eclampsia
Maha Basuni, Waleed M. Fathy, Wail Gaber
October 2012, 37(4):281-286
DOI:10.7123/01.EJH.0000419287.10028.44   
Background

Pre-eclampsia is a pregnancy-associated disease occurring in 5–8% of pregnancies and is a major cause of maternal and fetal morbidity and mortality. A potentially important process in the pathogenesis of pre-eclampsia is an imbalance between placenta-derived proangiogenic and antiangiogenic proteins. The proangiogenic proteins vascular endothelial growth factor (VEGF) and placental growth factor (PLGF) are involved in the regulation of placental vascular development and maternal endothelial function during pregnancy.

Aim of the study

The aim of this study is to assess the PLGF and soluble vascular endothelial growth factor receptor 1 (sVEGFR-1) in the prediction of pre-eclampsia.

Materials and methods

This study included 88 pregnant women: 68 pregnant women with pre-eclampsia divided into two subgroups (mild and severe pre-eclampsia) and 20 healthy pregnant women matched for age and sex, who served as the control group. Laboratory investigations such as determination of complete blood count, blood urea, serum creatinine, aspartate aminotransferase, alanine transaminase, serum albumin, quantitative determination of total protein in urine, estimation of prothrombin time and concentration, serum PLGF concentration, and serum sVEGFR-1 concentrations were carried out by ELISA. BMI was estimated in this study.

Results

The results showed that serum PLGF was highly significant decreased in women with pre-eclampsia when compared with the control group. There was a highly statistically significant difference between mild and severe cases, where the PLGF decreased with increased severity of pre-eclampsia (P<0.001). Serum sVEGFR-1 was highly significantly increased in women with pre-eclampsia when compared with the control group. There was a highly statistically significant difference between mild and severe cases, where the sVEGFR-1 increased with increased severity of pre-eclampsia (P<0.001). ROC study showed that the best cutoff value for sVEGFR-1 was 2075 pg/ml and the sensitivity was 75%, whereas the specificity was 85%. The cutoff value for PLGF was 151 ng/ml; the sensitivity was 75%, whereas the specificity was 72.1%. There was a highly statistically significant negative correlation between PLGF and sVEGFR-1.

Conclusion

Finally, it is concluded that high concentrations of sVEGFR-1 combined with low concentrations of PLGF may be used to predict the development of pre-eclampsia.

  986 100 -
Polysomy 8 in Egyptian patients with de-novo acute myeloid leukemia
Tahany Ali El Kerdany, Hesham Fayek Kayed, Abeer Attia Saad, Shaymaa Salah El-Dine El-Gaafary, Nevine Nabil Moustafa
October 2012, 37(4):213-220
DOI:10.7123/01.EJH.0000418701.83604.d3   
Background

Tetrasomy, pentasomy, and hexasomy of the entire chromosome 8 (polysomy 8) are relatively rare compared with trisomy 8, which is one of the most common recurring aberrations in myeloid hematologic malignancies. Although polysomy 8 appears to adversely influence outcome, little is known about the prognostic significance of polysomy 8 in patients with acute myeloid leukemia (AML).

Aim of the work

The aim of the present work was to study the numerical aberrations of chromosome 8 in Egyptian patients with AML and to clarify its role as a prognostic marker.

Patients and methods

The present study was carried out on 76 newly diagnosed adult patients with AML. They were attending the Hematology Department of Ain Shams University Hospitals. They were subjected to conventional cytogenetic analysis using G-banding and fluorescence in-situ hybridization using a fluorophore-labeled centromeric probe for chromosome 8.

Results

Metaphase and interphase fluorescence in-situ hybridization for detection of polysomy 8 was successfully performed on 72 samples. Patients were divided into two groups: group A comprised patients associated with polysomy 8 (20 patients; 27.8%) and group B comprised patients without polysomy 8 (52 patients; 72.2%). Group A patients had a statistically significant younger age compared with group B (P=0.04). A statistically significant association was seen between polysomy 8 status and hepatosplenomegaly, fever, and lymph node infiltration (P=0.03, <0.001, and 0.05, respectively) but insignificant difference regarding the presence of skin or central nervous system infiltration (P>0.05). The presence of hepatosplenomegaly, skin infiltration, lymph node infiltration, and French–American–British subtype was shown to have a significant impact on patient outcome (P=0.05, 0.03, 0.01, and 0.04, respectively). Patients with skin infiltration, CD34 expression, HLA-DR expression, high/intermediate cytogenetic risk, and presence of polysomy 8 had significantly shorter overall survival.

