Serum progranulin levels in paediatric patients with Gaucher disease; relation to disease severity and liver stiffness by transient elastography.

BACKGROUND: Non-invasive screening for liver fibrosis using transient elastography (TE) could be of value in the management of Gaucher disease (GD). Progranulin (PGRN) is a novel disease modifier in GD and an independent marker of liver fibrosis. OBJECTIVES: We determined PGRN levels in paediatric patients with GD and assessed its role as a potential marker for disease severity and relation to liver stiffness by TE. METHODS: Fifty-one GD patients (20 had type 1 and 31 had type 3) with a median age of 9.5 years were compared to 40 age- and sex-matched healthy controls and were studied focusing on visceral manifestations, neurological disease, haematological profile and PGRN levels as well as abdominal ultrasound and TE. Patients were on enzyme replacement therapy (ERT) for various durations and those with viral hepatitis infection were excluded. RESULTS: By TE, 14 GD patients (27.5%) had elevated liver stiffness ≥7.0 kPa. Liver stiffness was significantly higher in type 1 GD patients than type 3 (P = .002), in splenectomized patients (P = .012) and those with dysphagia (P < .001). Liver stiffness was positively correlated with age of onset of ERT (P < .001). PGRN levels were significantly lower in GD patients compared with controls (P < .001). PGRN was significantly lower in GD patients with squint (P = .025), dysphagia (P = .036) and elevated liver stiffness (P = .015). PGRN was positively correlated with white blood cell count (r = .455, P = .002) and haemoglobin (r = .546, P < .001), while negatively correlated with severity score index (r = -.529, P < .001), liver volume (r = -.298, P = .034) and liver stiffness (r = -.652, P < .001). CONCLUSIONS: Serum PGRN levels were associated with clinical disease severity and elevated liver stiffness in paediatric GD patients.

Reticulocyte Hemoglobin Content (Ret He): A Simple Tool for Evaluation of Iron Status in Childhood Cancer.

BACKGROUND: Cancer-related anemia is a common complication of cancer and its treatment that may be mediated by nutritional deficiency or inflammatory cytokines inhibiting erythropoiesis. AIM: We evaluated the value of reticulocyte hemoglobin content (Ret He) as a marker of iron availability for erythropoiesis in childhood cancer and the impact of oral iron supplementation on hematologic parameters in patients with low Ret He. MATERIALS AND METHODS: This prospective study included 100 pediatric patients with cancer on chemotherapy who were screened for the presence of anemia. Patients with anemia underwent testing for complete blood count including Ret He on Sysmex XE 2100 and assessment of reticulocyte count, serum iron, serum ferritin, transferrin saturation, total iron-binding capacity, and C-reactive protein. Patients were classified according to their level of Ret He into normal or low Ret He using a cutoff level of 28 pg. Patients with low Ret He were subjected to 6 weeks' treatment with oral ion and were followed up with complete blood count and iron profile. RESULTS: Thirty-one (77.5%) patients had normal Ret He, and 9 (22.5%) had low Ret He. Ret He was positively correlated with red cell indices, but not with iron parameters. After oral iron supplementation, a significant increase in hemoglobin, reticulocyte count, and iron was found. CONCLUSIONS: We suggest that Ret He could be used as an easy and affordable tool for the assessment of iron deficiency anemia in childhood cancer during chemotherapy treatment. A trial of oral iron in patients with low Ret He may be useful to correct the associated anemia.

Silent bleeding in children and adolescents with immune thrombocytopenia: relation to laboratory parameters and health related quality of life.

