Genetic polymorphism of vitamin D receptors and plasminogen activator inhibitor-1 and osteonecrosis risk in childhood acute lymphoblastic leukemia.

BACKGROUND: Osteonecrosis (ON) is one of the major therapy-related complications in childhood acute lymphoblastic leukemia (ALL). The purpose of the current study is to assess the frequency of ON in children with ALL and to detect whether polymorphisms in vitamin D receptor gene (VDR) and plasminogen activator inhibitor-1 (PAI-1) gene can affect the risk of ON. PATIENTS AND METHODS: Nighty-six ALL children were enrolled. Serum 25-hydroxyvitamin D 25(OH)D levels were performed in addition to the detection of polymorphisms in PAI-1and VDR genes by polymerase chain reaction. RESULTS: Ten out of 96 patients had ON (four males and six females aged above 10 years) and had an insufficient level of 25(OH)D. Fifty-two percent of patients had PAI-1 GG genotype while 48% had PAI-1 GA genotype. PAI-1 polymorphism was detected in 60% of all ON cases. The frequencies of VDR genotypes were CT (56.3%), CC (39.6%), and TT (4.2%). Osteonecrosis was found in eight patients with CC genotype and in two patients with CT genotype. CONCLUSION: Osteonecrosis can develop early during the therapy of ALL. Older age and insufficient level of 25(OH)D were considered important risk factor for the development of osteonecrosis. PAT-1 and VDR gene polymorphism may be a genetic risk factor in its pathogenesis.

A Cross-sectional Study of Two Chemotherapy Protocols on Long Term Neurocognitive Functions in Egyptian Children Surviving Acute Lymphoblastic Leukemia.

INTRODUCTION: Subtle neurocognitive deficits have been recently observed in Acute Lymphoblastic Leukemia (ALL) survivors. AIM: We aim to assess the neurocognitive functions of ALL survivors who had been treated with chemotherapy only using two different protocols, and to identify treatment-related risk factors. PATIENTS AND METHODS: We carried a multicenter study involving 3 pediatric oncology centers on 100 children who were treated for ALL. Fifty patients were treated by the modified Children's Cancer Group (CCG) 1991 protocol with low dose methotrexate and 50 children were treated by Total XV protocol with high dose methotrexate. Fifty healthy children were included as a control group. Psychometric assessment using Arabic version of Wechsler intelligence scale for children (WISC III) was performed for all patients and controls. RESULTS: Patients had significantly lower mean full scale IQ, performance IQ and verbal IQ than controls. Patients ≤ 5 years at diagnosis had significantly lower mean full scale IQ and performance IQ than patients>5 years at diagnosis, while the verbal IQ showed no significant difference between both age groups. Female patients had significantly lower mean full scale IQ, performance IQ and verbal IQthan males. Patients who received Total XV protocol with high dose methotrexate had significantly lower mean full scale IQ, performance IQ and verbal IQ than patients who received modified CCG 1991 protocol with low dose methotrexate. CONCLUSIONS: CNS directed chemotherapy might appear to affect neurocognitive functions in children with ALL, which is more significant in young children at diagnosis, in girls and in those receiving high dose methotrexate.

Screening of renal dysfunction among Burkitt lymphoma survivors by novel markers.

BACKGROUND: Burkitt lymphoma (BL) represents the most common pathological type of non-Hodgkin lymphoma in our region. Recently, high success rates have been achieved in BL treatment. Little is known about long-term renal dysfunction in this vulnerable group. In the present study, we tried to detect early chronic kidney diseases (CKD) among BL survivors by using novel screening modalities. PATIENTS AND METHODS: we investigated 53 children (aged 10 ± 2.8 years, 34 boys) who successfully treated for Burkitt lymphoma, based on LMB96 protocol, as "patient group" and 30 children as control. All eligible participants were subjected to history taking, physical assessment, and routine laboratory investigations including urine analysis, serum creatinine. Estimated glomerular filtration rates using new Schwartz formula (GFRCKD) were calculated and chronic kidney disease prevalence was diagnosed accordingly. Also, serum Cystatin-C (Cys-C) and neutrophil-gelatinase-associated Lipocalin (NGAL) were determined as novel markers aiming at early and accurate detection of CKD in BL survivors. RESULTS: After 18.3 ± 5.2 months of BL cytotoxic therapy completion, almost one fifth of asymptomatic BL survivors showed evidence of subclinical CKD when estimated GFRCKD (16.9%), serum Cystatin-C (15%) and serum neutrophil-gelatinase-associated Lipocalin (18.8%) were used for kidney function monitoring. This prevalence was four to fivefolds higher than that detected by routine serum creatinine screening (3.7%). Significant persistent albuminuria was diagnosed at 4/53 (7.5.3%) of BL survivors and asymptomatic hypertension was reported in 1/53 (1.9%) of them compared to none of the controls. Positive correlation could be displayed between serum Cys-C and serum NGAL. Conversely, negative correlations between both of them and estimated GFRCKD were documented. CONCLUSION: Novel modalities such new Schwartz formula (GFRCKD) estimation, serum Cys-C, and serum NGAL assessment should be incorporated in the routine follow-up screening for CKD among BL survivors for accurate diagnosis of such detrimental morbidity.