Conclusion and recommendations

From the current study we conclude that polysomy 8 occurs in 27.8% of de-novo AML cases; 35% of these cases showed tetrasomy of chromosome 8. Polysomy of chromosome 8 was associated with shortened overall survival. Further studies with a larger number of patients are recommended for proper assessment of polysomy 8, especially tetrasomy 8, among Egyptian patients with AML.

  908 77 -
The reliability of endothelial progenitor cells (CD34+, KDR+, and CD34+/KDR+) in the diagnosis of coronary artery disease and its severity
Eman M. Sewify, Ola Afifi, Mona M. Soliman, Ahmad I. Ziada
October 2012, 37(4):262-267
DOI:10.7123/01.EJH.0000419284.25275.82   
Background

Bone marrow-derived endothelial progenitor cells (EPCs) play an integral role in the regulation and protection of the endothelium, as well as new vessel formation. Changes in EPC number and function during coronary heart disease allow their use as a biomarker. However, so far, there is no suggested definite level at which we can diagnose coronary artery disease (CAD) or determine the severity of the disease.

Aim of the work

To assess the sensitivity, specificity, and accuracy of the circulating EPCs count to diagnose coronary heart disease and to predict the severity of the disease.

Patients and methods

The percentage and count of circulating EPCs (CD34+KDR+, CD34+, and KDR+) were measured by flow cytometry in 52 patients who underwent diagnostic angiography. The correlation between the level of the EPCs on the one hand and the presence or absence of CAD and the Gensini score calculated for each patient on the other was determined.

Results

Thirty-eight patients were found to have CAD and 14 had normal coronaries. For those with CAD, 22 had single-vessel disease and 16 had multiple vessel disease. It was found that EPCs (CD34+KDR+% and count and CD34+%) were significantly lower in patients with CAD compared with those with normal coronaries. CD34+KDR+% had an AUROC of 0.846 to diagnose CAD, with a sensitivity of 45.5%, a specificity of 100%, a positive predictive value (PPV) of 100%, a negative predictive value (NPV) of 64.3%, and an accuracy of 72.75%. CD34+% and count and CD34+KDR+ count were negatively correlated with the Gensini score. CD34+% has an AUROC of 0.802 to diagnose the Gensini score of more than 6, with a sensitivity of 100%, a specificity of 55.2%, a PPV of 69%, an NPV of 100%, and an accuracy of 77.6%.

Conclusion

EPCs decrease in patients with CAD compared with those without CAD. CD34+KDR+% can diagnose CAD with a sensitivity, specificity, PPV, NPV, and accuracy of 45.55, 100, 100, 64.3, and 72.75%. CD34% can help to exclude the presence of severe CAD with a sensitivity, specificity, PPV, NPV, and accuracy of 100, 55.2, 69, 100, and 77.6%, respectively.

  842 106 -
Study of transcription factor CCAAT/enhancer binding protein-α (C/EBPα) in adult patients with acute lymphoblastic leukemia
Inas A. Asfour, Rehab S. Elhagracy, Gihan M. Kamal, Nermeen A. Nabih, Amal A. Abass, Rania A. Radwan
October 2012, 37(4):246-251
DOI:10.7123/01.EJH.0000419281.71909.2c   
Background

Leukemic stem cells have self-renewal property. Identification of genes or signaling pathways involved in self-renewal of leukemic stem cells will promote the development of more effective treatment for acute leukemias.

Objectives

To assess the prognostic significance of the CCAATT/enhancer binding protein-α (C/EBPα) transcription factor in primary adult patients with acute lymphoblastic leukemia (ALL) and its correlation to prognosis and response to therapy.

Participants and methods

Forty adult patients with ALL (23 pre-B ALL, one pro-B ALL, four mature B ALL, and 12 T ALL) were recruited from the Hematology Department, Ain Shams University, compared with 25 age-matched and sex-matched healthy controls. All patients were subjected to a complete blood count, blood chemistry, bone marrow (BM) examination, immunophenotyping, cytogenetics, and assessment of the C/EBPα level using real–time PCR at presentation and at D28 of treatment. Patients were followed over a period of 24 months (1–24 ms).

