Introduction Thalassemias are a group of inherited blood-born disorders caused by abnormalities in the synthesis of hemoglobin chain (α or β chain). β-Thalassemia major is the severest form where individuals usually experience severe transfusion-dependent anemia within their first two years of life; thus, it requires regular transfusions of packed red blood cell (RBC) and desferrioxamine injections. Patients with thalassemia have ineffective erythropoiesis and faster RBC turnover owing to the short life span of RBCs and so increased body demand of energy and nutrients to keep normal erythropoiesis. Trace elements and minerals have a vital role in the appropriate functioning of the body. Aim of the study The aim of this study is evaluation of zinc, copper, and magnesium levels in patients having β-thalassemia major and establish if these patients need copper, zinc, and magnesium supplementation or no. Patients and methods In this study, we included 35 patients diagnosed as having β-thalassemia major attending pediatric hematological unit at Sohag University Hospital within a period of 6 months from January 2018 to June 2018. We studied the serum level of various trace elements in children with β-thalassemia major of both sexes aged below 18 years in a cross-sectional study by assessment of serum level of zinc, copper, and magnesium using classical colorimetric end-point technique by a semiautomated, programmable photometer 5010. Results Only 6.7% of the studied patients had serum zinc levels of less than 66 µg/dl and 13.3% had copper levels of less than 63.7 µg/dl, whereas more than one-third of the participants had copper levels higher than 140.12 µg/dl. Serum magnesium levels of all the studied patients were within the normal range (1.46–2.68 µg/dl). Conclusion Empirical zinc, copper, and magnesium supplementation should not be regularly recommended in patients with β-thalassemia major.

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Background Iron deficiency is a worldwide health problem that can cause long term consequences. Hepatic hormone hepcidin regulates systemic iron homeostasis. Urinary hepcidin level could be an effective tool in assessment of iron status. Aim The present study aims to evaluate the diagnostic role of urinary hepcidin to predict different stages of iron deficiency (ID) in children. Methods We studied 75 children with iron deficiency and 25 healthy control children. The diagnostic performance of urinary hepcidin was estimated by analyzing the receiver operating characteristic curve. Diagnostic cut-off point with a high predictive value for iron deficiency were selected. Results Urinary hepcidin levels were significantly lower in all stages of iron deficiency than in the control group. Significant positive correlations between urinary hepcidin level with hemoglobin, mean corpuscular volume, serum iron, ferritin and Tsat had been confirmed. Hepcidin cutoff values of ≤ 369 ng/ml in ID stage -1 , 315 ng/ml ≤ in ID stage-2 and 293 ng/ml in ID stage-3 were associated with a high diagnostic likelihood for iron deficiency. Conclusion We found that in all stages of ID, hepcidin levels were significantly lower than the control group. Urinary hepcidin assay provides a reliable non-invasive screening mean of diagnosing ID state in children.

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Background Hodgkin’s lymphoma (HL) is a B-cell lymphoproliferative tumor that has an excellent prognosis in most patients using chemotherapeutic protocols, with or without radiation. Some populations including aged people and adolescents and young adults did not gain similar benefits from treatment advances when compared with pediatric and other adult patients. Vitamin D deficiency was suggested as a risk factor for many malignant tumors, and its supplementation may have a role in management of some cancers. Aim This study aimed to evaluate vitamin D levels in patients with HL at presentation and after 12 weeks of supplementation in relation to treatment outcome. Patients and methods A total of 24 treatment-naive patients with pathologically confirmed HL were consecutively recruited. Vitamin D levels were assessed at presentation and after 12 weeks of vitamin D supplementation using automated electrochemiluminescence binding assay. All patients received ABVD protocol as a first-line therapy. The outcome of patients after the six cycles was classified as complete response, partial response, stable disease, or relapsed/progressive disease. Results Female patients and those with B symptoms had significantly lower vitamin D levels (P=0.032 and 0.045, respectively). Patients who failed to respond to ABVD had significantly lower vitamin D levels compared with that of responders (P=0.022). Vitamin D levels did not affect progression-free survival (log-rank test P=0.69). Conclusion Lower vitamin D level was associated with nonresponsiveness to ABVD regimen. Vitamin D supplementation in patients with HL did not alter the progression-free survival of the studied patients. However, these findings await more validation through recruiting larger cohorts of patients for longer follow-up periods.