Occult hemorrhage can occur in any internal organ in ITP patients. Four sites of occult hemorrhage require attention including microscopic hematuria, fecal occult blood loss, retinal hemorrhage, and silent intracranial hemorrhage. The aim of this study was to investigate the frequency of subclinical bleeding in children with ITP and its relation to clinical and laboratory disease parameters including bleeding score and health related quality of life. This cross-sectional study included 40 ITP patients recruited from the Pediatric Hematology/Oncology unit, Children's Hospital, Ain Shams University, Cairo, Egypt. Inclusion criteria were patients with ITP (acute, persistent or chronic) having platelet count of 20,000/cmm or less at diagnosis/relapse, patients with overt bleeding and patients with secondary ITP were excluded. Occult blood in stools and urine analysis, fundus examination, and non-contrast brain MRI for microbleeds were done. Out of the forty included patients, 24 had chronic, 11 had acute and 5 had persistent ITP. Eleven patients had occult bleeds. Two patients had occult blood in stools, five had microscopic hematuria, one had retinal bleeds and three patients had brain microbleeds. Their mean age was 10.23 ± 4.18 years and their mean initial bleeding score was 2.55 ± 0.82. Nine patients with occult bleeding were chronic, one persistent and one acute ITP patients. There were no significant differences between patients with occult bleeding and those without as regards the initial bleeding score, platelet counts and hemoglobin level, as well as the mean platelet counts and mean hemoglobin level over the disease duration (p > 0.5). The scoring of the parent's life, Child and parents' quality of life was low in 3 out of 11 patients with occult bleeding. There was no significant difference between patients with occult bleeding and those without as regards the ITP child and parents' quality of life items (p = 0.850 and 0.511 respectively). Our results suggest that subclinical bleeding is a potential risk in children with ITP, more commonly chronic ITP patients. We could not demonstrate a significant relation of occult bleeding to the laboratory findings, bleeding score, and the ITP health quality of life; nevertheless, the significance of the routine assessment of occult bleeding in ITP and the identification of high-risk patients require additional studies.

Egyptian experience in Langerhans cells histiocytosis: frequent multisystem affection and reactivation rates.

Background: Histiocytoses are unique disorders; their clinical presentations vary from self-healing lesions to life-threatening disseminated disease. Objectives: We aimed to evaluate the different clinical presentations, frequency of reactivations, and treatment outcome of Langerhans cell histiocytosis among Egyptian children. Methods: we restrospectively analyzed the data of 37 Langerhans cell histiocytosis patients (LCH) registered at Ain Shams University Children's Hospital for clinicopathological features, treatment modalities and their outcomes. Results: Twenty seven (73%) of the studied patients with LCH had multisystem disease (MS), 24 (88.9%) of them had risk organ involvement (MS RO+) and only 3 without risk organ (MS RO-). Most of the patients received LCH III protocols. Eleven patients (29.7%) had reactivations with median time till reactivation of 17 months (IQR 5-23).Reactivation rates were 40% and 50% in patients with no evidence of active disease (NAD) and those with active disease better (AD better) at week 6 evaluation respectively (p = 0.71).We report 9 deaths (all had MS RO+, two died after reactivation and 7 had progressive disease. The 5 years EFS and OS were 49.4% and 81.2% respectively. Risk stratification did not significantly affect the EFS or OS (p = 0.64 and p = 0.5 respectively). Conclusion: A high reactivation rate was encountered in children with LCH and MS-RO + irrespective of 6 weeks response to induction therapy. A high mortality in patients with progressive disease necessitates a possible earlier aggressive salvage in such group.

Inner Ear Complications in Children and Adolescents with Sickle Cell Disease.

Hearing impairment is a reported complication of sickle cell disease, yet inner ear pathology is not fully understood. The study purpose was to examine the patterns of inner ear involvement in patients with sickle cell disease by magnetic resonance imaging (MRI) and to assess its association with auditory functions. A cross-sectional study included 22 children with sickle cell disease examined for inner ear pathology by audiogram, MRI inner ear and transcranial Doppler (TCD) with revision of their hospital records for transfusion, chelation and hydroxyurea (HU) therapy. Abnormal MRI in the form of intrinsic T1 hyperintensity within the lumen of inner ear structures and cochlear neuropathy was found in five (22.7%) patients; left middle cerebral artery (MCA) flow velocity was higher in patients with abnormal MRI (83.4 ± 5.3 cm/sec) compared to normal MRI (68.2 ± 11.1 cm/sec) (p = 0.015), however, none of the patients had TCD of >170 cm/sec. There was no significant difference between patients with normal and abnormal MRI as regards hearing level and speech audiometry. Sensorineural hearing loss (SNHL) was present in two (9.1%) and conductive hearing loss (CHL) in two (9.1%) patients. There was a significant negative correlation between right ear mean hearing level and right MCA flow velocity and significant negative correlation between left ear mean hearing level and basilar artery (BA) flow velocity. We concluded that inner ear pathology is not uncommon in asymptomatic patients with sickle cell anemia, yet it did not correlate with hearing impairment and may occur with normal TCD results.

