Julie A. Panepinto

Acute care utilization and rehospitalizations for sickle cell disease.

CONTEXT Published rates of health care utilization and rehospitalization by people with sickle cell disease have had limited generalizability and are not population based. OBJECTIVE To provide benchmark data for rates of acute care utilization and rehospitalizations for patients with sickle cell disease. DESIGN Retrospective cohort of sickle cell disease-related emergency department (ED) visits and hospitalizations from select states in the 2005 and 2006 Healthcare Cost and Utilization Project (HCUP) State Inpatient Databases and State Emergency Department Databases. SETTING Eight geographically dispersed states (Arizona, California, Florida, Massachusetts, Missouri, New York, South Carolina, and Tennessee) that provide encrypted identifiers and have sufficient numbers of patients with sickle cell disease; together these states have 33% of the US population with sickle cell disease. PATIENTS A total of 21,112 patients with sickle cell-related treat-and-release ED visits or inpatient hospitalizations. MAIN OUTCOME MEASURES Rates of acute care utilization and rehospitalizations. Population-based utilization rates were also calculated. RESULTS The 21,112 people with sickle cell disease had 109,344 encounters, a mean of 2.59 (95% confidence interval [CI], 2.53-2.65) encounters per patient per year, 1.52 (95% CI, 1.48-1.55) encounters for hospitalizations and 1.08 (95% CI, 1.04-1.11) for treat-and-release ED visits. Utilization was highest for 18- to 30-year-olds, 3.61 (95% CI, 3.47-3.75) encounters per patient per year, and those with public insurance, 3.22 (95% CI, 3.13-3.31) encounters per patient per year. Publicly insured 18- to 30-year-olds had 4.80 (95% CI, 4.58-5.02) encounters per patient per year. Approximately 29% of the population had no encounters while 16.9% had 3 or more encounters per year. The 30-day and 14-day rehospitalization rates were 33.4% (95% CI, 33.0%-33.8%) and 22.1% (95% CI, 21.8%-22.4%), respectively. The rehospitalization rate was highest for 18- to 30-year-olds, with 41.1% (95% CI, 40.5%-41.7%) rehospitalized within 30 days and 28.4% (95% CI, 27.8%-29.0%) within 14 days. Rehospitalizations were also highest for publicly insured patients. CONCLUSION Among patients with sickle cell disease, acute care encounters and rehospitalizations were frequent, particularly for 18- to 30-year-olds.

Controlled Trial of Transfusions for Silent Cerebral Infarcts in Sickle Cell Anemia

BACKGROUND Silent cerebral infarcts are the most common neurologic injury in children with sickle cell anemia and are associated with the recurrence of an infarct (stroke or silent cerebral infarct). We tested the hypothesis that the incidence of the recurrence of an infarct would be lower among children who underwent regular blood-transfusion therapy than among those who received standard care. METHODS In this randomized, single-blind clinical trial, we randomly assigned children with sickle cell anemia to receive regular blood transfusions (transfusion group) or standard care (observation group). Participants were between 5 and 15 years of age, with no history of stroke and with one or more silent cerebral infarcts on magnetic resonance imaging and a neurologic examination showing no abnormalities corresponding to these lesions. The primary end point was the recurrence of an infarct, defined as a stroke or a new or enlarged silent cerebral infarct. RESULTS A total of 196 children (mean age, 10 years) were randomly assigned to the observation or transfusion group and were followed for a median of 3 years. In the transfusion group, 6 of 99 children (6%) had an end-point event (1 had a stroke, and 5 had new or enlarged silent cerebral infarcts). In the observation group, 14 of 97 children (14%) had an end-point event (7 had strokes, and 7 had new or enlarged silent cerebral infarcts). The incidence of the primary end point in the transfusion and observation groups was 2.0 and 4.8 events, respectively, per 100 years at risk, corresponding to an incidence rate ratio of 0.41 (95% confidence interval, 0.12 to 0.99; P=0.04). CONCLUSIONS Regular blood-transfusion therapy significantly reduced the incidence of the recurrence of cerebral infarct in children with sickle cell anemia. (Funded by the National Institute of Neurological Disorders and Stroke and others; Silent Cerebral Infarct Multi-Center Clinical Trial ClinicalTrials.gov number, NCT00072761, and Current Controlled Trials number, ISRCTN52713285.).

The number of people with sickle-cell disease in the United States: national and state estimates.

