James G. Gurney

Neurocognitive Outcomes Decades After Treatment for Childhood Acute Lymphoblastic Leukemia: A Report From the St. Jude Lifetime Cohort Study

PURPOSEnTo determine rates, patterns, and predictors of neurocognitive impairment in adults decades after treatment for childhood acute lymphoblastic leukemia (ALL).nnnPATIENTS AND METHODSnSurvivors of childhood ALL treated at St Jude Childrens Research Hospital who were still alive at 10 or more years after diagnosis and were age ≥ 18 years were recruited for neurocognitive testing. In all, 1,014 survivors were eligible, 738 (72.8%) agreed to participate, and 567 (76.8%) of these were evaluated. Mean age was 33 years; mean time since diagnosis was 26 years. Medical record abstraction was performed for data on doses of cranial radiation therapy (CRT) and cumulative chemotherapy. Multivariable modeling was conducted and glmulti package was used to select the best model with minimum Akaike information criterion.nnnRESULTSnImpairment rates across neurocognitive domains ranged from 28.6% to 58.9%, and those treated with chemotherapy only demonstrated increased impairment in all domains (all P values < .006). In survivors who received no CRT, dexamethasone was associated with impaired attention (relative risk [RR], 2.12; 95% CI, 1.11 to 4.03) and executive function (RR, 2.42; 95% CI, 1.20 to 4.91). The impact of CRT was dependent on young age at diagnosis for intelligence, academic, and memory functions. Risk for executive function problems increased with survival time in a CRT dose-dependent fashion. In all survivors, self-reported behavior problems increased by 5% (RR, 1.05; 95% CI, 1.01 to 1.09) with each year from diagnosis. Impairment was associated with reduced educational attainment and unemployment.nnnCONCLUSIONnThis study demonstrates persistent and significant neurocognitive impairment in adult survivors of childhood ALL and warrants ongoing monitoring of brain health to facilitate successful adult development and to detect early onset of decline as survivors mature.

Bone mineral density among long-term survivors of childhood acute lymphoblastic leukemia: Results from the St. Jude Lifetime Cohort Study

The prevalence of low bone mineral density (BMD) in adult survivors of childhood acute lymphoblastic leukemia (ALL), and the degree of recovery or decline, are not well elucidated.

Assessment of potential bias from non-participation in a dynamic clinical cohort of long-term childhood cancer survivors: results from the St. Jude Lifetime Cohort Study.

To evaluate long‐term health outcomes among childhood cancer survivors, St. Jude Childrens Research Hospital (SJCRH) has established the St. Jude Lifetime Cohort Study (SJLIFE), comprised of adult survivors who undergo risk‐directed clinical assessments. As in any human research study, SJLIFE participants are volunteers who may not represent the source population from which they were recruited. A lack of proportional representation could result in biased estimates of exposure‐outcome associations. We compared available demographic, disease, and neighborhood level characteristics between participants and the source population to assess the potential for selection bias.

Adverse effects of treatment in childhood acute lymphoblastic leukemia: general overview and implications for long-term cardiac health

Survival of childhood acute lymphoblastic leukemia (ALL) is one of the greatest medical success stories of the last four decades. Unfortunately, childhood ALL survivors experience medical late effects that increase their risk of morbidity and premature death, often due to heart and vascular disease. Research has helped elucidate the mechanisms and trajectory of direct damage to the heart from treatment exposure, particularly to anthracyclines, and has also contributed knowledge on the influences of related chronic conditions, such as obesity and insulin resistance on heart health in these survivors. This article summarizes the key issues associated with early morbidity and mortality from cardiac-related disease in childhood ALL survivors and suggests directions for interventions to improve long-term outcomes.

Chemotherapy-related neuropathic symptoms and functional impairment in adult survivors of extracranial solid tumors of childhood: results from the St. Jude Lifetime Cohort Study.

OBJECTIVESnTo ascertain prevalence of peripheral sensory and motor neuropathy, and to evaluate impairments in relation to function.nnnDESIGNnSt. Jude Lifetime Cohort Study, a clinical follow-up study designed to evaluate adverse late effects in adult survivors of childhood cancer.nnnSETTINGnA childrens research hospital.nnnPARTICIPANTSnEligibility required treatment for an extracranial solid malignancy between 1962 and 2002, age ≥ 18 years, ≥ 10 years postdiagnosis, and no history of cranial radiation. Survivors (N=531) were included in the evaluation with a median age of 32 years and a median time from diagnosis of 25 years.nnnINTERVENTIONSnNot applicable.nnnMAIN OUTCOME MEASURESnPrimary exposure measures were cumulative doses of vinca-alkaloid and platinum-based chemotherapies. Survivors with scores ≥ 1 on the sensory subscale of the Modified Total Neuropathy Score were classified with prevalent sensory impairment. Those with sex-specific z scores of ≤-1.3 for dorsiflexion strength were classified with prevalent motor impairment. Participants completed the 6-minute walk test (endurance), the Timed Up & Go test (mobility), and the Sensory Organization Test (balance).nnnRESULTSnThe prevalence of sensory and motor impairment was 20% and 17.5%, respectively. Vinca-alkaloid exposure was associated with an increased risk of motor impairment (adjusted odds ratio [OR]=1.66; 95% confidence interval [CI], 1.04-2.64) without evidence for a dose response. Platinum exposure was associated with increased risk of sensory impairment (adjusted OR=1.62; 95% CI, .97-2.72) without evidence of a dose response. Sensory impairment was associated with poor endurance (OR=1.99; 95% CI, .99-4.0) and mobility (OR=1.65; 95% CI, .96-2.83).nnnCONCLUSIONSnVincristine and cisplatin exposure may increase risk for long-term motor and sensory impairment, respectively. Survivors with sensory impairment are at increased risk for functional performance limitations.

