Histiocytosis disorders in Northeast Egypt: epidemiology and survival studies (a 5-year study).

Histiocytosis disorders include a wide group of disorders characterized by monocytes, macrophages and dendritic cell infiltration of different tissues. There are few clinico-epidemiologic studies of such disease. Our study was designed to look at the clinico-epidemiological features and outcome of patients with histiocytosis disorders in Northeast Egypt. Twenty-seven cases with histiocytosis disorders accrued over a 5-year period were analyzed and classified as having unifocal, multifocal, or multisystem disease. They were 14 males and 13 females. Twenty-two patients representing 81.5% of cases were more than two years of age while 5 patients (18.5%) were less than 2 years. Lymphadenopathy was the commonest presentation (55.55%) followed by bone lesions (44.44%). Involvement was unifocal in 12, multifocal in 10, and multisystem in 5 cases. The histological features were relatively uniform regardless of the clinical severity, and consisted of Langerhans cells, eosinophils, histiocytes, plasma cells, giant cells and fibrosis. The treatment consisted of a combination of surgery, chemotherapy, and/or radiotherapy. Lymphadenopathy was the most common clinical presentation in our locality. Response to treatment was poor in patients with multisystem disease. Patients with age less than 2 years were more likely to have increased risk of morbidity and mortality, due to widespread disease.

Serum level of intercellular adhesion molecule-1 in children with malignant lymphoma.

OBJECTIVE: To estimate the serum levels of soluble intercellular adhesion molecule-1 (s-ICAM-1) in children newly diagnosed with lymphoma and to correlate levels of s-ICAM-1 in lymphoma patients with clinical stage, pathological types, clinical and laboratory data and patient outcome. SUBJECTS AND METHODS: Thirty-five children with newly-diagnosed malignant lymphoma (Non-Hodgkin's lymphoma, NHL: 23), Hodgkin's disease (HD: 12), and 8 apparently healthy subjects of matched age and sex taken as a control group were studied. For the patients and control group, the following tests were performed: complete blood count, and the following biochemical investigations: liver function tests, lactate dehydrogenase (LDH), and soluble ICAM-1 estimation using ELISA. In addition, for patients, pathological examination of lymph node biopsy for pathological grading, bone marrow aspiration and biopsy were done. Patients were observed for over 12 months or until death. RESULTS: Serum ICAM-1 increased more in HD and NHL than in the control group (p < 0.000); also s-ICAM-1 increased in advanced stages and high-grade NHL (p < 0.008, 0.04, respectively). LDH levels were higher in patients compared to controls (p < 0.000). There was a positive correlation between high levels of s-ICAM-1 and increased levels of LDH in HD (r = 0.72, p < 0.008) and a positive correlation between high levels of s-ICAM-1 and increased ALT in NHL patients. A positive correlation between s-ICAM-1 levels and the presence of B symptoms in HD and NHL, and a positive correlation between elevated s-ICAM-1 levels and worse outcome in HD and NHL were detected. CONCLUSIONS: The data indicate that in children with malignant lymphoma, high serum levels of ICAM-1 correlated with tumor aggressiveness, and quantification of s-ICAM-1 levels may identify a subgroup of children with worse prognosis. Therefore, detection of s-ICAM-1 levels in children with malignant lymphoma might represent an additional disease-associated marker for use in the clinical management of the patients.

Evaluation of bone mineral density in children with hemophilia: Mansoura University children hospital (MUCH) experience, Mansoura, Egypt.

