OBJECTIVE: To examine the 1-month effects of a pain coping skills intervention in children with sickle cell disease (SCD). METHODS: Forty-six African American children (8-17 years old) were randomly assigned to either a coping skills condition or a standard care control condition. Children were asked to practice daily with audiotaped instructions of skills (e.g., relaxation, imagery). RESULTS: Multivariate analyses of summary measures indicated that children in the coping intervention (versus control group) reported a significantly more active approach to managing pain. Multilevel random effects models applied to daily diary data indicated that on pain days when children practiced their strategies, they had fewer health care contacts, fewer school absences, and less interference with household activities than on days when they did not practice. CONCLUSIONS: Brief training in coping skills followed by minimal therapist contact may lead to a range of benefits when children practice with their skills on a consistent basis.

Adaptation, Psychological↗

PubMedDate not supplied

Trilineage hematopoietic toxicity associated with valproic acid therapy.

PURPOSE: Sodium valproate is commonly used as an anticonvulsant for patients with refractory epilepsy. Hematopoietic toxicity involving platelets or erythrocytes has been previously described, as well as a few cases of generalized bone marrow suppression. PATIENTS AND METHODS: We report an infant receiving sodium valproate who developed severe anemia and thrombocytopenia, numerous circulating immature myeloid cells, and a coagulopathy. Bone marrow aspirate revealed approximately 40% abnormal promyelocytes, and the initial clinical and pathologic interpretation was consistent with the diagnosis of acute promyelocytic leukemia. RESULTS: Antineoplastic therapy was withheld while valproate was weaned. All hematopoietic abnormalities resolved after valproate therapy was discontinued. CONCLUSION: This report expands the clinical spectrum of hematopoietic toxicity associated with sodium valproate. Drug toxicity should be considered in any patient on valproate who develops hematopoietic abnormalities.

Cell Lineage↗

PubMedDate not supplied

Clinical significance of the antinuclear antibody test in selected children with idiopathic thrombocytopenic purpura.

PURPOSE: To determine the clinical significance of the antinuclear antibody (ANA) test in selected children with idiopathic thrombocytopenic purpura (ITP). METHODS: The study was conducted through retrospective chart review and long-term follow-up by telephone interview. RESULTS: Of 87 children with ITP who had an ANA performed, 25 had a positive titer (median = 1:160, range: 1:40 to 1:2,560). Children with a positive ANA were more likely to be older girls who developed chronic ITP, but there was no correlation with family history of autoimmune disease, initial hemoglobin concentration, or initial platelet count. With an average follow-up of more than 5 years, more children with a positive ANA developed further autoimmune symptoms than those with a negative ANA (36% vs. 0%, p < 0.001). Nine children with a positive ANA developed additional autoimmune symptoms, including five with clinical criteria sufficient for the diagnosis of systemic lupus erythematosus (SLE). Autoantibodies to dsDNA were more prevalent in the children with progression of autoimmune symptoms (57% vs. 0%, p = 0.04). The presence of any autoantibody in addition to the ANA, including dsDNA, SS-A/Ro, SS-B/La, Smith Antigen (Sm), nuclear ribonucleoprotein (nRNP), or cardiolipin was more common in children who had further autoimmune symptoms (75% vs. 0%, p = 0.003). CONCLUSIONS: The ANA is a useful screening test in a subset of children with ITP, especially older girls with chronic ITP, who are at risk for the development of generalized autoimmune disease. Children with ITP and a positive ANA should receive careful follow-up.

Adolescent↗

PubMedDate not supplied

Physiologic decline in fetal hemoglobin parameters in infants with sickle cell disease: implications for pharmacological intervention.

