Rasha El-Ashry

Vitamin E and N-Acetylcysteine as Antioxidant Adjuvant Therapy in Children with Acute Lymphoblastic Leukemia

Although cancer therapies have experienced great success nowadays, yet the associated toxic response and free radicals formation have resulted in significant number of treatment-induced deaths rather than disease-induced fatalities. Complications of chemotherapy have forced physicians to study antioxidant use as adjunctive treatment in cancer. This study aimed to evaluate the antioxidant role of vitamin E and N-acetyl cysteine (NAC) in overcoming treatment-induced toxicity in acute lymphoblastic leukaemia (ALL) during the intensive period of chemo-/radiotherapy, almost the first two months of treatment. Forty children newly diagnosed with ALL were enrolled in this study. Twenty children (group I) have taken vitamin E and NAC supplementations with chemotherapy and the other twenty children (group II) have not taken any adjuvant antioxidant therapy. They were evaluated clinically for the occurrence of complications and by the laboratory parameters (blood levels of glutathione peroxidase (Glu.PX) antioxidant enzyme, malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), liver enzymes, and bone marrow picture). Results revealed reduced chemotherapy and radiotherapy toxicity as evidenced by decreasing level of MDA, increasing level of Glu.Px and decreased occurrence of toxic hepatitis, haematological complications, and need for blood and platelet transfusions in group I compared to group II. We can conclude that vitamin E and NAC have been shown to be effective as antioxidant adjuvant therapy in children with ALL to reduce chemo-/radiotherapy-related toxicities during the initial period of treatment.

Nosocomial infections and fever of unknown origin in pediatric hematology/oncology unit: a retrospective annual study

BackgroundPediatric hematology/oncology patients are faced with an increased risk of nosocomial infections (NIs) that vary in different populations and different institutions with considerable morbidity and mortality. This study was undertaken to assess the frequency and patterns of NIs in 1564 pediatric patients and to determine the prevalence of causative organisms and their antimicrobial sensitivity.MethodsA retrospective analysis was made in the patients admitted between January 2007 and January 2008 to the pediatric hematoloy/oncology unit of Mansoura University, Egypt. The 1564 patients showed 2084 admissions and 27 092 inpatient days. The Centers for Disease Control and Prevention criteria were used as a standard definition for NI.ResultsThe overall rate of NIs in all patients and neutropenic patients was 8.6 and 25.3 per 1000 patient-days respectively. The frequent sites of NIs were blood stream (42.7%), the respiratory system (25.3%), the urinary system (22.2%) and the central nervous system (9.8%), whereas nosocomial fever of unknown origin constituted 52.9% of cases. The incidence of NIs was significantly higher during neutropenic days (P<0.001). Gram-positive organisms represented 64.5% of pathogens (Staphylococci 71.5%, Streptococci 16%, and pneumococci 7%), and Gram-negative organisms represented 30% (E. coli 48.6%, Klebsiella 15.7%, Pseudomonas 35.7%, and C. albicans 5.5%). Positive cultures were more frequent in summer (July to September). Susceptibility of isolated organisms was relatively low (cefoperazone/sulbactam 49.9%, amikacin 35.9%, imipenem/cilastin 34.4%, cefoperazone 33.6%, and vancomycin 36.5%). Methicillin-resistant S. aureus, extended spectrum beta lactamase and vancomycin resistant enterococci represented 30%, 45% and 75% of isolated S. aureus, Gram-negative organisms and Enterococci, respectively.ConclusionsBlood stream infection and fever of unknown origin are the most common nosocomial infections in pediatric hematology/oncology patients with a higher risk during neutropenic days. Isolated organisms are multi-drug resistant, predominantly Gram-positive pathogens with a high incidence of methicillin-resistant S. aureus, extended spectrum beta lactamase and vancomycin resistant enterococci organisms.

Expression of lung resistance protein and multidrug resistance-related protein (MRP1) in pediatric acute lymphoblastic leukemia

Multidrug resistance (MDR) is a phenomenon by which cells become resistant to unrelated chemotherapeutic agents. The prognostic value that lung resistance protein (LRP) and multidrug resistance-related protein 1 (MRP1) have in the setting of pediatric acute lymphoblastic leukemia (ALL) is controversial. The aim of this study was to investigate the expression of LRP and MRP1 and effect on clinical outcome and prognosis. The mRNA expression of LRP and MRP1 were analyzed in leukemic blasts of 34 pediatric ALL patients. LRP and MRP1 mRNA expression were detected in 41.2% and 35.3%, respectively. Eleven (91.7%) of 12 patients without LRP achieved CR compared with 9 (50.0%) of 18 with LRP expression. Similarly, 11 (100%) of 11 patients without MRP1 expression achieved CR compared with 9 (47.4%) of 19 with MRP1 expression and higher LRP expression rate or MRP1 expression rate was present in patients with relapse than MDR genes negative patients. The expression of either of two genes was associated with poorer 2-year survival. Also, patients expressing both genes had poorer outcomes and had worse 2-year survival. We suggest that MDR expression affects complete remission and survival rates in ALL patients. Thus, diagnosis appears to provide prognostic information for pediatric ALL.