Evaluation of continuous glucose monitoring system for detection of alterations in glucose homeostasis in pediatric patients with ß-thalassemia major.

BACKGROUND: Disturbances of glucose metabolism are common in ß-thalassemia major (ß-TM). AIM: This study was conducted to assess the pattern of glucose homeostasis in pediatric ß-TM patients comparing oral glucose tolerance test (OGTT) and continuous glucose monitoring system (CGMS). METHODS: Two-hundred ß-TM patients were studied and those with random blood glucose (RBG) ≥7.8 mmol/L (140 mg/dL) were subjected to OGTT, insertion of CGMS and measurement of fasting C peptide, fasting insulin, and hemoglobin A1c (HbA1c). RESULTS: Twenty patients (10%) had RBG ≥ 7.8 mmol/L. Using OGTT, 6 out of 20 patients (30%) had impaired glucose tolerance (IGT) while 7 (35%) patients were in the diabetic range. CGMS showed that 7/20 (35%) patients had IGT and 13 (65%) patients had diabetes mellitus (DM); 10 of the latter group had HbA1c readings within diabetic range. The percentage of diabetic patients diagnosed by CGMS was significantly higher than that with OGTT (P = 0.012). Serum ferritin was the only independent variable related to elevated RBG. All ß-TM patients with DM were non-compliant to chelation therapy. CONCLUSIONS: The use of CGMS in the diagnosis of early glycemic abnormalities among pediatric patients with ß-TM appears to be superior to other known diagnostic modalities.

Expression of CD4+ CD28null T lymphocytes in children and adolescents with type 1 diabetes mellitus: Relation to microvascular complications, aortic elastic properties, and carotid intima media thickness.

BACKGROUND: Cardiovascular risk in type 1 diabetes mellitus (T1DM) is associated with endothelial dysfunction, inflammation, and altered immunity. CD4+ CD28null T-cells are a subset of long-lived cytotoxic CD4+ T-lymphocytes with proatherogenic and plaque-destabilizing properties. We hypothesized that the frequency of CD4+ CD28null T-cells may be altered in T1DM and related to vascular complications. AIM: To assess the percentage of CD4+ CD28null T-lymphocytes in children and adolescents with T1DM and their relation to vascular structure and glycemic control. METHODS: Totally 100 patients with T1DM were divided into 2 groups according to the presence of microvascular complications and compared with 50 healthy controls. CD4+ CD28null T-lymphocytes were analyzed using flow cytometry. Aortic elastic properties and carotid intima media thickness (CIMT) were assessed. RESULTS: Aortic stiffness index and CIMT were significantly higher among patients compared with healthy controls while aortic strain and distensibility were decreased. The percentage of CD4+ CD28null T-cells was significantly higher in patients with and without microvascular complications compared with controls. High frequency of CD4+ CD28null T-cells was found among patients with microalbuminuria or peripheral neuropathy. Patients with CD4+ CD28null T-cells ≥10% had higher HbA1c, urinary albumin creatinine ratio, aortic stiffness, and CIMT. CD4+ CD28null T-cells were positively correlated to HbA1c, aortic stiffness index, and CIMT. CONCLUSIONS: Changes in aortic elastic properties and increased CIMT among young patients with T1DM may enable the recognition of preclinical cardiac impairment. The correlation between CD4+ CD28null T-cells and assessed parameters of vascular structure highlights the role of altered immune response in the occurrence of diabetic vascular complications.