PURPOSE: Fetal hemoglobin (HbF) is an important determinant in the clinical severity of patients with sickle cell disease. The physiologic decline in HbF parameters in a cohort of infants with sickle cell disease was investigated. PATIENTS AND METHODS: The percent HbF and F cells were quantitated, and the HbF per F cell was then calculated. One hundred thirty-eight blood samples from 44 infants with homozygous sickle cell anemia (HbSS) and 56 samples from 24 infants with sickle cell hemoglobin (HbSC) were studied. RESULTS: Infants with HbSS had a logarithmic decline in HbF parameters; at 24 months, the average HbF was 14.6%+/-7.3% and the % F cells was 64.7%+/-16.9%. The amount of HbF in each F cell (HbF per F cell) was <15 pg/cell, a suggested threshold for intracellular sickle polymerization, by age 12 months. Infants with HbSC had a more rapid decline: at 12 months the average % HbF was 12.2%+/-9.3%, the % F cells was 60.5%+/-18.7%, and the HbF per F cell was <10 pg/cell. CONCLUSIONS: By age 2 years, HbF parameters including the % HbF, % F cells, and the HbF per F cell decrease to levels insufficient to inhibit sickling. Pharmacologic intervention designed to enhance HbF production and prevent chronic organ damage should be considered during infancy.

Aging↗

PubMedDate not supplied

Hydroxyurea therapy for pediatric patients with hemoglobin SC disease.

PURPOSE: Hydroxyurea (HU) has laboratory and clinical efficacy in hemoglobin SS (HbSS) disease, but its benefits in hemoglobin SC (HbSC) disease are unknown. A recent adult HbSC disease pilot trial with HU therapy documented a modest laboratory benefit. Our goal was to evaluate the laboratory and clinical responses of selected pediatric patients with severe HbSC disease to HU therapy. PATIENTS AND METHODS: As part of a retrospective case series, patients were selected from the Duke Pediatric Sickle Cell Program based on the frequency and severity of their vasoocclusive events or an episode of acute chest syndrome. Oral HU therapy was started as a single daily dose and increased to the maximally tolerated dose based on myelosuppression. Laboratory evaluation was performed at baseline and monthly thereafter. Once the maximum tolerated dose was reached, laboratory data were monitored bimonthly. RESULTS: We treated six severely affected pediatric HbSC patients with HU for a median of 27 months. Mean corpuscular volume increased significantly (+26 fL) without change in hemoglobin concentration (-0.1 g/dL); neutrophils decreased significantly. Percentage of fetal hemoglobin (+8.5%) and percentage of F cells (+35.7%) increased significantly. Two experienced only mild and reversible toxicity. CONCLUSION: The laboratory responses in our pediatric patients with HbSC disease were striking, with increases in percentage of fetal hemoglobin and percentage of F-cells approaching responses observed in adult and pediatric patients with HbSS disease. All patients improved clinically. Our findings demonstrate that HU therapy benefits pediatric patients with severe HbSC disease, although larger clinical trials of HU therapy in HbSC disease are warranted.

Acute Disease↗

PubMedDate not supplied

Recombinant human acid alpha-glucosidase enzyme therapy for infantile glycogen storage disease type II: results of a phase I/II clinical trial.

PURPOSE: Infantile glycogen storage disease type II (GSD-II) is a fatal genetic muscle disorder caused by deficiency of acid alpha-glucosidase (GAA). The purpose of this study was to investigate the safety and efficacy of recombinant human GAA (rhGAA) enzyme therapy for this fatal disorder. METHODS: The study was designed as a phase I/II, open-label, single-dose study of rhGAA infused intravenously twice weekly in three infants with infantile GSD-II. rhGAA used in this study was purified from genetically engineered Chinese hamster ovary (CHO) cells overproducing GAA. Adverse effects and efficacy of rhGAA upon cardiac, pulmonary, neurologic, and motor functions were evaluated during 1 year of the trial period. The primary end point assessed was heart failure-free survival at 1 year of age. This was based on historical control data that virtually all patients died of cardiac failure by 1 year of age. RESULTS: The results of more than 250 infusions showed that rhGAA was generally well tolerated. Steady decreases in heart size and maintenance of normal cardiac function for more than 1 year were observed in all three infants. These infants have well passed the critical age of 1 year (currently 16, 18, and 22 months old) and continue to have normal cardiac function. Improvements of skeletal muscle functions were also noted; one patient showed marked improvement and currently has normal muscle tone and strength as well as normal neurologic and Denver developmental evaluations. Muscle biopsies confirmed that dramatic reductions in glycogen accumulation had occurred after rhGAA treatment in this patient. CONCLUSIONS: This phase I/II first study of recombinant human GAA derived from CHO cells showed that rhGAA is capable of improving cardiac and skeletal muscle functions in infantile GSD-II patients. Further study will be needed to assess the overall potential of this therapy.

Age Factors↗