Sickle-cell disease is not a reportable condition, making it difficult to ascertain the number of affected individuals. We estimated the number of people with sickle-cell disease for the United States and each individual state, adjusting for increased mortality. US Census population data for each of the 50 states plus the District of Columbia were obtained. The published prevalence of sickle-cell disease for blacks and Hispanics of either Mexican or non-Mexican ancestry was applied. Analysis revealed 89,079 (95% confidence interval: 88,494―89,664) people with sickle-cell disease in the United States, 80,151 black and 8928 Hispanic. The state with the highest sickle-cell population was New York with 8308, followed by Florida with 7539, and Texas with 6765 people with sickle-cell disease. This study provides important information for researchers and policymakers attempting to better plan for the care of the sickle-cell population.

Silent cerebral infarcts occur despite regular blood transfusion therapy after first strokes in children with sickle cell disease

Children with sickle cell disease (SCD) and strokes receive blood transfusion therapy for secondary stroke prevention; despite this, approximately 20% experience second overt strokes. Given this rate of second overt strokes and the clinical significance of silent cerebral infarcts, we tested the hypothesis that silent cerebral infarcts occur among children with SCD being transfused for secondary stroke prevention. A prospective cohort enrolled children with SCD and overt strokes at 7 academic centers. Magnetic resonance imaging and magnetic resonance angiography of the brain were scheduled approximately every 1 to 2 years; studies were reviewed by a panel of neuroradiologists. Eligibility criteria included regularly scheduled blood transfusion therapy. Forty children were included; mean pretransfusion hemoglobin S concentration was 29%. Progressive cerebral infarcts occurred in 45% (18 of 40 children) while receiving chronic blood transfusion therapy; 7 had second overt strokes and 11 had new silent cerebral infarcts. Worsening cerebral vasculopathy was associated with new cerebral infarction (overt or silent; relative risk = 12.7; 95% confidence interval, 2.65-60.5, P = .001). Children with SCD and overt strokes receiving regular blood transfusion therapy experience silent cerebral infarcts at a higher rate than previously recognized. Additional therapies are needed for secondary stroke prevention in children with SCD.

Health‐related quality of life in children with sickle cell disease: child and parent perception

Health‐related quality of life (HRQL) is an outcome that may be used to measure the impact of sickle cell disease on the child and their family but has not been routinely assessed in this disease. The objective of this study was to describe the HRQL of children with sickle cell disease as reported by the parent and the child, to compare the relationship between the two, and to determine the association of parent, child and disease characteristics on HRQL. Ninety‐five parents completed the Child Health Questionnaire (CHQ)‐Parent Form28 and 53 children completed the CHQ‐Child Form87. Compared with the child report, parents reported worse HRQL in the overall perception of health, physical functioning, behaviour and self esteem domains of HRQL (P < 0·005). Parent and child reports of HRQL correlated strongly in assessment of the impact of bodily pain (r = 0·58) on HRQL and moderately in physical functioning (r = 0·44), behaviour (r = 0·45), general health (r = 0·44), self esteem (r = 0·40) and changes in health (r = 0·33) domains. Disease status, neurobehavioral co‐morbidities, and parent education were associated with the HRQL of the child. Both the parent and child perspectives are needed to fully understand the impact of sickle cell disease on the HRQL of the child and effect of this disease on the family.

Matched-related donor transplantation for sickle cell disease: report from the Center for International Blood and Transplant Research

We report outcomes after myeloablative haematopoietic cell transplantation (HCT) from human leucocyte antigen (HLA)‐matched sibling donors in 67 patients with sickle cell disease transplanted between 1989 and 2002. The most common indications for transplantation were stroke and recurrent vaso‐occlusive crisis in 38% and 37% of patients respectively. The median age at transplantation was 10 years and 67% of patients had received >10 red blood cell transfusions before HCT. Twenty‐seven percent of patients had a poor performance score at transplantation. Ninety‐four percent received busulfan and cyclophosphamide‐containing conditioning regimens and bone marrow was the predominant source of donor cells. Most patients achieved haematopoietic recovery and no deaths occurred during the early post‐transplant period. Rates of acute and chronic graft‐versus‐host disease were 10% and 22% respectively. Sixty‐four of 67 patients are alive with 5‐year probabilities of disease‐free and overall survival of 85% and 97% respectively. Nine patients had graft failure with recovery of sickle erythropoiesis, eight of who had recurrent sickle‐related events. This report confirms and extends earlier reports that HCT from HLA‐matched related donors offers a very high survival rate, with few transplant‐related complications and the elimination of sickle‐related complications in the majority of patients who undergo this therapy.