Development of anti-velaglucerase alfa antibodies in clinical trial-treated patients with Gaucher disease.

Anti-drug antibodies may develop with biological therapies, possibly leading to a reduction of treatment efficacy and to allergic and other adverse reactions. Patients with Gaucher disease were tested for anti-drug antibodies every 6 or 12weeks in clinical studies of velaglucerase alfa enzyme replacement therapy, as part of a range of safety endpoints. In 10 studies between April 2004 and March 2015, 289 patients aged 2-84years (median 43years) were assessed for the development of anti-velaglucerase alfa antibodies. Sixty-four patients were treatment-naïve at baseline and 225 patients were switched to velaglucerase alfa from imiglucerase treatment. They received velaglucerase alfa treatment for a median of 36.4weeks (interquartile range 26.4-155.4weeks). Four patients (1.4%) became positive for anti-velaglucerase alfa IgG antibodies, two of whom had antibodies that were neutralizing in vitro, but there were no apparent changes in patients' platelet counts, hemoglobin levels or levels of CCL18 and chitotriosidase, suggestive of clinical deterioration after anti-velaglucerase alfa antibodies were detected, and no infusion-related adverse events were reported. Less than 2% of patients exposed to velaglucerase alfa tested positive for antibodies and there was no apparent correlation between anti-velaglucerase alfa antibodies and adverse events or pharmacodynamic or clinical responses.

One-Year Prospective Study of Community Acquired Influenza and Parainfluenza Viral Infections in Hospitalized Egyptian Children with Malignancy: Single Center Experience.

BACKGROUND: Respiratory viruses are widespread in the community and easily transmitted to immunocompromised patients. AIMS: Assess the prevalence of community-acquired respiratory viral infections among children with cancer presenting with clinical picture suggestive of lower respiratory tract infections (LRTIs), and evaluate its risk factors and prognosis. METHODS: Over a year, 90 hospitalized children with malignancy and LRTIs recruited, subjected to clinical assessment, investigated through hematology panel, blood culture, chest x-ray, CT chest and PCR for influenza A and B, parainfluenza (PIV) types 1 and 3 viruses, and respiratory syncytial virus (RSV), and prospectively followed up for the clinical outcome. RESULTS: Viral pathogens were identified in 34 patients (37.7%), with a seasonal peak from April to May. The most frequently detected virus was influenza virus [type A (16 cases; 47%), type B (4 cases; 12%)] followed by parainfluenza virus [PIV1 (9 cases; 26%), PIV3 (3 cases; 15%)], and none had RSV. Bacteria were identified in 26 patients, fungi in four, mixed infections [bacterial/viral and bacterial/fungal] in 13, and 36 cases had unidentified etiology. The majority of patients with influenza and parainfluenza infections had hematological malignancy, presented with fever, and had mild self-limited respiratory illness. Five patients with mixed viral and bacterial infection had severe symptoms necessitating ICU admission. Six patients died from infection-related sequelae; two had mixed PIV and Staphylococcal infections. CONCLUSIONS: Community acquired influenza and parainfluenza infections are common in pediatrics patients with malignancy, either as isolated or mixed viral/bacterial infections. Clinical suspicion is essential as hematological and radiological manifestations are nonspecific. Rapid diagnosis and management are mandatory to improve patients' outcome.

Survival analysis after diagnosis with malignancy of Egyptian adolescent patients: a single-center experience.