The accuracy of human papillomavirus vaccination status based on adult proxy recall or household immunization records for adolescent females in the United States: results from the National Immunization Survey-Teen

PURPOSEnWe assessed the accuracy of human papillomavirus (HPV) vaccination status based on adult proxy recall and household immunization records for adolescent females in the United States.nnnMETHODSnWe used data from the 2010 National Immunization Survey-Teen for females aged 13 to 17 years. The accuracy of HPV vaccination status (≥1 dose) based on adult proxy recall (unweighted n = 6868) and household immunization records (unweighted n = 2216) was assessed by estimating the sensitivity, specificity, and corresponding 95% confidence limits (CL) of these measures with provider-reported HPV vaccination status as the reference standard. Our analyses accounted for the complex survey design and population weights.nnnRESULTSnThe sensitivity and specificity of adult proxy recall were 83.9% (95% CL: 81.2%, 86.6%) and 90.4% (95% CL: 88.9%, 92.0%), respectively. Conversely, the sensitivity and specificity of household immunization records were 74.2% (95% CL: 69.1%, 79.2%) and 98.0% (95% CL: 96.8%, 99.1%), respectively. The accuracy of both measures varied by race/ethnicity, proxy respondent, and maternal education.nnnCONCLUSIONSnOur results suggest that adult proxy recall and household immunization records have reasonable accuracy for classifying HPV vaccination status for females aged 13 to 17 years in the United States, but these measures present a trade-off between sensitivity and specificity.

Junctional Ectopic Tachycardia After Infant Heart Surgery: Incidence and Outcomes

Junctional ectopic tachycardia (JET) is an arrhythmia observed almost exclusively after open heart surgery in children. Current literature on JET has not focused on patients at the highest risk of both developing and being negatively impacted by JET. The purpose of this study was to determine the overall incidence of JET in an infant patient cohort undergoing open cardiac surgery, to identify patient- and procedure-related factors associated with developing JET, and to assess the clinical impact of JET on patient outcomes. We performed a nested case-control study from the complete cohort of patients at our institution younger than 1xa0year of age who underwent open heart surgery between 2005 and 2010. JET patients were compared with an age matched control group undergoing open heart surgery without JET regarding potential risk factors and outcomes. The overall incidence of JET in infants after open cardiac surgery was 14.3xa0%. From multivariate analyses, complete repair of tetralogy of Fallot [adjusted odds ratio (AOR) 2.0, 95xa0% CI 1.12–3.57] and longer aortic cross clamp times (AOR 1.02, 95xa0% CI 1.01–1.03) increased the risk of developing JET. Patients with JET had longer length of intubation, intensive care unit stays, and total length of hospitalization, and were more likely to require extracorporeal membrane oxygenation support (13 vs. 4.3xa0%). JET is a common postoperative arrhythmia in infants after open heart operations. Both anatomic substrate and surgical procedure contribute to the overall risk of developing JET. Developing JET is associated with worse clinical outcomes.

Hydroxyurea use and hospitalization trends in a comprehensive pediatric sickle cell program.

Background A decline in hospitalizations and pain episodes among those with sickle cell disease (SCD) who take hydroxyurea (HU) has been shown when compared to pre-HU patterns but paradoxically, when compared to those who have never been treated, HU recipients often have more frequent hospitalizations. This analysis evaluates the impact of increasing usage of HU on trends in hospitalizations and blood transfusions within a large SCD treatment program. Methods Eligibility was restricted to patients with Hb SS or Hb Sβ0-thalassemia who were 2–18 years old between 2006–2010 and received care at St. Jude Childrens Research Hospital (Nu200a=u200a508). Hospitalizations and blood transfusions were calculated for each of the years under study for those exposed and never exposed to HU. Differences in number of hospitalizations before and after HU initiation were compared. Results The proportion of patients receiving HU increased by 4% per year on average. In the HU exposed group, a modest decline in mean per-patient hospitalizations and per-patient hospital days occurred, while those never exposed to HU trended toward a slight increase over time. Rates of blood transfusions declined among those on HU but not in patients never exposed to HU. Patients on HU had a median of one fewer hospital admission in the year after initiation of HU, compared to the year prior. Two deaths occurred in the patient population, both of whom were not exposed to HU. Conclusions Increasing usage of HU was concurrent with decreased hospitalization rates and blood transfusions. Our results support the utility of HU on decreasing hospitalizations and transfusions for patients with SCD outside of the clinical trial setting.

Treatment-induced hearing loss and adult social outcomes in survivors of childhood CNS and non-CNS solid tumors: Results from the St. Jude Lifetime Cohort Study.

Survivors of childhood cancer who are treated with platinum‐based chemotherapy and/or cranial radiation are at risk of treatment‐induced hearing loss. However, the effects of such hearing loss on adult social attainment have not been well elucidated.

Genetic and clinical factors associated with obesity among adult survivors of childhood cancer: A report from the St. Jude Lifetime Cohort.

The objective of this study was to identify treatment and genetic factors associated with obesity among childhood cancer survivors.