Unrelated Donor Cord Blood Transplantation for Children with Severe Sickle Cell Disease: Results of One Cohort from the Phase II Study from the Blood and Marrow Transplant Clinical Trials Network (BMT CTN)

The Sickle Cell Unrelated Donor Transplant Trial (SCURT trial) of the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) is a phase II study of the toxicity and efficacy of unrelated donor hematopoietic cell transplantation in children with severe sickle cell disease (SCD) using a reduced-intensity conditioning regimen. Here we report the results for the cord blood cohort of this trial. Eight children with severe SCD underwent unrelated donor cord blood transplantation (CBT) following alemtuzumab, fludarabine, and melphalan. Cyclosporine or tacrolimus and mycophenolate mofetil were administered for graft-versus-host disease (GVHD) prophylaxis. Donor/recipient HLA match status was 6 of 6 (n = 1) or 5 of 6 (n = 7), based on low/intermediate-resolution molecular typing at HLA -A, -B, and high-resolution typing at -DRB1. Median recipient age was 13.7 years (range: 7.4-16.2 years), and median weight was 35.0 kg (range: 25.2-90.2 kg). The median pre-cryopreservation total nucleated cell dose was 6.4 × 10(7) /kg (range: 3.1-7.6), and the median postthaw infused CD34 cell dose was 1.5 × 10(5) /kg (range: 0.2-2.3). All patients achieved neutrophil recovery (absolute neutrophil count >500/mm(3)) by day 33 (median: 22 days). Three patients who engrafted had 100% donor cells by day 100, which was sustained, and 5 patients had autologous hematopoietic recovery. Six of 8 patients had a platelet recovery to >50,000/mm(3) by day 100. Two patients developed grade II acute GVHD. Of these, 1 developed extensive chronic GVHD and died of respiratory failure 14 months posttransplantation. With a median follow-up of 1.8 years (range: 1-2.6), 7 patients are alive with a 1-year survival of 100%, and 3 of 8 are alive without graft failure or disease recurrence. Based upon the high incidence of graft rejection after unrelated donor CBT, enrollment onto the cord blood arm of the SCURT trial was suspended. However, because this reduced-intensity regimen has demonstrated a favorable safety profile, this trial remains open to enrollment for unrelated marrow donor transplants. Novel approaches aimed at improving engraftment will be needed before unrelated CBT can be widely adopted for transplanting patients with severe SCD.

Associated risk factors for silent cerebral infarcts in sickle cell anemia: low baseline hemoglobin, sex, and relative high systolic blood pressure

The most common form of neurologic injury in sickle cell anemia (SCA) is silent cerebral infarction (SCI). In the Silent Cerebral Infarct Multi-Center Clinical Trial, we sought to identify risk factors associated with SCI. In this cross-sectional study, we evaluated the clinical history and baseline laboratory values and performed magnetic resonance imaging of the brain in participants with SCA (HbSS or HbSβ° thalassemia) between the ages of 5 and 15 years with no history of overt stroke or seizures. Neuroradiology and neurology committees adjudicated the presence of SCI. SCIs were diagnosed in 30.8% (251 of 814) participants who completed all evaluations and had valid data on all prespecified demographic and clinical covariates. The mean age of the participants was 9.1 years, with 413 males (50.7%). In a multivariable logistic regression analysis, lower baseline hemoglobin concentration (P < .001), higher baseline systolic blood pressure (P = .018), and male sex (P = .030) were statistically significantly associated with an increased risk of an SCI. Hemoglobin concentration and systolic blood pressure are risk factors for SCI in children with SCA and may be therapeutic targets for decreasing the risk of SCI. This study is registered at www.clinicaltrials.gov as #NCT00072761.

Attitudes regarding fertility preservation in female adolescent cancer patients.

Infertility is a devastating side effect of cancer treatment. Advances in fertility research have brought new preservation techniques to the forefront for women. The implication of this research in the field of pediatric oncology has not been reported. The objective of this study was to determine whether female adolescents with a diagnosis of cancer and their parents were interested in trying to preserve fertility. We conducted a cross-sectional survey of female patients, aged 10 to 21 years, and their parents. There were 39 parent/adolescent pair responses, 3 parent-only responses, and 8 adolescent-only responses. We found that adolescents and parents had thought about the future and were interested in research treatments to help preserve fertility, but not willing to postpone cancer therapy. Achieving a state of good health was most important to the adolescent group (P<0.001). There was no statistical difference between attitudes of parents and adolescents. In summary, parents and female adolescents are interested in options to help preserve fertility during cancer treatments, but they are not willing to postpone treatment for this purpose.

Health‐related quality of life in sickle cell disease: Past, present, and future

Health‐related quality of life (HRQL) is defined as the patients appraisal of how his/her well being and level of functioning, compared to the perceived ideal, are affected by individual health. The study of HRQL in children and adults with sickle cell disease (SCD) has begun to flourish. Given the devastating complications of the disease and other co‐morbid factors patients experience that influence HRQL, it is increasingly important to understand HRQL. The focus of this critical review was to examine past and current research in HRQL in SCD where a validated instrument was used. In addition, future directions for HRQL in SCD are explored. Pediatr Blood Cancer 2012;59:377–385.