BACKGROUND: Patients with hemophilia may be at risk for developing reduced bone mineral density (BMD) for a number of reasons such as recurrent hemoarthrosis and immobilization. AIM OF THE WORK: To assess the BMD in children with hemophilia and to correlate BMD with findings regarding the joint disease (hemophilic arthropathy). PATIENTS AND METHODS: Thirty hemophilic patients aged 4.97 +/- 3.64 years and 30 control healthy individuals (without joint disease) aged 5.09 +/- 3.64 years were selected from the hematology unit and outpatient clinic of MUCH respectively. Anthropometric measurements were carried out in all cases. Z-score was used for weight, height, and body mass index (BMI). Joint evaluation for hemophilic patients and controls was done using Colorado PE-0.5: Half point instrument before using dual energy X-ray absorptiometry (DEXA). DEXA scanning was performed in all hemophilic patients and controls focusing on L2-L4 vertebrae. RESULTS: There was no significant difference between hemophilic patients and controls as regard anthropometric measurements and their Z-score. There was a significant difference between hemophilic patients and controls as regard BMD and BMD Z-score (mean +/- SD) (BMD: 0.48 +/- 0.13 gm/m(2) for hemophilic patients vs. 0.55 +/- 0.14 gm/m(2) for control, p = 0.05, BMD Z-score: - 0.68 +/- 0.44 for hemophilic patients vs. 0.19 +/- 0.14 for controls p = 0.003). There was a significant difference between severe hemophilic patients (factor level assay less than 1%) and controls as regard BMD and BMD Z-score (BMD: 0.41 +/- 0.15 gm/m(2) for hemophilic patients vs. 0.55 +/- 0.14 gm/m(2) for controls, p = 0.01, BND Z-score: - 1.49 +/- 0.12 for hemophilic patients vs. 0.19 +/- 0.14 for controls p = 0.001). Also, in hemophilic patients, there was an inverse significant correlation between total joint evaluation scores and BMD Z-score (r = - 0.365, p = 0.04). CONCLUSIONS: Children with hemophilia may have reduced BMD compared with age- and gender-matched controls. This reduction in BMD was independent of differences in age and body size. Children with more established hemophilic arthropathy exhibited the lowest BMD and BMD Z-score. RECOMMENDATIONS: (1) Early detection of osteopenic hemophilic children using DEXA scanning, (2) bisphosphonates plus calcium for hemophilic children with reduced BMD, (3) evaluation of the effect of on demand vs. prophylaxis replacement therapy in hemophilic patients on BMD and hemophilic arthropathy.

Failure of puberty in Egyptian beta thalassemic patients: experience in north east region - Dakahlia province.

BACKGROUND: Endocrine complications in thalassemia major (TM) are classically considered to be the result of iron deposition in the endocrine glands. Hypogonadotropic hypogonadism, which still remains the commonest endocrinopathy in patients with TM, has been proven to be the result of hemosiderosis of the gonadotroph cells of the pituitary gland. THE AIM OF THE STUDY: To evaluate the prevalence of delayed puberty and hypogonadotropic hypogonadism in transfusion-dependent patients with beta-TM. PATIENT AND METHODS: Growth and sexual development of 40 patients with TM (20 males, 20 females) aged 12-22 years were evaluated. Thirty healthy individuals aged 12-20 years served as a control group. The following parameters were measured in every patient: age, sex, height, weight, body mass index (BMI) and Tanner's pubertal staging. For all patients, the following investigations were done: ophthalmological evaluation, audiograms, skeletal survey, echocardiography, serum ferritin, liver function tests, hepatitis profile, serum calcium, phosphorus and blood sugar. Thyroid, parathyroid hormones, serum follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T) and estradiol (E2) hormone were also measured. RESULTS: Failure of puberty was present in 80% of boys and 75% of girls aged 12-22 years. Gonadotropin insufficiency was found in most of the patients with lack of puberty. Arrested puberty was noted in five boys (25%) and six girls (30%). Ten girls (50%) did not menstruate, two (10%) had oligomenorrhea, one (5%) had irregular menstrual cycles and two (10%) developed secondary amenorrhea. Using univariate analyses and stepwise logistic regression analysis after adjustment for confounding factors, serum ferritin at the time of the study was identified as an independent risk factor for hypogonadotropic hypogonadism, with an odds ratio of 28.40 (95% confidence interval 3.25-245.15), P = 0.003 with a B value of 3.24 (standard error, 1.12). CONCLUSIONS: We conclude that failure of puberty is common in our thalassemic patients which necessitates newer protocols of treatment, correct blood transfusion and chelation therapy.

