EFFECT OF HYDROXYUREA IN SICKLE CELL ANEMIA: A Clinical Trial in Children and Teenagers with Severe Sickle Cell Anemia and Sickle Cell beta-Thalassemia

218

Pain and acute chest syndrome (ACS) episodes are 2 of the most common causes of hospitalization in children with sickle cell anemia (SCA). However, very few potentially modifiable risk factors for either condition have been identified. In this prospective infant cohort study, we tested the hypothesis that asthma is associated with an increased incidence rate of pain and ACS episodes. An infant cohort was composed of 291 African American children with hemoglobin SS enrolled in the Cooperative Study for Sickle Cell Disease before age 6 months and followed beyond age 5 years. Asthma was defined by a physician diagnosis, an acute asthma event, or use of prescription asthma medications. The incidence rates of ACS and painful episodes were compared for children with and without asthma. A clinical diagnosis of asthma was made in 17% of the cohort. Asthma was associated with more frequent ACS episodes (0.39 vs 0.20 events per patient year, P < .001) and painful episodes (1.39 vs 0.47 events per patient year, P < .001). In conclusion, in children with SCA, asthma is associated with an increased incidence of sickle cell disease-related morbidity, including ACS and painful episodes. IntroductionPainful episodes and acute chest syndrome (ACS) are common complications of sickle cell anemia (SCA) and are the 2 leading causes of hospitalization among people with SCA. 1,2 ACS affects up to 50% of individuals with SCA and is the leading cause of premature death. [2][3][4] The pathogenesis of ACS is multifactorial and remains unclear. In a large prospective study, several etiologies were identified, but in approximately 50% of episodes, no cause was determined. 5 Known risk factors for the development of ACS include younger age, degree of anemia (higher steady-state hemoglobin level), lower hemoglobin F, and higher steady-state white blood cell count. 2,6 Asthma is a common chronic disease affecting approximately 15% to 20% of African American children. [7][8][9][10] Previous retrospective studies suggest a relationship between ACS and asthma among children with SCA. We previously reported a 4-fold higher risk of ACS among children with SCA and a prior doctor diagnosis of asthma within a cohort of children with SCA hospitalized for pain. 11 Knight-Madden et al 12 reported a 6-fold higher risk of recurrent ACS among children with SCA and a parental report of doctor-diagnosed asthma. Airway obstruction and airway lability have been previously described in patients with SCA, suggesting that asthma may contribute to the pulmonary complications of the disease. [13][14][15][16] These data suggest that in children with SCA, a diagnosis of asthma may be a risk factor for ACS. This study also seeks to determine whether asthma is also associated with painful episodes, a common complication in SCA that often precedes or occurs concurrently with ACS episodes.In a cohort of infants established and followed for 20 years by the Cooperative Study of Sickle Cell Disease (CSSCD), we tested the hypothesis that a concurrent diagnosis of asthma in p...

Section: Discussionmentioning

confidence: 99%

Asthma is associated with acute chest syndrome and pain in children with sickle cell anemia

Boyd

Macklin

Strunk

et al. 2006

218

“…50,61,90 Of note, several reports confirm that the effects of hydroxyurea in patients with hemoglobin S/b-thalassemia may be better than those even reported for homozygous hemoglobin S disease, because the synthesized g-chains not only inhibit the sickling process, but they also neutralize the noxious effects of the excess a-chains and cut down on ineffective erythropoiesis. [91][92][93][94][95] Co-inheritance of a-thalassemia was described as a predictor of good response in some studies, 44,77,96 but it was found to have no effect in others. 49,68,85 Homozygosity for the XmnI polymorphism (2158C.…”

Section: Predictors Of Responsementioning

confidence: 99%

Clinical experience with fetal hemoglobin induction therapy in patients with β-thalassemia

Musallam

Taher

Cappellini

et al. 2013

176

139

Recent molecular studies of fetal hemoglobin (HbF) regulation have reinvigorated the field and shown promise for the development of clinical HbF inducers to be used in patients with β-thalassemia and sickle cell disease. However, while numerous promising inducers of HbF have been studied in the past in β-thalassemia patient populations, with limited success in some cases, no universally effective agents have been found. Here we examine the clinical studies of such inducers in an attempt to systematically review the field. We examine trials of agents, including 5-azacytidine, hydroxyurea, and short-chain fatty acids. This review highlights the heterogeneity of clinical studies done on these agents, including both the patient populations examined and the study end points. By examining the published studies of these agents, we hope to provide a resource that will be valuable for the design of future studies of HbF inducers in β-thalassemia patient populations.

“…18 Clinically, hydroxyurea has been shown to decrease the rate of pain and acute chest syndrome (ACS) events in severely affected adults and children. [8][9][10][11]19,20 Organ damage starts very early in life, and most children with SCA lose splenic reticuloendothelial function by 2 years of age. 1 The efficacy of hydroxyurea for the prevention of chronic organ damage in SCA and the potential benefit of dose escalation have not been fully investigated.…”

Section: Introductionmentioning

confidence: 99%

Long-term hydroxyurea therapy for infants with sickle cell anemia: the HUSOFT extension study

Hankins

Ware

Rogers

et al. 2005

249

217