BACKGROUND: Adolescents with malignancy represent a unique population in oncology, receiving care in pediatric or adult oncology institutions. Previously, adolescents and young adults (AYAs) had good survival rates; yet in the last few decades, AYAs have shown inferior survival rates compared with children due to the increasingly reported AYA-specific malignancies with poor survival rates. This study evaluates the clinicoepidemiological aspects of adolescent cancer diagnosed in a Pediatric Oncology Unit over a 10-year period, the associated risk factors, and the survival rate. METHODS: Retrospective data analysis of patients aged 10 to 19 years diagnosed in the Pediatric Oncology Unit, Children's Hospital Ain Shams University, Cairo, Egypt, during the period from January 1, 2000 to January 1, 2010. RESULTS: There were 158 patients (20% of total number of patients diagnosed during the same period), 84 male (53.2%) and 74 female (46.8%). Hematological malignancies were the most common (91.8%), with acute lymphoblastic leukemia being the most prevalent malignancy (61.5%), and solid tumors represented 8.2% of the total number of patients. The 5- and 10-year overall survival rates were 45.2% and 40.2%, respectively. The 5- and 10-year event-free survival rates for hematological malignancies were 39.9% and 37.3%, and for solid tumors it was 36.4%. Infection was the main cause of death (50%). CONCLUSIONS: Age-related survival gap exists for adolescent cancer patients compared with children. Further studies are needed to provide evidence about optimal treatment regimens in this age group.

Management of transfusion-dependent ß-thalassemia (TDT): Expert insights and practical overview from the Middle East.

ß-Thalassemia is one of the most common monogenetic diseases worldwide, with a particularly high prevalence in the Middle East region. As such, we have developed long-standing experience with disease management and devising solutions to address challenges attributed to resource limitations. The region has also participated in the majority of clinical trials and development programs of iron chelators and more novel ineffective erythropoiesis-targeted therapy. In this review, we provide a practical overview of management for patients with transfusion-dependent ß-thalassemia, primarily driven by such experiences, with the aim of transferring knowledge to colleagues in other regions facing similar challenges.

Hemophagocytic lymphohistiocytosis in Egyptian children: diagnosis, treatment challenges, and outcome.

BACKGROUND: Hemophagocyticlymphohistiocytosis (HLH) is a spectrum of immune activation which could be genetically determined, or secondary to an underlying illness. Our aim was to present the clinico-genetic aspects of HLH among Egyptian children and to evaluate the patterns of reactivation and outcome with illustrations of overlap manifestations. RESEARCH DESIGNAND METHODS: We retrospectively collected the data of 55 patients with HLH, registered at Ain Shams University Children's Hospital,Cairo, Egypt. RESULTS: Median age at diagnosis was 19 months (range 2-180), 33 patients (60%) fulfilled the diagnostic HLH criteria at presentation. Fourteen (25.45%) patients had secondary HLH, 15 (27.27%) patients had genetically documented familial HLH (11 had variants in UNC13D gene and one in PRF1 gene), 3 had Griscelli and Chediak-Higashi syndromes. Sixteen patients (29.1%) had reactivations, 8 (50%) of them had molecularly confirmed HLH. We report the death of 40 patients, the median duration from the diagnosis to death of 5 months mostly due to disease activity. CONCLUSIONS: This study confirms that the nonspecific signs and symptoms of HLH are challenging. Genetic testing, though expensive and sophisticated, is integral for the diagnosis. The difficulty in finding non-related donors for stem cell transplantation and the early reactivations are the causes of the inferior outcome.

Flow cytometric assessment of circulating platelet and erythrocytes microparticles in young thalassemia major patients: relation to pulmonary hypertension and aortic wall stiffness.

Heart disease is the leading cause of mortality and morbidity in ß-thalassemia major (ß-TM). Aggregability of abnormal red cells and membrane-derived microparticles (MPs) stemming from activated platelets and erythrocytes are responsible for thrombotic risk. We measured platelet and erythrocyte MPs (PMPs and ErMPs) in 60 young ß-TM patients compared with 40 age- and sex-matched healthy controls and assessed their relation to clinicopathological characteristics and aortic elastic properties. Patients were studied stressing on transfusion history, splenectomy, thrombotic events, chelation therapy, hematological and coagulation profiles, flow cytometric measurement of PMPs (CD41b(+) ) and ErMPs (glycophorin A(+) ) as well as echocardiographic assessment of aortic elastic properties. Aortic stiffness index and pulmonary artery pressure were significantly higher, whereas aortic strain and distensibility were lower in TM patients than controls (P < 0.001). Both PMPs and ErMPs were significantly elevated in TM patients compared with controls, particularly patients with risk of pulmonary hypertension, history of thrombosis, splenectomy or serum ferritin >2500 µg/L (P < 0.001). Compliant patients on chelation therapy had lower MPs levels than non-compliant patients (P < 0.001). PMPs and ErMPs were positively correlated to markers of hemolysis, serum ferritin, D-dimer, vWF Ag, and aortic stiffness, whereas negatively correlated to hemoglobin level and aortic distensibility (P < 0.05). We suggest that increased MPs may be implicated in vascular dysfunction, pulmonary hypertension risk, and aortic wall stiffness observed in thalassemia patients. Their quantification could provide utility for early detection of cardiovascular abnormalities and monitoring the biological efficacy of chelation therapy.