Cadmium status among pediatric cancer patients in Egypt.

Cadmium (Cd) is a toxic, nonessential, and bio-accumulating heavy metal widely used in industry. Several studies have suggested a positive association between Cd exposure and risks of several cancers. However, data from general population, especially children are sparse.In the current cross-sectional case-control study, we aimed to assess the association between Cd exposure, as expressed by Cd body status (blood, urine, scalp hair, and nails) and cancer among Egyptian children. Three hundred and fifty pediatric cancer cases aged 3 to 14-years old were enrolled in our study. Their body Cd levels were evaluated using Atomic Absorption Spectrophometer and were compared with Cd levels of 350 healthy children.Significantly higher Cd levels (blood, urine, scalp hair, and nails) were documented in cancer cases when compared with control (P < 0.001). Such difference was still detected when comparing each malignant type separately, with controls. Tobacco smoke exposure, rural residence, and low socioeconomic status were reported more frequently among cases than comparisons.Positive association between Cd exposure and pediatric malignancy may be present.

Hodgkin lymphoma in childhood: clinicopathological features and therapy outcome at 2 centers from a developing country.

Hodgkin lymphoma (HL) accounts for 5% to 6% of all childhood cancer. It displays characteristic epidemiological, clinical, and pathological features according to various geographic areas. We aimed to assess the epidemiological aspects, clinicopathological features, and treatment outcome of pediatric HL treated at 2 Egyptian centers: Zagazig University Pediatric Oncology Unit and Benha Special Hospital Pediatric Oncology Unit. We carried a cross-sectional retrospective study by reviewing medical records for all patients admitted with the diagnosis of HL over 8 years in 2 oncology units during the period from January 2004 to January 2012. Age of the patients at presentation ranged from 3 to 14 years (median 6 years) and male: female ratio 1.7:1. Lymphadenopathy was the most common presentation (96.6%). Mixed cellularity subtype was dominant (50.8%), followed by nodular sclerosis (28.9%), lymphocyte-rich (18.6%) with lymphocyte depletion being the least dominant (1.7%). More than half of patients (55.9 %) had advanced disease (Ann Arbor stage III/IV disease). The duration of follow-up ranged from 5 to 87 months (mean 39.8 ±â€Š24.1 months). The 5-year overall survival and event-free survival for patients were 96.6% and 84.7% respectively. In Egypt, HL occurs in young age group, with a higher incidence of mixed cellularity subtype and advanced disease. None of the clinical, epidemiological, or pathological characteristics had a significant association with the overall survival. The outcomes of HL in our 2 centers were satisfactory approaching the international percentage.

Disease patterns of pediatric non-Hodgkin lymphoma: A study from a developing area in Egypt.

Non-Hodgkin lymphoma (NHL) accounts for 8-10% of all childhood cancers. NHL collectively represents various lymphoid malignancies with diverse clinicopathological and biological characteristics. In this study, we aimed to describe the epidemiological and clinicopathological characteristics and treatment outcomes of pediatric NHL patients treated at the Pediatric Oncology Unit of Zagazig University Hospital and the Benha Specialized Pediatric Hospital. We conducted a cross-sectional retrospective study by reviewing the medical records of 142 patients admitted with a diagnosis of NHL over a period of 8 years (February, 2004 to February, 2012) in these two Oncology Units. The age at presentation ranged between 2 and 15 years, with a mean ± standard deviation (SD) of 6.1±2.8 years and a male:female ratio of 1.7:1. Abdominal involvement was the most common presentation (73.2%). Burkitt's lymphoma (BL) was the most common NHL subtype (69%), followed by lymphoblastic lymphoma, diffuse large B-cell lymphoma and anaplastic large-cell lymphoma, accounting for 18.3, 10.6 and 2.1% of the cases, respectively. The majority of the patients (88.7%) had been diagnosed with advanced disease (Murphy stage III/IV). Complete remission was achieved in 120 cases (84.5%). A total of 16 patients (11.3%) succumbed to the disease during the first few months and 6 patients (4.2%) remained alive following relapse. The mean follow-up duration ± SD was 34.6±25.1 months (range, 3-84 months). The 5-year overall survival (OS) and event-free survival (EFS) rates were 88.7 and 85.1%, respectively. None of the clinical, epidemiological or pathological variables exhibited a statistically significant association with the OS or EFS. In conclusion, NHL occurs at a younger age, with a higher incidence of BL and advanced-stage disease. The outcome of NHL in our two centers was satisfactory, approaching the international rates.