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Background Early diagnosis of sepsis is vital for neutropenic patients with hematologic malignancies. However, finding an early marker is still a challenge. Aim The aim of this study was to assess the utility of midregional fragment of proadrenomedullin (MR-proADM), compared with C-reactive protein (CRP), as an early marker for sepsis in severely neutropenic young patients with hematologic malignancies. Patients and methods A total of 100 severely neutropenic patients with hematologic malignancies, 1–15 years old, admitted to the Pediatric Hematology and Oncology Unit (Zagazig University, Zagazig, Egypt), and developed fever, were randomly recruited. Blood samples, taken on the first day of each febrile episode, were cultured. In addition, on the first and second febrile days, serum CRP and serum MR-proADM levels were estimated. Results Patients constituted two groups: a bacteremia/sepsis (BS) group of 36 patients with 47 febrile episodes, and pyrexia of unknown origin (PUO) group of 64 patients with 88 febrile episodes. CRP levels were not statistically different between the BS and PUO groups on either days 1 or 2. However, MR-proADM levels were significantly different between the two groups on both days. On receiver operating characteristic curve analysis, CRP was a poor differentiator between BS and PUO. Area under the receiver operating characteristic curve for CRP on days 1 and 2, were 0.509 and 0.529, respectively, whereas MR-proADM had higher discriminatory power from day 1 (area under the curve=0.939). Conclusion This study adds to the recently increasing literature indicating that MR-proADM is a promising early marker for sepsis in severely neutropenic young patients with hematologic malignancies.

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Introduction Iron overload is a common complication in patients with β-thalassemia major (β-TM) and is defined as serum ferritin level higher than 1000 ng/ml. Deposition of iron in body organs, mainly in the liver, leads to hepatocytes damage. Keratins are the major epithelial-specific subgroup of intermediate filament proteins. Increased apoptosis and/or necrosis play a role in the pathogenesis and determination of disease progression. Keratin 18 is cleaved by caspases during apoptosis and creates M30 fragments. Soluble intact K18 (M65) is also released from cells during cell death. Patients and methods A prospective case–control study of 70 multitransfused patients with β-TM and 22 controls was conducted in Paediatric Haematology Unit of Assiut University hospital from January 2016 till April 2017. The study participants were screened for liver enzymes, hepatitis markers (hepatitis C virus antibodies and hepatitis B virus antigen), and serum ferritin levels. Circulating levels of human keratin 18-M65 (K18-M65) were measured by enzyme-linked immunosorbent assay. Results Serum M65 levels were higher in patients’ group compared with healthy controls (P<0.001). M65 serum levels were also positively correlated with the serum levels of liver transaminases including aspartate aminotransferase (AST) (δ-0.470, P<0.001) and alkaline phosphatase (δ=0.180, P=0.043), and serum ferritin (δ=0.450, P=0.043). Conclusion M65 serum levels increased significantly with increased levels of serum ferritin and liver enzymes (aspartate aminotransferase and alkaline phosphatase) between β-TM patient groups.

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Background The mutations and polymorphisms of the X-ray repair cross-complementing group 1 (XRCC1) gene may render base excision repair pathway ineffective, leading to cancers including leukemias. The variable occurrence of XRCC1 Arg399Gln polymorphism affects diverse ethnic groups differently; however, there is a lack of data for the Saudi population. This study sought to elucidate the allelic distribution and the frequency of XRCC1 Arg399Gln polymorphism in Saudi Arabian population and also to compare the same with other populations globally. Materials and methods PubMed (Medline) and other relevant web-databases were used to extract published epidemiological studies conducted in diverse racial/ethnic groups. Results The frequency of XRCC1 Arg399Gln variant allele (A) was found to be 25%. A significant difference was found for the UK (P<0.0001), Turkey (P≤0.001), Austria (P=0.009), Ukraine (P=0.008), Poland (P≤0.001), India (P≤0.001), and Romania (P=0.015) population, upon comparison of this frequency with that of other populations. Conclusion The findings of this study show a unique pattern of DNA repair gene XRCC1 Arg399Gln variant allele in Saudi Arabia population possibly because of ethnic variation. The results may help in risk evaluation of individuals having exposure to environmental carcinogens and an eventual leukemia susceptibility in diverse populations.