Spinal cord compression in childhood pediatric malignancies: multicenter egyptian study.

OBJECTIVES: To assess the magnitude of management delay of pediatric malignant spinal cord compression (MSCC). METHODS: Twenty-four patients with MSCC were recruited from 3 Egyptian pediatric oncology centers and assessed for MSCC clinical presentations, evaluation, and treatment response. RESULTS: There was a median delay of 42 days from the onset of symptom until confirmed diagnosis. All studied patients presented inability to walk; 79% had pain (more in older patients) and 17% had sphincteric dysfunction. A total of 58.3% had a single level of cord compression, 41.7% had multiple levels. Thoracic spine was commonly involved (41%). Final diagnosis was: neuroblastoma (29.2%), soft-tissue sarcomas (20.8%), neuroectodermal tumor (16.6%), non-Hodgkin lymphoma (12.5%), astrocytoma (4.2%), malignant teratoma (8.4%), Wilms tumor (4.2%), and leukemia (4.2%). Magnetic resonance imaging of the spine was diagnostic in all cases. A total of 83.3% of patients received emergency steroid therapy and 75% showed improvement. Disease-specific therapy was multimodality therapy in 88.5% with 71.42% showing improvement. Lymphomas had the best neurological outcome (100%) followed by soft-tissue sarcomas (80%) and neural tumors (72.7%). The 3-year overall survival was 79.2%. CONCLUSIONS: Spinal cord compression is a serious complication and unacceptable management delay can result in preventable loss of function. Emergency magnetic resonance imaging evaluation is the most sensitive diagnostic imaging. Majority of patients improve after definitive therapy.

Bone mass and biochemical markers of bone turnover in children and adolescents with chronic immune thrombocytopenia: relation to corticosteroid therapy and vitamin D receptor gene polymorphisms.

Optional drug therapy in refractory chronic immune thrombocytopenia (ITP) includes standard oral, pulsed high-dose steroid therapy, intravenous gamma globulin, anti-D, and immunosuppressive therapy or thrombopoietin receptor agonists. This work aimed to study the bone mass in children and adolescents with chronic ITP in relation to biochemical markers of bone turnover, cumulative steroid therapy, and the possible modulating effect of vitamin D receptor (VDR) gene polymorphisms. Thirty-six children and adolescents with chronic ITP were recruited from the Hematology Clinic, Children's Hospital, Ain Shams University and the Hematology Clinic of the National Research Centre in Egypt and compared with 43 healthy age- and sex-matched controls. The total cumulative dose of steroids was calculated. Bone markers (serum osteocalcin (OC) and propeptide I precollagen (PICP) and urinary deoxypyridinoline (DPD) excretion), analysis of VDR gene distribution, and dual energy X-ray absorptiometry at lumbar and hip regions were performed for patients and controls. Compared to controls, chronic ITP patients had higher body mass index (BMI) and lower height for age standard deviation score (SDS). Chronic ITP patients had lower levels of OC and C-terminal propeptide of type I procollagen (PICP) and higher urinary DPD excretion, and bone mineral density (BMD) was significantly lower for both spine and hip z-score (<0.001). BMD was inversely correlated with urinary DPD excretion, age, BMI, and cumulative steroid dose. There was significant negative correlation between cumulative oral steroid dose and BMD (r = -0.4, P = 0.01 and r = -0.45, p = 0.001 for spine and hip z-scores, respectively), but the correlation was non-significant in relation to cumulative pulsed steroid therapy. FokI polymorphism was significantly related to BMD for both spine and hip z-score (p = 0.015 and p = 0.008, respectively), but there was no relation between BMD and Bsm1 polymorphism. FokI gene polymorphism may be one of the contributing factors in bone loss in patients on chronic steroid therapy. High cumulative doses of corticosteroids increased bone resorption in young chronic ITP patients. Longitudinal studies are needed to confirm the effect of different steroid protocols on bone turnover. Protocols of therapy of chronic ITP should restrict corticosteroid use in growing children and favor alternative less harmful therapies.