Once weekly recombinant human erythropoietin treatment for cancer-induced anemia in children with acute lymphoblastic leukemia receiving maintenance chemotherapy: a randomized case-controlled study.

BACKGROUND: Patients receiving chemotherapy for cancer often develop anemia, which can contribute to increased morbidity and reduced quality of life (QOL). Chemotherapy-induced anemia can be successfully treated using recombinant human erythropoietin (rHuEPO). AIM OF THE STUDY: To demonstrate the effectiveness of once-weekly (QW) rHuEPO dosing to effect improved hemoglobin levels, decreased transfusion use, and improved functional outcomes and QOL in pediatric leukemic patients (ALL) receiving maintenance chemotherapy. PATIENT AND METHODS: This was a prospective randomized, single-center, open-label, 12-week case-control study of epoetin alfa in pediatric patients with acute lymphoblastic leukemia (ALL) in remission receiving maintenance chemotherapy. Sixty patients were randomly assigned to receive either epoetin alfa (rHuEPO group = 30 cases, 17 males and 13 females, age; 6.8 +/- 2.33 years), or no epoetin alfa (control group = 30 cases, 16 males and 14 females, age; 6.76 +/- 2.28 years). Both groups were matched as regard age, sex, baseline Hb concentration, remission state, chemotherapy regimen, numbers and amount of blood transfusion, and leukemia state (both were low and standard risk). Epoetin alfa was administered at a dose of 450 IU/kg, once weekly, subcutaneously (s.c.) for 12 consecutive weeks. Endpoints were changes in hematologic and QOL parameters. RESULTS: Among the 30 patients evaluable for hematologic response, the mean increase in Hb from baseline to time of final evaluation was 3.08 +/- 1.48 g/dl (p < 0.001). An increase in Hb of > or = 2 g/dl, in the absence of blood transfusion, occurred in 70% of patients (21 of 30 patients) who were on the study for > or = 30 days. The overall response rate (Hb increase > or = 2 g/dl or Hb > or = 12 g/dl in the absence of blood transfusion) was 90% (27 of 30 patients). In 30 patients who were evaluable for QOL assessment, epoetin-alpha therapy was found to significantly (p < 0.001) improve mean cancer linear analog scale (CLAS) scores for energy level, ability to perform daily activity, and overall QOL from baseline to the time of final evaluation. QW epoetin-alpha was found to be well tolerated. CONCLUSION: Treatment with QW epoetin-alpha was found to increase Hb levels, decrease transfusion requirement, and improve functional status and QOL in anemic patients with ALL in maintenance receiving chemotherapy. The once-weekly schedule is convenient, safe, and may reduce the burden on patients, parents, and their caregivers by reducing the number of visits to the clinic.

Pattern of iron chelation therapy in Egyptian beta thalassemic patients: Mansoura University Children's Hospital experience.

BACKGROUND: The simultaneous use of deferoxamine (DFO) and deferiprone (DFP) has an additive effect in iron excretion in transfusion-dependent thalassemic patients. AIM OF THE WORK: To evaluate the efficacy and safety of a prospective alternating therapy with DFO and DFP in patients with beta-thalassemia major (TM) and increased serum ferritin with DFO monotherapy alone. PATIENT AND METHODS: Sixty patients with beta-TM (mean age +/- SD, 13.05 +/- 6.1, range 10-20 years) with iron overload (serum ferritin > 2000 ng/ml) were studied. They received DFO at a daily dose of 40 mg/kg/day for 5-7 nights/week for the past several years. These patients were randomly assigned either to continue treatment with DFO alone (DFO group, n = 30) or prospectively receive additional alternating therapy with DFP at 75 mg/kg/day for 4 days/week and DFO for the other 2 days/week (alternating therapy group, n = 30). The efficacy of both groups was assessed by measurements of serum ferritin, echocardiography, and 24 h urine iron excretion (UIE) levels throughout 1 year follow-up. RESULTS: In the 60 evaluable patients, the mean serum ferritin ( +/- SD) fell dramatically from 4500 ( +/- 1250) ng/ml at the start of the study to 1250 ( +/- 750) ng/ml (alternate therapy group; P < 0.001) at the end of the study. There was also a significant improvement in the myocardial function as assessed by the ejection fraction (P < 0.002) and fractional shortening (P < 0.01) in those patients on alternate therapy for 1 year. Their mean urinary iron excretion elevated from 0.41 +/- 0.27 to 0.76 +/- 0.49 mg/kg/24 h (P < 0.003). There was a significant difference between both groups as regard the studied parameters at the end of the study. Whereas, there was no statistical difference as regard the studied parameters at the start and the end of the study in the DFO group. No significant adverse effects had occurred in both groups that necessitated withdrawal from the study. CONCLUSIONS: beta-Thalassemic major patients with transfusional iron overload can be safely and effectively treated with an alternate therapy of DFO/DFP with a progressive fall in the mean serum ferritin and significant improvement of myocardial performance.