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Background Anemia is one of the most common blood disorders globally, affecting one-third of the world’s population, caused due to lack of iron in the human blood resulting in an abnormal hemoglobin range. Lung disorders are the third leading life-threatening disease worldwide, which is caused due to inflammation or injuries in the lungs or respiratory tract. Altitude increase is suspected to play a role in the induction and progression of both anemia and lung disorders. A point mutation SERPINA1 gene, a serine protease inhibitor, is directly linked with lung damage, has also been found to cause the anemic condition. Materials and methods The present study is aimed at analysis of variations of the biochemical parameters in both the diseases along with the altitudinal comparison, in order to predict the influence of altitude on them. The study was also aimed at depicting the association of anemia with lung disorders and hence SERPINA1 gene was examined for mutation to determine the risk for lung disorders. Results The biochemical and altitudinal comparison gave significant association, whereas, negative results were obtained in the genetic analysis. Conclusion All the obtained results clearly indicate that altitude has a major role in influencing the incidence and prevalence of anemia. It has also been found that all the anemic patients are not susceptible to lung disorders on a genetic basis.

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Objectives Acute myeloid leukaemia 1-eight twenty-one (AML1-ETO) is the most frequent abnormality seen in ∼40% of patients with acute myeloid leukaemia with French-American-British-M2 morphology and has received much attention over the past decade. We performed this study to investigate the prevalence and clinical significance of AML1-ETO in a cohort in Assam, India. Coprevalence and clinical significance of FMS-like tyrosine kinase 3, nucleophosmin 1 (NPM1), and p53 mutations, expression of epidermal growth factor receptor (EGFR), and flow markers were also documented and co-related with disease progress. Materials and methods Peripheral blood/bone marrow aspirates were collected from 165 de novo acute myeloid leukaemia patients. Reverse transcriptase PCR and real-time PCR assays were used for detection. Statistical analyses were carried out using statistical packages SPSS 22.0 and Epi Info 2000. Results AML1-ETO t(8;21)(q22;q22) were detected in 24 of 165 (14.60%, 95% confidence interval: 9.77–20.56) samples. The morphologic finding of bone marrow in AML1-ETO-positive patients revealed a higher occurrence of Auer rods. Prominent golgi and abnormal granules were abundantly found with an increasing number of large blasts. The prevalence of NPM1, p53 and EGFR were detected in 7/24 (29.50%), 2/24 (10.50%), and 4/24 (17%) patients, respectively. There was no significant difference in the overall survival (P=0.68) between AML1-ETO-positive and AML1-ETO-negative patients. White blood cell (WBC) count (P=0.00), platelet count (P=0.00), haemoglobin level (P=0.03) and blast count (P=0.01) showed a significant difference between AML1-ETO alive and dead patients. NPM1 mutation was associated with a high WBC count. Association of EGFR and NPM1 in AML-ETO-positive patients was not significant (P=0.75 and 0.88, respectively) compared with AML1-ETO-negative patients. Conclusion In this cohort study, the remission rate of AML1-ETO t(8;21) was not as high as compared with western countries. The presence of NPM1 mutants in AML1-ETO patents is a striking observation, but NPM1 and EGFR had no significant impact on AML1-ETO patients.

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Background The role of cytokines in inhibitor-positive versus inhibitor-negative patients with hemophilia A (PWHA) is controversial. Raised levels of B cell activating factor (BAFF) and B cell maturation antigen (BCMA) have been recently reported and have been linked to presence of inhibitors. Aim To directly quantify serum BAFF and BCMA along with interleukin (IL)-10, IL-5, and tumor necrosis factor-α (TNF-α) in PWHA following an on-demand schedule for factor VIII replacement, and to correlate these with demographic, clinicopathological, and treatment parameters. Patients and methods The study group included 35 inhibitor-positive, 131 inhibitor-negative PWHA, and 20 healthy controls. Serum levels of BAFF, BCMA, IL-10, IL-5, and TNF-α were determined by enzyme-linked immunosorbent assay. Results The mean serum levels in inhibitor positive, inhibitor negative, and healthy controls for BAFF was 0.346, 0.218, and 0.118 pg/ml (P=0.280), for BCMA was 0.266, 0.176, and 0.187 pg/ml (P=0.298), for IL-10 was 13.71, 5.72, and 2.45 pg/ml (P≤0.001), for IL-5 was 2.90, 2.74, and 2.50 pg/ml (P=0.205) and for TNF-α was 5.20, 6.78, and 4.0 pg/ml (P=0.558), respectively. Six (30%) inhibitor-positive PWHA had elevated BCMA levels while none of the inhibitor-negative PWHA showed increased values. Conclusion The current study has, for the first time, analyzed BAFF and BCMA in PWHA with inhibitor status in a clinical setting of on-demand therapy. As a preliminary conclusion we feel that, while cytokines play a role in pathogenesis they do not seem to trigger inhibitor development in PWHA.