Results

Compared with controls, patients with ALL at presentation and at follow-up showed a highly significant difference in C/EBPα (P<0.01), whereas there was no significant difference between B ALL and T ALL. Patients who achieved remission showed a significant increase in C/EBPα after treatment. There was no significant correlation between C/EPBα and other prognostic factors in ALL, except with the Philadelphia chromosome; there was a significantly negative correlation at diagnosis and at follow-up.

Conclusion

Deficient C/EBPα among patients with ALL may contribute toward its pathogenesis and remission is associated with a significant increase in the C/EBPα level. C/EBPα is an independent prognostic factor and its measurement helps to predict response and contributes significantly toward better management decisions.

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Expression of matrix metalloproteinase-9 and tissue inhibitor metalloproteinase-1 in childhood acute lymphoblastic leukemia
Mohamed A. Mekawy, Sahar S. Abdel Maksoud, Doaa G. Eissa, Abeer A. Abdelmaksoud, Iman A. Ragab, Mahmoud T. Sallam, Adam A. Yousef
October 2012, 37(4):274-280
DOI:10.7123/01.EJH.0000419286.02404.fb   
Background

Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) regulate the turnover of the extracellular matrix and may modulate the biology of hematopoietic cells. They are key players in many physiological and pathological processes such as development, angiogenesis, connective tissue remodeling, as well as tumor invasion and metastasis.

Objectives

Estimate marrow MMP-9 expression and detect the levels of TIMP-1 in patients with acute lymphoblastic leukemia (ALL) and correlate these results to the clinical characteristics and survival studies of the patients.

Materials and methods

Thirty newly diagnosed patients with childhood ALL and 10 healthy control children were studied using real-time PCR for the measurement of mRNA expression of the MMP-9 gene and using the flow cytometric technique for the detection of intracytoplasmic protein levels of TIMP-1.

Results

MMP-9 expression was significantly lower in patients compared with the control group, whereas TIMP-1 expression showed no significant difference between both the groups. No significant difference was observed between patients with a high MMP-9 expression and low MMP-9 expression in terms of clinical and laboratory data, except for the platelet count, which was higher in patients with a high MMP-9 expression. Besides CD34 expression, TIMP-1 expression was not significantly related to clinical and laboratory data of the patients studied. The median TIMP-1 expression, but not MMP-9, was significantly associated with the initial response to therapy. However, neither MMP-9 nor TIMP-1 expression was significantly associated with the relapse rate, overall survival, or event-free survival.

Conclusion

The clinical importance of MMP-9 and TIMP-1 expression in childhood ALL is still unclear. Further larger studies with a longer follow-up period are recommended to confirm the prognostic value of MMP-9 and TIMP-1 expression in pediatric ALL patients.

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Role of P53 deletion in patients with acute myeloid leukaemia
Mona A. Ismail, Tamer M. Ahmed, Iman Z. Ahmed
October 2012, 37(4):252-256
DOI:10.7123/01.EJH.0000419282.79533.ff   
Background

Loss of the P53 tumour suppressor gene located on the short arm of chromosome 17 (17p13.1) is frequently associated with aggressive disease courses and drug resistance. The prognostic association of P53 deletion has been confirmed for chronic myeloid leukaemia, but not for acute myeloid leukaemia (AML).

Aim of work

The aim of the current study was to investigate the prognostic value of P53 deletion in de-novo patients with AML and to correlate this with known prognostic parameters as well as clinical outcome.

Patients and methods

This study was conducted on 91 patients with de-novo AML meeting WHO criteria for AML. The fluorescence in-situ hybridization technique was applied for detection of P53 deletion at the time of diagnosis. Follow-up studies were carried out to evaluate therapeutic response and clinical outcome.

Results

Loss of P53 was detected in eight out of 91 (8.8%) patients with AML. Among them seven (87.5%) had complex aberrations. A significant difference was detected between P53 deletion positive and negative patients as regards age and total leukocyte count. A highly significant association was detected between P53 deletion and incomplete remission. Interestingly, the coexistence of P53 deletion with old age and high total leukocyte count exhibited a negative impact on the outcome in patients.

