Risk factors of childhood acute lymphoblastic leukaemia: a case-control study

The Alexandria Cancer Registry in 1992 reported that Acute Lymphoblastic Leukaemia [ALL] constituted 24.7% of childhood malignancies among male children and 19.2% among female children. This relative high magnitude of ALL in Egypt needs to be studied in depth. The aim is to reveal the different risk factors related to development of the childhood ALL and provide essential data for planning preventive programs. A hospital based case control study was carried out in two hospitals: Alexandria University Children Hospital and School Students Hospital. Data collection was carried using a structured interview schedule. All newly diagnosed cases of ALL during the period from March, 2003 - 31[st] December, 2004 were included in the case series [90 cases]. For each case, two controls were randomly recruited [180] of matched age and sex with ALL cases. The mean age of cases was 4.58 +/- 2.35 years. The ratio of boys to girls was 2.1:1. The final model of multiple logistic regression analysis revealed that first born or only born child and birth weight >/= 3500 gm, consanguinity, fathers' smoking before conception, child exposure to hydrocarbons/benzene, electromagnetic field sources, family history of blood cancers, maternal history of prior fetal losses, some infections, allergies, exposure to radiation or intake of medications during pregnancy, also different childhood diseases all were significant contributing factors that increased risk of ALL, whereas exclusive breast-feeding and early day-care attendance were associated significantly with decreased risk of ALL. The consistency of results of current work with several other research works can support the identification of specific possible risk factors. The research points to specific environmental, social, health and biological factors that need to be addressed. Further research is needed. The data presented in this work can be used to formulate hypotheses

Study of caspase-3 level in relation to prognostic risk factors in children with acute lymphoblastic leukemia

Apoptosis refers to a biochemically regulated process of automated cell death mediated through a highly organized network of interacting proteases. Malignant transformation of hematopoietic progenitors into leukemic cells results in defects in the cell cycle regulation; including defects in apoptosis. Multiple mechanisms may account for why leukemic cells become resistant to chemotherapy. One common cause includes defects in the cell inherent programmed cell death [apoptosis]. This study was conduced on 20 children with newly diagnosed ALL and 10 controls. Our aim was to evaluate the level of caspase-3 among them and relate it to prognostic factors. It can be concluded that caspase-3 level after induction therapy proved to be a significant predictor of remission stage especially for B-ALL. CD10 positive cases also showed a significant difference between caspase-3 level before and after induction therapy. The same was demonstrated with low risk cases. We can also conclude that failure of caspase-3 level to increase after induction is associated with poor prognosis

Comparative study for the detection of 563 C-T G6PD mutation using restriction enzyme assay and amplification and refractory mutation system [ARMS]

G6PD deficiency is the most common enzyme disorder in humans and is characterized by considerable biochemical and molecular heterogeneity. The prevalence of G6PD deficiency in the Middle East varies greatly, ranging from 1% among Egyptians to 11.5% among Iranians. G6PD Mediterranean [563 C-T] mutation is probably the most common G6PD variant in the world. The relative frequency of this mutation ranges from 70% among Egyptians to 97% for Kurdish Jews. This study was conducted on 30 Egyptian pediatric G6PD-deficient patients. Quantitation of G6PD enzyme was performed before molecular analyses, during, and one month after the hemolytic attack. The frequency of the mutation was investigated using two methods; the reference method; RFLPs and ARMS technique. The aim of this study was to compare both methods. Both methods gave identical results, yet ARMS method is easier and less time consuming

Blood antioxidant activity in preterm neonates with and without respiratory distress

Concentrations of circulating antioxidants were considered being important in the pathogenesis of diseases in preterm infants. Plasma total antioxidant status [TAS], some preventive and chain breaking antioxidants were studied in 20 preterm infants with respiratory distress on the first and fifth day of life. Ten preterm infants without respiratory distress and ten full term healthy neonates were also evaluated. On the first day of life, the plasma TAS, uric acid, transferrin % saturation levels were significantly high in the preterm infants with respiratory distress. On the contrary, serum albumin, total iron binding capacity [TIBC], ceruloplasmin, red blood cell superoxide dismutase [SOD] and red blood cell glutathione peroxidase [GSHPx] levels were significantly low, By the fifth postnatal day, plasma TAS, uric acid, transferrin % saturation, and red cell GSHPx levels were significantly decreased while, serum bilirubin, ceruloplasmin, TIBC and red cell SOD levels were significantly increased in preterm infants with respiratory distress. The duration of oxygen therapy was negatively correlated with plasma TIBC and was positively correlated with transferrin % saturation on the first and fifth day of life. Plasma TAS, uric acid, serum bilirubin and transferrin % saturation were significantly high while, serum albumin and TIBC were significantly low in non-survived preterm infants who had respiratory distress. Recurrent apneas, elevated uric acid levels and decreased TlBC on the first day of life in addition to increased duration of oxygen therapy and high transferrin % saturation on the fifth day of life, were significant predictors of mortality. These major postnatal changes in blood antioxidant activity in preterm infants with respiratory distress may influence their susceptibility to oxygen toxicity