Romiplostim therapy in children with unresponsive chronic immune thrombocytopenia.

Romiplostim, a thrombopoiesis-stimulating peptibody, represents a new therapeutic option in adult refractory chronic immune thrombocytopenia (ITP). This study aimed to assess the short-term efficacy and safety of romiplostim in children with chronic ITP. Eight non-splenectomized patients with chronic ITP refractory to standard lines of medical therapy were recruited from the Pediatric Hematology Unit, Children's Hospital, Ain Shams University, Cairo, Egypt. One patient was initially excluded because of increased bone marrow reticulin (grade 3). Therapy was initiated in seven patients, aged 3.4-15.2 years (median 5.5 years), and the disease duration ranged from 13 months to 7.3 years (median 2.4 years); none were splenectomized. Romiplostim dose was started as 1 µgm/kg/week and the dose escalated by 1 µgm/kg/week according to platelet count. The duration of therapy varied between 1 and 22 weeks (median 12 weeks). Results revealed that four out of the seven patients achieved variable response. Four patients demonstrated rapid increase in platelet count when pulse steroid therapy was added. Most reported adverse events were mild and transient. This case series study reveals variable response rate in children with chronic ITP to romiplostim therapy; addition of steroids especially in emergency bleeding situations could potentiate romiplostim thrombopoietic effect even in patients initially refractory to steroids. Romiplostim safety and efficacy in pediatric ITP needs further long-term studies.

Radionuclide ventriculography detects early anthracycline cardiotoxicity in children with Hodgkin lymphoma.

Serial echocardiography to detect doxorubicin dose-related cardiotoxicity correlates poorly with endomyocardial biopsy-proven cardiotoxicity. To compare radionuclide ventriculography (RVG) and echocardiography for the assessment of left ventricular (LV) function in children with Hodgkin disease (HD) receiving doxorubicin, we studied 39 children with HD before radiotherapy, both early (≤ 2 adriamycin, bleomycin, vinblastine, and dacarbazine cycles) (group A; n=10) and late (≥ 6 adriamycin, bleomycin, vinblastine, and dacarbazine cycles) (group B; n=36) during treatment. Seven children were assessed twice. The patients underwent full clinical assessment, echocardiography, and RVG. In group A, LV ejection fraction (LVEF) was significantly lower when measured by RVG compared with echocardiography (P<0.05). Group B had lower LVEF compared with group A by echocardiography (P=0.09), and by RVG (P=0.000). Paired analysis of children studied early and late showed a significant drop in LVEF by echocardiography (58.7 ± 7.3 vs. 52 ± 52.44%; P=0.04) and RVG (51.4 ± 2.6% vs. 47.2 ± 3.1%; P=0.004). The cumulative dose of doxorubicin inversely correlated with RVG-measured LVEF (r=-0.531; P=0.001). No correlation was found between LVEF measured by RVG and echocardiography (r=0.217; P=0.25). Cardiotoxicity occurred early and at low cumulative doses of doxorubicin in children with HD. RVG was more sensitive than echocardiography in detecting early impairment of LV function. We recommend baseline and serial assessment of LV function by RVG in children with HD receiving doxorubicin.