Conclusion

P53 deletion can be considered as an indicator of poor therapeutic response in AML patients. Developing new drugs targeting the P53 pathway could be a way to improve treatment of AML.

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Treatment of early-stage Hodgkin’s lymphoma outcome ( Kuwait experience)
Rehab S. ElHagracy, Salem H. AlShemmari, Amany Elbassmy
October 2012, 37(4):234-239
DOI:10.7123/01.EJH.0000419279.94780.52   
Introduction

Treatment of early-stage classical Hodgkin’s lymphoma (HL) is changing targeting remission with reduced intensity.

Aim of the work

This study presents a review of treatment of earlystage I and II HL patients treated with adriamycin, bleomycin, vinblastine, dacarbazine (ABVD) with or without radiotherapy.

Materials and methods

Data were analyzed retrospectively from files of patients treated at the Kuwait cancer center from 2002 to 2010. The study included 105 patients divided as follows: group A, which included 34 patients treated by four cycles of ABVD, and group B, which included 71 patients treated by six cycles of ABVD.

Results

Unfavorable risk cases were 47 versus 77.4% in group A versus B. Radiotherapy was added to ABVD in 57.1% of patients; 35.3% of these patients were from group B. No significant difference in remission or relapse was noted between groups A and B (P=0.04). The 5-year overall survival (OS) for patients was 86%, with no difference between the two groups. Patients with B symptoms had significantly lower 5-year OS (73 vs. 92%; P=0.02). Although the presence of bulky disease and erythrocyte sedimentation rate 50 mm/h or more are associated with lower OS, the difference was not significant (P>0.05). Combined therapy yielded better 5-year OS (90.3%) than chemotherapy alone (80.4%), without significance (P=0.29). No cardiopulmonary toxicities or second malignancies were noted but hypothyroidism was evident after neck radiation. This indicates the good outcome of early-stage HL in general. Some prognostic factors could address treatment policy in terms of the presence of B symptoms, bulky disease, and high erythrocyte sedimentation rate.

Conclusion

Modification of therapy on the basis of novel prognostic factors may be of prospective interest.

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The impact of CLLU1 expression as a prognostic marker in chronic lymphocytic leukemia
Maha Atfy, Tarek El-Gohary
October 2012, 37(4):221-227
DOI:10.7123/01.EJH.0000418702.60734.04   
Background

B-cell chronic lymphocytic leukemia (B-CLL) is a clinically heterogeneous disease; some patients rapidly progress and die within a few years of diagnosis, whereas others have a long life expectancy with minimal or no treatment.

Aim of the study

The aim of this study is to assess the pretreatment levels of CLLU1 in relation to other prognostics markers and to evaluate its impact on the prognosis of CLL patients.

Patients and methods

Seventy-three cases of CLL were characterized for CLLU1 level by a semiquantitative RT-PCR. Univariate analysis and correlations were carried out to test the markers’ ability to identify patients at risk and as prognostic markers in the context of established prognostic factors.

Results

CLLU1 expression was determined in 42/73 (57.5%) of B-CLL patients. There was a highly significant difference in the age and Binet staging in both CLL patients with positive CLLU1 and negative CLLU1 expression (P<0.0001 and P=0.0274, respectively). There was a significant increase in CLLU1 expression in CLL patients with positive CD38 and short lymphocyte doubling time (LDT) (P<0.001 and P<0.0044); this significance was not found with high ZAP-70 and β2 microglobulin (B2M) markers. The relative risk of early death with positive CLLU1 was increased with ZAP-70 and LDT (P=0.0204 and 0.0084) and reduced with CD38 and B2M (P=0.0787 and 0.0750). The poor clinical outcome was associated with positive CLLU1 and ZAP-70 and LDT (P=0.0421 and 0.0084, respectively). B-CLL with positive CLLU1 coexpressed with high B2M and/or CD38 had a slower disease progression (P=0.06 and 0.235, respectively).

Conclusion

CLLU1 expression is an important prognostic marker in B-CLL that could potentially be applied to predict outcome in CLL patients. The CLLU1 may be particularly useful in refining the prognosis of CLL patients.

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