Study of soluble vascular cell adhesion molecule one [sVCAM-1] and von will brand factor [vWF] in children with beta thalassemia major

There is a strong evidence of endothelial cell activation in beta thalassemia and vascular complications in these patients are more frequent. The objective of this work is to study the levels of circulating soluble vascular cell adhesion molecule [sVCAM-1] and Von Will brand factor [vWF] as parameters of endothelial cell activation in a group of children with P-thalassemia major, and their relation to duration of the disease. The study was conducted on 35 patients with P-thalassemia major, recruited from the hematology outpatient clinic of Alexandria University Children's Hospital, who were divided into two groups. Group I included 15 young children with a disease duration 55 years and group I1 included 20 older children and adolescents with disease duration > 5 years. Ten apparently healthy children of matching age and sex served as control group. Children were subjected to full clinical examination with special emphasis on signs of vascular affection. Serum levels of: sVCAM-1 were measured by enzyme- linked immunosorbent assay [ELISA], and vWF by radial immunodiffusion. The results showed that 4 of the studied patients had pulmonary hypertension and one patient suffered from left lower limb deep vein thrombosis. Soluble vascular cell adhesion molecule-1 results demonstrated significantly higher levels in both thalassemic groups in comparison with controls and non-significant difference between the two groups themselves. A positive correlation was found between sVCAM-1 levels and serum ferritin in both groups, and with vWF in-group II only [P=0.007, 0.042 and 0.031 respectively]. There was a non-significant difference between the levels of vWF in both thalassemic groups and controls [k0.093]. There was no statistically significant difference as regards sVCAM-1 and vWF levels in non-splenectomized and splenectomized children in both groups [P=0.545, P=0.219]

Conclusion: measurement of sVCAM-1 might be a useful marker for the follow up of vascular disease in transfusion dependent thalassemic patients

Varicella vaccine: a clinical and immunological study in healthy and immunocompromised children with acute lymphoblastic leukemia

The increased number and long term survival of immunocompromised children with acute lymphoblastic leukemia [ALL] might lead to their affection with fatal varicella, The objective of this study was to investigate the safety and immunogenicity of varicella vaccine in a group of children with ALL and non-immune siblings of leukemic children. Forty-five children with ALL and 26 healthy siblings of children with ALL all with negative history of chicken pox were immunized with live attenuated varicella vaccine [Oka strain]. At the time of the study, thirty-five were still receiving maintenance chemotherapy [group I] and 10 have completed their maintenance therapy [group II]. Group III included the 26 healthy siblings of children with ALL. The control group comprised 15 children with ALL who acquired natural varicella virus infection [group IV]. Serum IgG antibodies against varicella zoster virus [VZV] were measured by ELISA at baseline and at 3 and 6 months after vaccination for leukemic children and at baseline and 6 weeks after vaccination in healthy siblings, and once for the control group. The results showed that patients in groups II and III tolerated well the vaccine with no side effects. However, varicella form rash occurred in 5 [14%] children out of 35 cases of group I, Three of them were treated with oral acyclovir. Zoster occurred in 3 cases [8.5%] of group I. Seroconversion in 71.1% of children of group I and 70% of group II after one dose and in 91.4% of group I and 80% of group II after a second dose of the vaccine. The mean serum level of [VZV] IgG was significantly higher in groups III and IV than groups II and I after one dose of the vaccine [F=24.765, P<0.001]. The mean serum level of [VZV] IgG was significantly lower in ALL in children of group I after 6 months of vaccination compared to the healthy siblings [P<0.001]. However, during 3 years follow up; breakthrough varicella occurred in only one case of group II after household exposure. It was mild with no fever and with only 7 skin lesions

Conclusion: varicella vaccine administered carefully with close follow-up is safe and beneficial to leukemic children. The vaccine-induced immunity appeared effective in preventing or modifying chicken pox after exposure to natural disease in ALL children