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Background Progranulin (PGRN) plays a substantial role in tumorigenesis, and its serum level is increased in many types of human cancers. Moreover, B7-H4 plays a remarkable role in regulation of the tumor microenvironment. It is overexpressed in different types of human cancers, and dysregulation of its expression has been associated with tumor progression. Aim This study aimed to estimate serum levels of PGRN and B7-H4 in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) and their relation to patient prognosis and survival. Patients and methods This case–control study was performed on 50 patients with newly diagnosed DLBCL and 30 apparently healthy individuals as a control group. Enzyme-linked immunosorbent assay was used to measure serum levels of PGRN and B7-H4. Results This study revealed that serum levels of PGRN and B7-H4 were higher in patients with DLBCL compared with the control group. Receiver operating curve analysis showed that serum PGRN at a cutoff value of greater than 98 ng/ml had a sensitivity of 80% and a specificity of 93.33%, and serum B7-H4 at a cutoff value of greater than 49 ng/ml had a sensitivity of 70% and a specificity of 96.67% for DLBCL diagnosis. In patients with DLBCL, progression-free survival and overall survival significantly decreased with increased serum levels of PGRN and B7-H4 above the cutoff levels. Conclusion PGRN and B7-H4 can be useful in determining prognosis of patients with DLBCL.

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Background The diagnosis of chronic myeloid leukemia (CML) is complex based mainly on the presence of Philadelphia chromosome with morphological characteristics and leukocyte alkaline phosphatase (LAP) score. However, it can be confused and should be differentiated from different disorders including specifically the leukemoid reaction (LR). HOX transcript antisense RNA (HOTAIR) expression may be a useful biomarker for detection of cancer. Objective This study was aimed to explore the accuracy of HOTAIR as a diagnostic marker for CML. Patients and methods During the period from 1 February 2017 till 31 December 2018, patients with CML and LR were enrolled in this study. The LAP score was assessed for all patients by cytochemistry on their peripheral blood smear. HOTAIR expression was relatively quantified using the RT-qPCR technique. The diagnostic accuracy of serum HOTAIR expression in differentiating both groups was evaluated. Results A total of 66 patients were included and assigned into two groups; CML patients (group I) and LR patients (group II). The serum HOTAIR expression level was significantly higher in the CML group than the LR group (P<0.001). The area under curve (AUC) of the serum HOTAIR was detected as 0.883 with a sensitivity of 67.7% and a specificity of 85.7% at a cutoff more than 2.8 for CML diagnosis which is slightly higher than that for the LAP score (AUC difference=0.0369; P=0.334). The increased serum HOTAIR expression is independently related with poor clinical, laboratory features of CML and the decreased LAP score. The diagnostic accuracy of HOTAIR was detected to be increased if combined with the LAP score (AUC=0.900). Conclusion Our study findings suggested that the serum HOTAIR can serve as a potential marker for the CML with high diagnostic accuracy specifically if combined with the LAP score.

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Background Reduced-intensity conditioning for allogeneic stem cell transplantation (allo-SCT) is possible for patients with myelodysplasia syndrome (MDS) who are ineligible for high-dose myeloablative conditioning allo-SCT. Objective To determine the outcome of reduced-intensity allo-SCT in Egyptian patients with MDS. Patients and methods A total of 18 patients with MDS were included, and the median age was 39 years. The conditioning regimen consisted of fludarabine (150 mg/m²) and busulfan (8 mg/kg). All patients received mobilized peripheral blood stem cells. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and methotrexate. Results The Kaplan–Meier-estimated 2-year overall survival and disease-free survival were 49 and 33%, respectively. The Kaplan–Meier-estimated probability of relapse at 2 years was 43.5%. The Kaplan–Meier-estimated probability of nonrelapse mortality at 2 years was 43%, and severe acute GVHD and sepsis were the main causes of death. The Kaplan–Meier-estimated probabilities of acute and chronic GVHD were 31 and 20%, respectively. Conclusion Although reduced-intensity conditioning regimens allowed for decreased transplant-related toxicities and increased durable engraftments, their use was associated with a high incidence of relapse in patients with MDS.

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