Hydroxyurea Use Associated with Nonverbal and Executive Skills in Sickle Cell Anemia.

OBJECTIVE: Hydroxyurea (HU) is used in children with sickle cell disease (SCD) to increase fetal hemoglobin (HF), contributing to a decrease in physical symptoms and potential protection against cerebral microvasculopathy. There has been minimal investigation into the association between HU use and cognition in this population. This study examined the relationship between HU status and cognition in children with SCD. METHODS: Thirty-seven children with SCD HbSS or HbS/ß0 thalassaemia (sickle cell anemia; SCA) ages 4:0-11 years with no history of overt stroke or chronic transfusion completed a neuropsychological test battery. Other medical, laboratory, and demographic data were obtained. Neuropsychological function across 3 domains (verbal, nonverbal, and attention/executive) was compared for children on HU (n = 9) to those not taking HU (n = 28). RESULTS: Children on HU performed significantly better than children not taking HU on standardized measures of attention/executive functioning and nonverbal skills. Performance on verbal measures was similar between groups. CONCLUSIONS: These results suggest that treatment with HU may not only reduce physical symptoms, but may also provide potential benefit to cognition in children with SCA, particularly in regard to attention/executive functioning and nonverbal skills. Replication with larger samples and longitudinal studies are warranted.

Changes in Blood Profile from Steady State in Patients with Sickle Cell Anemia Admitted for Vaso-occlusive Crisis and Acute Chest Syndrome.

Close to half of all patients with sickle cell disease (SCD) will have at least one episode of acute chest syndrome (ACS) during their lifetime. Multiple cells and molecules involved with the inflammatory cascade play a role in the development of ACS. We found that patients with SCD who developed ACS as a complication of a vaso-occlusive crisis (VOC) had a significant increase in leukocytes and decrease in platelets from their steady state when compared with a separate admission for VOC without ACS development. No significant change from steady state hemoglobin or reticulocyte count was noted between the two admissions. These results indicate that trending laboratory markers may be useful to predict patients at risk for ACS development.

Laboratory Biomarkers, Cerebral Blood Flow Velocity, and Intellectual Function in Children with Sickle Cell Disease.

OBJECTIVE: The aim of this preliminary study was to describe putative markers of cerebral vasculopathy and investigate relationships among these markers, demographic factors, and cognitive function in a young sample of neurologically normal children with SCD. Study Design. Thirty-eight children with homozygous HbS, aged 4-11 years, were included. Estimated IQ and markers of coagulation and endothelial activation, hemolysis, and inflammation, as well as transcranial Doppler velocities, hydroxyurea use, and demographic information were obtained. RESULTS: Using multiple regression analyses, there were few significant independent associations between biomarkers or blood flow velocity and estimated IQ. Lactic dehydrogenase (LDH) independently predicted cognitive function, but blood flow velocity did not mediate this relationship. Maternal education, patient age, and hydroxyurea status were independent predictors of cognition. Given the small sample size, a LASSO statistical model was employed to further identify potential predictors of IQ, which identified LDH, absolute neutrophil count (ANC), platelet count, thrombin-antithrombin (TAT), tissue factor (TF), maternal education, age, and hydroxyurea as potential predictors of cognition. CONCLUSIONS: In addition to effects of age and maternal education, some vasculopathic markers are associated with cognitive function in young children with SCD, and these relationships do not appear to be mediated through blood flow velocity. Although the lack of association among certain variables was not as predicted, results provide support for further research regarding the influence of vasculopathic markers on cognitive function in children with SCD without stroke, especially intravascular hemolysis and coagulation/endothelial activation, and a possible role for HU treatment in preventing or reversing cognitive decline.

Relationship of Omega-3 fatty acids DHA and EPA with the inflammatory biomarker hs-CRP in children with sickle cell anemia.

