Normal values for mean platelet volume (MPV) and platelet distribution width (PDW) have not been firmly established for term and preterm neonates. Cord blood samples from 143 healthy newborns (78 full term and 65 premature) were analyzed with the Coulter counter. Platelet count and MPV were significantly greater (p < 0.05 and p < 0.001, respectively) in term versus preterm infants, while PDW was significantly less in term infants (p < 0.001). Platelet count and MPV correlated with gestational age, and platelet count also correlated with birth weight. There was a significant (p < 0.001) negative correlation of PDW with gestational age and birth weight. These data represent normal reference ranges for neonates and demonstrate significant variation with gestational age. (C) Lippincott-Raven Publishers.

Chemotherapy is an effective mode of therapy for children with histioeytosis, either alone or in conjunction with radiotherapy. This paper summarizes the results of clinical trials with both single-agent and multiple-agent treatment regimens and describes the prognostic variables which must be considered in designing future clinical trials. (C) Lippincott-Raven Publishers.

Sickle cell disease, a disease prevalent among the negroes all over the world, is discussed first from the historical point of view. Its geographical occurrence which is highest in the African subcontinent and lowest in the United States depends on the prevalence of malaria in the environment and intermarriage of races. The sociocultural background of Nigeria is discussed along with its existing health and educational problems. These are related to the profound clinical manifestation of sickle cell disease. Some pitfalls in the diagnosis and manifestation of sickle cell disease are mentioned. The problems to the use of certain drugs are highlighted. In solving some of the problems of sickle cell disease attention should be focused on continuous health education, establishing sickle cell clinics, and research aimed at improving the environment of patients in the underprivileged situations of the world where sickle cell disease poses problems. (C) Lippincott-Raven Publishers.

Two normal appearing infants presented in the newborn period with elevated white blood cell counts and immature blast cells. Initial bone marrow karyotype analysis showed trisomy of chromosome 21 in all metaphases. In both patients blastemia spontaneously resolved and percentage of trisomy 21 cells decreased. One infant required multiple exchange transfusions and pericardotomy. The other patient had undifferentiated blasts and continued to have subtle hematopoietic abnormalities >2 years later. Both children have had normal growth and development. The clinical course of these patients emphasizes the need for aggressive supportive care without use of cytotoxic drugs in phenotypically normal new-borns with blastemia showing trisomy 21. (C) Lippincott-Raven Publishers.

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Advances in the treatment of patients with sickle cell disease have prolonged life span and increased the number of patients surviving into late adulthood. Many patients however, fail to reach their maximum potential because of the debilitating effects of recurrent pain. Our experience in a large pediatric-adult sickle cell program suggests that a comprehensive medical approach, utilizing adequate analgesic therapy and extensive counseling, can significantly reduce the morbidity and hospitalization due to chronic pain. We describe herein our approach to treatment of pain in sickle cell disease and report the results we have obtained by following it. (C) Lippincott-Raven Publishers.

Medulloblastoma comprises approximately 20% of all primary pediatric brain tumors. Despite recent advances, the survival rate for high-risk patients and the morbidity associated with these treatments remains suboptimal. To improve outcomes and decrease morbidity, more targeted therapy is required. One possible target is the Aurora Kinase family. The objective of this study was to evaluate the impact of Aurora Kinase A inhibition in medulloblastoma cell lines.Cell proliferation was measured using an MTS assay after adding an Aurora Kinase inhibitor (C1368) at different concentrations. Cell cycle analysis was carried out by Flow Cytometry using propidium iodide (PI). RNAi experiments were performed using siRNA oligonucleotides. Luciferase experiments were carried out using the Cignal Finder 10 Pathway Reporter Arrays.Inhibition of Aurora Kinase A induces cell death in medulloblastoma cells and lowers the IC50 of other chemotherapeutic agents (etoposide and cisplatin) used in medulloblastoma treatment. Cell arrest at G2/M phase was significantly increased in medulloblastoma cell lines treated with C1368 Sigma at IC30 or transfected siRNA. Inhibition of Aurora Kinase A resulted in decreased activity of pro-proliferative signaling pathways including Wnt, Myc, and RB as measured by luciferase reporter assays.These data indicate that inhibition of Aurora Kinase A inhibits cell growth in medulloblastoma through inhibition of pro-proliferative signaling pathways Wnt, Myc, and RB. Additionally, combining Aurora Kinase A inhibition with other chemotherapeutic agents significantly lowers their IC50, which make it a promising small molecule target for medulloblastoma therapy. Pediatr Blood Cancer. © 2010 Wiley-Liss, Inc.

