Marwa Zakaria

Renal Presentation in Pediatric Acute Leukemia: Report of 2 Cases

Abstract Renal enlargement at time of diagnosis of acute leukemia is very unusual. We here in report 2 pediatric cases of acute leukemia who had their renal affection as the first presenting symptom with no evidences of blast cells in blood smear and none of classical presentation of acute leukemia. The first case is a 4-year-old girl who presented with pallor and abdominal enlargement. Magnetic resonance imaging showed bilateral symmetrical homogenous enlarged kidneys suggestive of infiltration. Complete blood picture (CBC) revealed white blood count 11 × 109/L, hemoglobin 8.7 g/dL and platelet count 197 × 109/L. Bone marrow aspiration was performed, and diagnosed precursor B-cell ALL was made. The child had an excellent response to modified CCG 1991 standard risk protocol of chemotherapy with sustained remission, but unfortunately relapsed 11 month after the end of therapy. The second child was 13-month old, presented with pallor, vomiting, abdominal enlargement, and oliguria 2 days before admission. Initial CBC showed bicytopenia, elevated blood urea, creatinine, and serum uric acid, while abdominal ultrasonography revealed bilateral renal enlargement. Bone marrow examination was done and showed 92% blast of biphenotypic nature. So, biphynotypic leukemia with bilateral renal enlargement and acute renal failure was subsequently diagnosed. The patients admitted to ICU and received supportive care and prednisolone. Renal function normalized and chemotherapy was started. The child achieved complete remission with marked reduction of kidney size but, unfortunately she died from sepsis in consolidation phase of therapy. This case demonstrates an unusual early renal enlargement in childhood acute leukemia. Renal involvement of acute leukemia should be considered in child presenting with unexplained bilateral renal enlargement with or without renal function abnormalities and bone marrow examination should be included in the workup.

Status of serum magnesium in Egyptian children with type 1 diabetes and its correlation to glycemic control and lipid profile

AbstractDiabetes mellitus has been suggested to be the most common metabolic disorder associated with magnesium deficiency, having 25% to 39% prevalence. This deficit could be associated with the development of late diabetic complications, especially macroangiopathy.We aimed to evaluate the status of serum Mg in children with type 1 diabetes and assess its relation to glycemic control and lipid profile.We included 71 Egyptian children with type 1diabetes having their follow-up at Pediatric Endocrinology outpatient clinic, Zagazig University Hospital and 71 age- and sex-matched control. We measured Serum magnesium, HbA1c, and lipid profile in all study subjects.Diabetic children had significantly lower serum magnesium level compared to control children (1.83 ± .27 mg/dL in diabetic children versus 2.00 ± .16 mg/dL in control children). Taking cut-off level of serum magnesium <1.7 mg/dL for definition of hypomagnesemia, hypomagnesemia was detected in 28.2% of diabetic children compared to 9.9% of control children. In diabetic patients, there was statistically significant difference in HbA1c between hypomagnesemic and normomagnesemic group being higher in the low magnesium group, as it is mean ± SD was 11.93 ± 3.17 mg/dL in group I versus 8.92 ± 0.93 mg/dL in the normomagnesemic group. Serum magnesium was found to be positively correlated with HDL (P < 0.001), and negatively correlated with age, HbA1c, triglycerides, total cholesterol, LDL, and duration of diabetes (P < 0.001).We concluded that total serum magnesium was frequently low in Egyptian children with type 1 diabetes and it is correlated with HbA1c and with lipid profile. Hypomagnesemia was more evident in patients with poor diabetic control and those with higher atherogenic lipid parameters. We suggest that low serum magnesium may be included in pathogenesis of poor glycemic control and abnormal lipid profile in children with type 1 diabetes. We need to perform further studies on giving magnesium supplements in diabetic children with hypomagnesemia to observe the effect of correction of serum magnesium on glycemic control, lipid profile, and the risk of diabetic complications.

First report of acute lymphoblastic leukemia in an Egyptian child with β-thalassemia major.

Abstract β-Thalassemia (β-thal) is the most common hereditary anemia in humans. With improvement of treatment protocols, patients are living longer and new complications have emerged. Few articles have reported the occurrence of malignancies among patients with β-thal in different parts of the world. We herein report the first pediatric patient with β-thal major (β-TM), who developed acute lymphoblastic leukemia in Egypt with analysis of the different theories of pathogenesis.