BACKGROUND: Inflammation and vaso-occlusion play key roles in Sickle Cell Disease (SCD) pathophysiology. Lipoxygenase products of the omega-3 fatty acids (O3FAs), docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids, are potent anti-inflammatory mediators modulating pain. O3FAs decrease episodes of vaso-occlusion in SCD. METHODS: We assessed erythrocyte fatty acid composition in two major cell membrane phospholipids, phosphatidylcholine and phosphatidylethanolamine, in children with SCD HbSS-disease (n = 38) and age/race-matched HbAA-controls (n = 18). Ratio of pro-inflammatory arachidonic acid (AA) to anti-inflammatory DHA and EPA (FA-Ratio), and its relationship to hs-CRP were evaluated. RESULTS: FA-Ratios were increased in both phosphatidylcholine and phosphatidylethanolamine in HbSS compared to controls. Correlations were noted in HbSS subjects between hs-CRP and FA-Ratios (p = 0.011). FA-Ratios increased with age (p = 0.0007) due to an increase in pro-inflammatory AA with a concomitant decrease in anti-inflammatory DHA. CONCLUSIONS: Findings demonstrate relative deficiencies in HbSS of the anti-inflammatory precursor fatty acids DHA and EPA, which correlates positively with hs-CRP.

Body Mass Index and the Association With Vaso-occlusive Crises in Pediatric Sickle Cell Disease.

BACKGROUND: Children with sickle cell disease (SCD) historically have been underweight and have poor overall growth. Recent studies have demonstrated a trend toward obesity in pediatric SCD populations. MATERIALS AND METHODS: Through retrospective chart review of patients with SCD followed at our center, we collected patient's data, including body mass index (BMI), weight percentiles, sickle cell genotype, baseline hemoglobin, medical and psychiatric comorbidities, 25-hydroxy vitamin D level, treatment with hydroxyurea, and chronic transfusions. We identified hospitalizations to St. Christopher's Hospital for vaso-occlusive crisis (VOC) and duration of hospitalization and intravenous opioid use were recorded. Student t test, Mann-Whitney U test, and analysis of variance were used to examine associations between variables and frequency and duration of hospitalizations for VOC. RESULTS: Among 328 patients with SCD, overweight and obese children constituted 19% of hospitalized and nonhospitalized patients. BMI status did not influence frequency (P=0.90) or duration of hospitalization (P=0.65) for VOC. Obesity was more associated with HbSC than HbSS (P=0.025) genotype. CONCLUSIONS: Our study did not demonstrate an association between extremes of BMI of patients and hospitalization for VOC. Considering current trend toward obesity, further prospective and interventional research are required to define the effects of extremes of BMI on pain crises in SCD.

Treatment of refractory Langerhans cell histiocytosis (LCH) with a combination of 2-chlorodeoxyadenosine and cytosine arabinoside.

The combination of 2-chlorodeoxyadenosine (2-CDA) and cytosine arabinoside (Ara-C) has been shown to be effective in children with refractory Langerhans cell histiocytosis (LCH). We have treated 5 patients with recurrent LCH with 2-CDA/Ara-C chemotherapy and closely followed immune and hematopoietic function. These patients display a decline in the absolute CD4, CD8, and natural killer cell number, decrease in the CD4/CD8 ratio. Septic events, including pneumocystis infection were present after most of the treatment courses (15/21). These data suggest that 2-CDA /Ara-C, should be considered in resistant and relapsed pediatric patients with LCH with high-risk multiorgan involvement. Consequent profound prolonged combined immune deficiency and myelosupression should be anticipated.

Transient myeloproliferative disorder in neonates with and without Down syndrome: a tale of 2 syndromes.

Transient myeloproliferative disorder (TMD) in newborns with Down syndrome (DS) has been well described. We report 4 newborns, 2 with DS and 2 without DS, who developed TMD. One newborn with DS developed multiorgan failure and died despite treatment with low-dose cytarabine. In 3 newborns, the TMD resolved spontaneously. Two of these patients, 1 with and 1 without DS developed leukemia on subsequent follow-up and were treated successfully. We reviewed the clinical and laboratory data on 14 non-DS infants with TMD reported in the literature. According to limited data, these patients are more likely to develop leukemia than DS patients, however their outcome is better.

Intracerebral presentation of Hodgkin disease mimicking meningioma in a young woman: case presentation with literature review.

Intracranial involvement of the Hodgkin disease (HD) is a rare entity. Until now, 9 cases of initial presentation of the HD as a brain tumor with appropriate morphologic and histochemical confirmation were reported. Of the 9 patients, 6 had isolated primary intracranial HD and 3 patients after further investigation were found to have extracranial involvement. Seven patients had nodular sclerosing histology, 1 had mixed cellularity, and in 1 case histology was not reported. We describe a patient with systemic nodular sclerosing HD, who initially presented with a brain mass mimicking meningioma and was found to have disseminated lymphadenopathy and bone involvement.