Survivors of childhood acute myeloid leukemia (AML) face increased risks of chronic disease and secondary malignancies. Substance exposure may compound these risks.Participants were diagnosed with AML at <21 years of age and survived [ge]5 years following diagnosis. All underwent chemotherapy alone or followed by autologous BMT (chemo ± autoBMT) or underwent allogeneic BMT (alloBMT) if an HLA-matched related donor was available. Survivors completed a health questionnaire and a Youth Risk Behavior Survey (YRBS).Of eligible survivors, 117 were [ge]18 years of age and completed a YRBS. Survivors were a mean age of 10 years at diagnosis and 24 years at interview. Of the substance exposures assessed by YRBS, tobacco, alcohol, and marijuana were most common. Twenty-two percent (22%) had smoked cigarettes in the last 30 days. One-quarter (25%) reported binge drinking in the last month. None of these exposures varied by treatment group. Less than 10% of survivors reported cocaine, heroin, or methamphetamine use. Men were more likely to report high substance exposure (P = 0.004). Sadness/suicidality score was associated with cancer-related anxiety (P = 0.006) and multiple health conditions (P = 0.006).This analysis reveals exposure to tobacco, alcohol, and marijuana in young adults with few differences based on treatment received. Survivors with cancer-related anxiety or multiple health conditions were more likely to report sadness/hopelessness. Pediatr Blood Cancer © 2010 Wiley-Liss, Inc.

Clofarabine, a nucleoside analogue for treatment of relapsed leukemia, is 50-60% excreted in urine. Clofarabine has not been studied in patients on hemodialysis. We measured levels in one patient in acute renal failure. Prior to dialysis, 43 hr after a 40 mg/m2 infusion, plasma concentration was 139 ng/ml. One hour after begining hemodialysis, a 20 mg/m2 infusion began. Plasma concentrations were 84.2, 81.1, and 88.0 ng/ml while the dialysis and clofarabine infusion occurred simultaneously. Post-dialysis, while the clofarabine was still infusing, the level was 95.8 ng/ml. Hemodialysis does decrease clofarabine levels, but given its large volume distribution, hemodialysis may not be effective for clofarabine overdose. Pediatr Blood Cancer. © 2010 Wiley-Liss, Inc.

A potential long-term complication of central venous catheter (CVC)-related deep vein thrombosis (DVT), both symptomatic and asymptomatic, is development of post-thrombotic syndrome (PTS) characterized by persistent pain, swelling, and skin changes. Signs and symptoms of PTS were reported after CVC removal. The aim of this study was to assess the risk factors for development of PTS in childhood cancer survivors.Children followed at the after cancer follow-up clinic were enrolled. The patients were screened for PTS using Kuhle's PTS pediatric score. Patient's records were retrospectively reviewed for clinical and CVC-related data.Fifty-one children were enrolled at a median of 2.3 (range 0.33-7.5) years after removal of their CVC. The median age of the children the time of treatment was 6.5 (range 0.25-18) years. Mild PTS was present in 20 children (39%, 95% CI 26-54%). Pain symptoms were reported in five children (9.5%, 95% CI 3.3-21.4%). Higher rate of PTS was found in children with history of CVC occlusion. The odd ratio (95% CI) for PTS in children with history of occlusion was 3.7 (95% CI 1.1-12.5%) (P = 0.029). The occurrence of PTS was not associated with age at the time of treatment, time from CVC removal, duration of CVC, and history of infection.Screening cancer survivors for PTS after CVC removal should be integrated to the after cancer follow-up clinic. Obstruction of CVC may indicate for asymptomatic DVT. Whether thromboprophylaxis and/or prevention of CVC occlusion can decrease the rate of PTS needs to be studied. Pediatr Blood Cancer. © 2010 Wiley-Liss, Inc.