Impact of long-term oral iron supplementation in breast-fed infants.

OBJECTIVE: To weigh benefits of oral iron supplements on infant's growth against its potential hazards. METHODS: 248 exclusively breast-fed infants aged 4-6 months were consecutively enrolled and divided into treatment group given iron containing multivitamin (TG = 198) and control group (placebo, PG = 50) given the same multivitamin but without is subdivided according to clinical assessment into group A (well nourished) and group B (malnourished); both were further stratified according to basal blood iron status. Assessment was done after 6 and 12 months with concurrent collection of morbidity parameters (diarrhea and fever). Data were normalized and analyzed using SPSS and Eurogrowth softwares. RESULTS: After 6 months treatment, weight and length gain was better in TG compared to placebo especially evident in anemic malnourished infants (P 0.05). Morbidity risk was linked to immunologic background of infant; odds ratio for diarrhea and fever was higher in malnourished compared to well nourished (P 0.05) or iron therapy (P for well-nourished non-anemic treatment vs PG > 0.05). CONCLUSION: Oral iron supplementation resulted in better effects on growth velocity of breast fed infants especially those who were initially malnourished and anemic or at least iron depleted, with less marked morbidity than in iron replete infants.

Coagulation disorders and inhibitors of coagulation in children from Mansoura, Egypt.

Disorders of coagulation in children often prove challenging to the medical care team. The aims of this study were to assess the spectrum and prevalence of coagulation disorders among children attending Mansoura University Children Hospital (MUCH), Mansoura, Egypt. A total of 105 pediatric patients were referred to MUCH. They were divided into two groups: congenital coagulation disorders (75 cases, age 45.36 +/- 48.59 months), and acquired coagulation disorders (30 cases, age 56.13 +/- 61.61 months). All patients were subjected to thorough history taking including the nature of bleeding, family, past history, mode of inheritance, and detailed physical findings. Hemostatic tests included: platelet count, bleeding time (BT), prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT). Specific tests in the congenital group include assay of coagulation factors according to each disorder, Von Willebrand factor assay, ristocetin aggregation test, APTT mixing study for detection of inhibitors in complicated hemophilia cases, F VIII C to VWAg ratio with cut off 0.7 for detection of carriers in some hemophilia A families. Congenital disorders constituted 71.4% of the studied cases vs. 28.6% for acquired disorders. Hemophilia A (42.85%), hemophilia B (14.28%) and liver diseases (14.28%) represented the majority of the studied cases. Mild and moderate cases of hemophilia A and B are more frequent than severe cases in both types. Male sex is more frequent than female in the congenital group (94.7 vs. 5.3%, P < 0.001). Direct correlation existed between factor level assay and severity of hemophilia (r = 0.73, P = 0.006). Three mothers and one sister were identified as carrier out of four families. Anti-clotting factors inhibitor was detected in 18.2% of patients with hemophilia A and in 9.1% with hemophilia B. In conclusion, our study found that hemophilias are the most prevalent congenital coagulation disorders among children. Attention must be given for detection of hemophilia carriers and inhibitors of clotting factors.