Health-related quality of life in Egyptian children and adolescents with hemophilia A.

Quality of life (QoL) in hemophilia is an important area in hemophilia outcome assessment. The Haemo-QoL instrument is a set of questionnaires to measure QoL in those children. The objectives of this study was to assess health-related quality of life (HRQoL) in Egyptian hemophilic children and adolescents using an Arabic version of the Haemo-QoL questionnaire. Sixty patients with severe hemophilia A were recruited from 2 hemophilia treating centers in Egypt. Assessment of quality of life was done using the Haemo-QoL questionnaire. The scores of HRQoL were found to be for all dimensions widely above 50. It was highly significant in the 3 dimensions (physical health-family-treatment) in different age groups, but it was impaired in the dimension of "physical health" for 2 groups, and in the dimension of "family" for the oldest group, whereas the youngest group had highly impaired scores concerning the "treatment." The HRQoL in this study was not affected by the presence of factor VIII (FVIII) inhibitors. The QoL in hemophilic patients in Egypt needs strenuous efforts from hemophilia care-integrated teams of pediatric hematologists and psychiatrists in order to properly assess and improve QoL.

Clinicopathological and radiological study of Egyptian ß-thalassemia intermedia and ß-thalassemia major patients: relation to complications and response to therapy.

The clinico epidemiological characteristics, frequency of complications, and response to various therapeutic modalities in 80 Egyptian ß-thalassemia intermedia (ß-TI) patients were compared with 70 ß-thalassemia major (ß-TM) patients. ß-Thalassemia intermedia patients had a higher incidence of left atrium dilatation, right ventricular dilatation and pulmonary hypertension, whereas, ß-TM patients showed a higher incidence of left ventricular (LV) dilatation, restrictive LV filling and impaired LV contractility, with an overall higher incidence of heart disease (p <0.001). Short stature, delayed puberty, osteoporosis, bone fractures, diabetes mellitus and viral hepatitis was frequently observed in ß-TM patients compared with ß-TI patients (p <0.05). Administration of hydroxyurea (HU) alone was associated with significant improvement in hematological parameters and quality of life for ß-TI patients. In conclusion, the risk of complications still burdens the life of Egyptian thalassemia patients and their frequency varies between ß-TI and ß-TM. We provide evidence that calls for the use of HU in ß-TI patients.

Platelet microparticles in immune thrombocytopenic purpura in pediatrics.

Immune thrombocytopenic purpura (ITP) is one of the most common hemorrhagic disorders in childhood. Platelet microparticles (PMPs) arise with platelet activation with procoagulant activity. Elevated PMP levels in adult ITP were reported to be thrombogenic in certain settings. However, their clinical significance in pediatric ITP was not studied. The aims of this study were to assess PMP levels in ITP in children and adolescents, and its correlation with clinical status and bleeding score. The study included 40 ITP patients (20 acute aged 9 +/- 2.19 years and 20 chronic aged 10.8 +/- 4.7 years) randomly selected from the Hematology Clinic, Children's Hospital, Ain Shams University, Cairo, Egypt, and 30 sex- and age-matched healthy controls aged 9 +/- 3.28 years. Patients were subjected to detailed history, assessment of bleeding score, complete hemogram, cytological bone marrow examination, and PMP quantification in peripheral blood by flow cytometry. Acute ITP patients had significant increase in PMPs, PMP/platelet count, and PMP percent compared to controls (P = .002, P < .0001, P < .0001, respectively) and compared to chronic ITP patients (P < .0001, P < .0001, P < .0001, respectively). PMPs were significantly decreased in chronic ITP patients compared to controls (P = .001), but PMP/platelet and PMP percent showed highly significant increase in chronic ITP (P < .0001). No correlation was evident between PMP levels and platelet count in either group (P > .05). Neither higher bleeding score nor thrombotic manifestations were observed in the studied ITP patients with high PMP levels. Elevated PMP levels may be protective against severe bleeding events in pediatric ITP. The role of PMP studies in deciding the management plan of childhood and adolescent ITP needs further evaluation.