Skin and nail changes in children with sickle cell anemia receiving hydroxyurea therapy.

Skin and nail changes from long-term hydroxyurea therapy are reported in adults. Skin and nail changes, including nail hyperpigmentation, longitudinal bands, and hyperpigmentation of the palms and other skin surfaces, developed in 7 children with sickle cell anemia after 6 to 16 weeks of hydroxyurea therapy. Cutaneous and nail changes may occur in children receiving hydroxyurea.

Safety of hydroxyurea in children with sickle cell anemia: results of the HUG-KIDS study, a phase I/II trial. Pediatric Hydroxyurea Group.

Previous studies have determined the short-term toxicity profile, laboratory changes, and clinical efficacy associated with hydroxyurea (HU) therapy in adults with sickle cell anemia. The safety and efficacy of this agent in pediatric patients with sickle cell anemia has not been determined. Children with sickle cell anemia, age 5 to 15 years, were eligible for this multicenter Phase I/II trial. HU was started at 15 mg/kg/d and escalated to 30 mg/kg/d unless the patient experienced laboratory toxicity. Patients were monitored by 2-week visits to assess compliance, toxicity, clinical adverse events, growth parameters, and laboratory efficacy associated with HU treatment. Eighty-four children were enrolled between December 1994 and March 1996. Sixty-eight children reached maximum tolerated dose (MTD) and 52 were treated at MTD for 1 year. Significant hematologic changes included increases in hemoglobin concentration, mean corpuscular volume, mean corpuscular hemoglobin, and fetal hemoglobin parameters, and decreases in white blood cell, neutrophil, platelet, and reticulocyte counts. Laboratory toxicities typically were mild, transient, and were reversible upon temporary discontinuation of HU. No life-threatening clinical adverse events occurred and no child experienced growth failure. This Phase I/II trial shows that HU therapy is safe for children with sickle cell anemia when treatment was directed by a pediatric hematologist. HU in children induces similar laboratory changes as in adults. Phase III trials to determine if HU can prevent chronic organ damage in children with sickle cell anemia are warranted.

Hemoglobin S/O(Arab): thirteen new cases and review of the literature.

Hemoglobin S/O(Arab) (Hb S/O(Arab)) is a rare compound heterozygous hemoglobinopathy characterized by the presence of two variant beta-globin chains: beta6Glu --> Val (Hb S) and beta121Glu --> Lys (Hb O(Arab)). The diagnosis of Hb S/O(Arab) requires electrophoresis on both cellulose acetate and citrate agar, since Hb O(Arab) co-migrates with Hb C at alkaline pH and close to Hb S at acidic pH. To date only case reports and small series of patients with Hb S/O(Arab) have been described. To better characterize the clinical and laboratory aspects of this unusual disorder, we reviewed the Duke University Medical Center experience. We identified 13 African-American children and adults with Hb S/O(Arab) ranging in age from 2.7 to 62.5 years. All patients had hemolytic anemia with a median Hb of 8.7 gm/dL (range 6.1-9.9 gm/dL), and a median reticulocyte count of 5.8% (range 1.2-10.3%). The peripheral blood smear typically showed sickled erythrocytes, target cells, polychromasia, and nucleated red blood cells. All 13 patients have had significant clinical sickling events including acute chest syndrome (11), recurrent vasoocclusive painful events (10), dactylitis (7), gallstones (5), nephropathy (4), aplastic crises (2), avascular necrosis (2), leg ulcers (2), cerebrovascular accident (CVA) (1), osteomyelitis (1), and retinopathy (1). Four patients have died, including two from pneumococcal sepsis/meningitis at ages 5 and 10 years, one of acute chest syndrome at age 14 years, and one of multiorgan failure at age 35 years. We conclude that Hb S/O(Arab) disease is a severe sickling hemoglobinopathy with laboratory and clinical manifestations similar to those of homozygous sickle cell anemia.

Quantitative analysis of erythrocytes containing fetal hemoglobin (F cells) in children with sickle cell disease.

Variation in the level of fetal hemoglobin (HbF) accounts for much of the clinical heterogeneity observed in patients with sickle cell disease (SCD). The HbF level has emerged as an important prognostic factor in both sickle cell pain and mortality, and a % HbF of 10-20% has been suggested as a threshold level for diminished clinical severity. The number of erythrocytes that contain HbF (termed F cells) may also be critically important, as F cells resist intravascular sickling and have preferential in vivo survival. Since F cells can be enumerated with high accuracy using flow cytometry methods, we prospectively studied a cohort of 242 children with SCD. Children with HbS and hereditary persistence of fetal hemoglobin (S/HPFH) had essentially 100% F cells. In contrast, children with homozygous sickle cell anemia (HbSS), HbS/beta0 thalassemia, or HbS/beta+ thalassemia had significantly lower mean % F cell values (55.9, 61.6, and 51.3%, respectively; P < 0.001), and children with HbSC had even fewer F cells (27.0%; P < 0.001). There was a highly significant correlation between the % F cells and the log (% HbF), which was observed for the total population of children (r = 0.95, P < 0.001), as well as for each of the individual subgroups of children with HbSS (r = 0.94, P < 0.001), HbSC (r = 0.89, P < 0.001), or HbS/beta0 thalassemia and HbS/beta+ thalassemia (r = 0.95, P <0.001). This logarithmic correlation between % F cells and % HbF has not been previously described and has important implications for the pharmacologic manipulation of HbF in patients with SCD.