Individuals with sickle cell disease (SCD) demonstrate an increased susceptibility to invasive bacterial infections (IBI). The most common organisms causing IBI are Streptococcus pneumoniae, nontyphi Salmonella species and Haemophilus influenzae type b (Hib). IBI are the most common causes of death in children below 5 years of age with SCD. Increased susceptibility to IBI is because of several factors including dysfunctional antibody production and opsonophagocytosis as well as defective splenic clearance. Early diagnosis of Hib and pneumococcal infections combined with antibiotic prophylaxis and immunization programs, could lead to significant improvements in mortality, especially in Africa. Pediatr Blood Cancer. © 2010 Wiley-Liss, Inc.

Defects in apoptosis signaling have been considered to be responsible for treatment failure in many types of cancer, although with controversial results. The objective of the present study was to assess the expression profile of key apoptosis-related genes in terms of clinical and biological variables and of the survival of children with acute lymphoblastic leukemia (ALL).The levels of mRNA expression of the apoptosis-related genes CASP3, CASP8, CASP9, FAS, and BCL2 were analyzed by quantitative real-time PCR in consecutive samples from 139 consecutive children with ALL at diagnosis treated by the Brazilian protocol (GBTLI-ALL 99). Gene expression levels and clinical and biological features were compared by the Mann-Whitney test. Event-free survival (EFS) was calculated by Kaplan-Meier plots and log-rank test.A significant correlation was detected between CASP3, CASP8, CASP9, and FAS expression levels (P < 0.01) in ALL samples. Higher levels of BCL2 were significantly associated with white blood cell (WBC) count <50,000/mm3 at diagnosis (P = 0.01) and low risk group classification (P = 0.008). Lower expression levels of CASP3, CASP8 and FAS gene were associated with a poor response at day 7 according the GBTLI-ALL 99 protocol (P = 0.03, P = 0.02 and P = 0.008, respectively). There was a relationship between FAS gene expression lower than the 75th percentile and lower 5-year EFS (P = 0.02).These findings suggest an association between lower expression levels of the pro-apoptotic genes and a poor response to induction therapy at day 7 and prognosis in childhood ALL. Pediatr Blood Cancer. © 2010 Wiley-Liss, Inc.

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MDM2 SNP309, characterised by a T-to-G substitution in the MDM2 promoter, is associated with higher gene expression compared to wild type and was recently found to be a negative prognostic factor for patients with stage 4 neuroblastoma (NB), but not for children with localised disease. This polymorphism was not associated with any clinical or genetic tumour characteristics, including MYCN amplification and 1p chromosome deletion.To better define the involvement of MDM2 SNP309 in NB, we explored its association with the main biochemical tumour markers, namely urinary concentrations of vanillyl mandelic acid (VMA) and homovanillic acid (HVA) and blood concentrations of ferritin and lactate dehydrogenase (LDH). A cohort of 497 NB children, enrolled in the Italian Neuroblastoma Registry between January 1985 and December 2005 and previously investigated for the prognostic role of MDM2 SNP309, was considered for this study.VMA and HVA concentrations as well as HVA/VMA ratio were not affected by the MDM2 SNP309 genotype. Ferritin and LDH concentrations were significantly lower in TT than in TG/GG only in patients with stage 4 disease (P = 0.007 and 0.015, respectively). No association emerged in patients with localised disease. These findings were not affected by confounding from clinical or biological characteristics.The association between MDM2 SNP309 and both ferritin and LDH in patients with stage 4 disease confirms the prognostic role of this polymorphism. The results suggest that the MDM2 SNP309 genotype can impact on tumour responses to hypoxia and might play an important role in the alteration of energetic metabolism in NB cells. Pediatr Blood Cancer. © 2010 Wiley-Liss, Inc.