Bone mineral density in newly diagnosed children with neuroblastoma

Neuroblastoma is the second most common extracranial malignant tumor of childhood and the most common solid tumor of infancy which is characterized by bone metastasis. Previous reports on bone mineral density (BMD) in patients with leukemia and solid malignancies concentrate on long‐term survivors and on the effect of chemotherapeutic agents and irradiation. Also, evaluation of BMD in neuroblastoma was reported in few studies which were conducted upon adult survivors of childhood cancer. Previous studies on both acute leukemia and lymphoma patients suggested that the disease process itself played a role in decrease BMD.

Frequency and prognostic significance of murine double minute protein-2 overexpression and p53 gene mutations in childhood acute lymphoblastic leukemia

Abstract Aim: Determination of frequency and prognostic significance of murine double minute protein-2 (MDM-2) over expression and its association with p53 status in children with acute lymphoblastic leukemia (ALL). Methods: MDM-2 expression by flow cytometry and p53 gene status by PCR were determined in peripheral blood or bone marrow of 46 ALL children (at initial diagnosis) and control group. Results: MDM-2 was significantly overexpressed in 15 patients (32·6%). p53 mutation was detected in six out of 46 patients at initial diagnosis, three of them were out of 29 cases achieving complete remission (CR) and the other three cases were out of 17 of relapsed patients, which is significantly higher than CR group (P<0·05). Positive correlation was found between the MDM-2 overexpression and initial WBCs count, peripheral blast cell count and presence of CNS blasts (P<0·05, <0·05 and <0·05 respectively). Conclusion: MDM-2 is overexpressed in a significant number of childhood ALL, and more often observed in the poor outcome group and its frequency is not related to p53 status. Measurement of MDM-2 as a bad prognostic marker even in cases with non-mutant p53 is very important. Moreover, MDM-2 may be a potential molecular target for production of new cancer therapy.

Sickle Cell Disease (SCD)

Sickle cell anemia (SCA) is a disease that is caused by the formation of an abnormal hemoglobin type, which can bind with other abnormal hemoglobin molecules within the red blood cells (RBCs) to cause rigid distortion of the cell. This distortion prevents the cell from passing through small blood vessels; leading to occlusion of vascular beds, followed by tissue ischemia and infarction. Infarction is frequent all over the body in patients with SCA, leading to the acute pain crisis. Over time, such insults re‐ sult in medullary bone infarcts and epiphyseal osteonecrosis. In the brain, cognitive impairment and functional neurologic deficits may occur due to white matter and gray matter infarcts. Infarction may also affect the lungs increasing susceptibility to pneumonia. The liver, spleen, and kidney may show infarction as well. Sequestration crisis is an unusual life-threatening complication of SCA, in which a significant amount of blood is sequestered in an organ (usually the spleen), leading to collapse. Lastly, since the RBCs are abnormal, they are destroyed, resulting in a hemolytic ane‐ mia. However, the ischemic complications in patients with SCA disease far exceed the anemia in clinical significance.

Comparative study of two mechlorethamine, vincristine, procarbazine, and prednisone derived chemotherapeutic protocols for the management of pediatric Hodgkin lymphoma (HL): single-center 5-year experience

We aimed for the comparison of two protocols (OAP and COMP) as chemotherapy treatment in children with Hodgkin lymphoma (HL). A total of 119 children newly diagnosed with HD were divided to receive either the anthracycline-based OAP protocol or the alkylating-agent-based COMP protocol. Sixty patients received the OAP protocol and 59 patients received the COMP protocol. Complete response was achieved for 81.4% of patients treated with the COMP protocol versus 53.3% for those who received the OAP treatment. Toxic hepatitis or liver cell failure was recorded in 5% of patients treated with the COMP protocol. Complications were more frequent in those treated with the OAP protocol, as 6.8% developed heart failure and 20% showed toxic hepatitis or liver cell failure. The relapse rate was almost equal in both treatment arms. Patients treated with the COMP protocol achieved a better response and less toxicity but with similar survival to those given the OAP protocol.

Papillary thyroid carcinoma presenting with upper respiratory tract obstruction and pulmonary metastases

BackgroundThyroid cancer is rare in children especially before the age of 10 years. Upper airway obstruction and pulmonary infiltration are rare manifestations of such tumor.MethodsAn 8-year-old school girl was admitted to Mansoura University Children’s Hospital for a papillary thyroid carcinoma manifested by severe upper respiratory tract obstruction. CT scan of the chest revealed multiple miliary shadows in both lungs.ResultsTotal thyroidectomy was performed and pathological examination confirmed the diagnosis of papillary carcinoma of the thyroid gland. The patient received ablative dose of Iodine 131 and replacement therapy of L-thyroxine.ConclusionThyroid cancer, although rare, should be considered for differential diagnosis of upper airway obstruction and pulmonary metastases.

Primary hepatic non-Hodgkin lymphoma presenting as acute hepatitis in a 2-year-old male.

Hematol Oncol Stem Cell Ther 2(1) First Quarter 2009 hemoncstem.edmgr.com 299 Non-Hodgkin lymphoma (NHL) is the third most common childhood malignancy with an overall incidence of 10.5 per million.1 Its incidence is higher in the Middle East as a result of an increased incidence of endemic Burkitt lymphoma. It is usually restricted to lymphoid tissue such as lymph modes, Peyer patches, and the spleen.1 Primary hepatic NHL is very rare in the pediatric age range. It may be asymptomatic and discovered accidentally or present with non-specific symptoms like abdominal discomfort and/or pain with some constitutional manifestation.2 We report a rare case of primary hepatic NHL presenting as acute hepatitis in a child aged 2.5 years who responded to chemotherapy.

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

Abstract 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.