Presepsin as a diagnostic marker of bacterial infections in febrile neutropenic pediatric patients with hematological malignancies

Febrile neutropenia (FN) is often observed in hematological malignancies (HEM). Presepsin is also known as soluble CD14 subtype; it is a glycoprotein fragment derived from monocytes and macrophages. We aimed to evaluate the significance of presepsin and other biomarkers for diagnosis of bacteremia in children with HEM. Sixty pediatric patients with different HEM (acute lymphoblastic leukemia 36, acute myeloid leukemia 12, non-Hodgkin lymphoma 10, and Hodgkin disease 2). Thirty age and sex-matched healthy children serving as control were enrolled in this study. Estimation of presepsin, procalcitonin (PCT), and C-reactive protein (CRP) during episode of FN in addition to absolute neutrophils count (ANC) and blood culture was performed for all the participants. Presepsin levels were higher in the patients than in control with a higher increments in the positive blood cultures than the sterile cases. Presepsin concentration was significantly higher in bacteremia than clinically proved infection and fever of unknown origin. A statistically significant positive correlation between presepsin and CRP plus PCT levels but negative correlation with ANC were observed in the patients subgroups. Presepsin is a useful marker for detection of bacteremia with sensitivity and specificity (100 and 85.7%). This finding supported that presepsin was superior to PCT and CRP in identifying bacterial infection in FN.

Can CD34/CD123 distinguish between normal and leukemic B-cell precursors?

Background/objective B-cell acute lymphoblastic leukemia (B-ALL) is the most common acute leukemia in children. There are many overlaps between leukemic lymphoblast and hematogones regarding their morphologic and immunophenotypic characteristics. CD123 is one of the markers that can be used to distinguish between leukemic lymphoblast and hematogones. In this study, we aimed to demonstrate the pattern of CD34/CD123 expression in hematogones and leukemic lymphoblast to monitor therapy response and detect minimal residual disease. Patients and methods This case–control study was conducted on 40 newly diagnosed patients with B-lineage ALL. They were 14 boys and 26 girls with a mean age of 4.29±2.31 and a range from 2 to 10 years. Expression of CD34/CD123 by flow cytometry was carried out at diagnosis and at the end of induction. In addition, 20 patients with reactive bone marrow were included to asses hematogones. Results In the patient group, cells with dim CD45 were found in 24 cases, 75% of them expressed CD34 and 83.3% expressed CD123. In addition, cells with moderate CD45 were 16, all expressed CD34 and 87.5% of them expressed CD123. Thirty-two (80%) leukemic blasts expressed both CD34 and CD123; in contrast, in four (10%) patients neither antigen was expressed. In hematogones, immature hematogones (dim CD45, CD34+) did not express CD123, whereas 75% of mature hematogones (moderate CD45, CD34−) expressed CD123. On the other hand, at the end of induction, 18 (45%) leukemic blasts expressed both CD34 and CD123 and four (10%) showed no expression of both antigens. Conclusion This distinct pattern of CD34 and CD123 expression on B-ALL blasts (concordant) and hematogones (discordant) can help differentiate residual leukemic blasts from hematogones in patients with B-ALL.

Cluster of differentiation 97 as a biomarker for the detection of minimal residual disease in common acute lymphoblastic leukemia

Background Acute lymphoblastic leukemia (ALL) is a biologically heterogeneous disorder. Clinical parameters, immunophenotype, cytogenetic factors, and minimal residual disease (MRD) are among currently used factors in risk stratification and therapy determination of ALL patients. MRD is gaining importance nowadays for therapy efficacy, follow-up, and relapse risk estimation. Recent studies have highlighted potential markers that may improve the sensitivity of MRD detection by flow cytometry. Cluster of differentiation (CD) 97 is one of the markers that show overexpression in pediatric ALL. In this study, we aimed to assess the value of CD97 as a biomarker for MRD detection in pediatric ALL. Patients and methods This cohort study was conducted on 30 newly diagnosed patients with B-ALL. There were 16 male and 14 female patients with a mean age of 8.38±4.21. Twenty patients were in the low-risk group and 10 patients were in the high-risk group and were treated according to modified CCG 1991. A panel of monoclonal antibodies was used, with special emphasis on CD10, CD19, CD34, and CD97 at diagnosis and at day 14 postinduction of chemotherapy for MRD detection. Results The percentage of CD19/CD97, CD34/CD97, and CD10/CD97 at day 0 was 57.15±21.74, 57.73±21.20, and 57.87±20.77, whereas at day 14 it was 6.09±2.50, 10.67±8.89, and 5.97±2.44, respectively (P<0.001). CD97 was expressed in 81.5% of patients at diagnosis and was not detected at day 14 (P<0.001). One patient had blast counts more than 5% by light microscopy, whereas 29 patients had MRD more than 0.1 by flow cytometry at day 14 (P<0.001). Conclusion CD97 can be used for MRD tracing in pediatric ALL.

β-Thalassemia: Genotypes and Phenotypes

β-Thalassemias are extremely heterogeneous at the molecular level. More than 200 disease-causing mutations have been identified. The majority of mutations are single nucleotide substitutions. Rarely, β-thalassemia results from gross gene deletion. The degree of globin chain imbalance is determined by the nature of the mutation of the βgene. β0 refers to the complete absence of production of β-globin on the affected allele. β+ refers to alleles with some residual production of β-globin (around 10%). In β++, the reduction in β-globin production is very mild. The broad spectrum of β-thalassemia alleles can produce a wide spectrum of different β-thalassemia phenotypes. In this chapter, we review the molecular basis of the marked heterogeneity of the thalassemia syndromes or in other words the genotype-phenotype relationship in β-thalassemia.