Dana Walker

Pretreatment antimüllerian hormone levels determine rate of posttherapy ovarian reserve recovery: acute changes in ovarian reserve during and after chemotherapy

OBJECTIVEnTo identify factors associated with ovarian reserve impairment during and immediately after chemotherapy.nnnDESIGNnProspective cohort study.nnnSETTINGnFour university hospitals.nnnPATIENT(S)nForty-six adolescent and young adult women with a new diagnosis of cancer requiring chemotherapy.nnnINTERVENTION(S)nNone.nnnMAIN OUTCOME MEASURE(S)nMeasurements of ovarian reserve via levels of serum follicle-stimulating hormone, luteinizing hormone, estradiol, inhibin B, and antimüllerian hormone (AMH) as well as antral follicle counts and mean ovarian volume at 3-month intervals.nnnRESULT(S)nChanges in ovarian reserve were quantified for both the acute impact of treatment using linear regression and the longitudinal recovery after therapy using mixed-effects models adjusted for baseline ovarian reserve, use of alkylating agent, and hormone use. The women had at least one pretreatment and two posttreatment study visits (mean follow-up interval: 12 months). All measures of ovarian reserve demonstrated statistically significant changes during chemotherapy. Alkylating agent exposure and baseline ovarian reserve were acutely associated with the magnitude of impairment, and pretreatment AMH levels were associated with the rate of recovery of AMH after treatment. In adjusted models, participants with a pretreatment AMH level > 2 ng/mL recovered at a rate of 11.9% per month after chemotherapy, whereas participants with pretreatment AMH levels ≤ 2 ng/mL recovered at a rate of 2.6% per month after therapy.nnnCONCLUSION(S)nBaseline ovarian reserve and alkylating agent exposure effect the magnitude of acute changes in ovarian reserve from chemotherapy. The rate of recovery of AMH is impacted by pretreatment levels. This should be considered during pretreatment fertility preservation counseling.

Establishment of an 11-year cohort of 8733 pediatric patients hospitalized at United States free-standing children's hospitals with de novo acute lymphoblastic leukemia from health care administrative data.

Background:Acute lymphoblastic leukemia (ALL) accounts for almost one quarter of pediatric cancer in the United States. Despite cooperative group therapeutic trials, there remains a paucity of large cohort data on which to conduct epidemiology and comparative effectiveness research studies. Research Design:We designed a 3-step process utilizing International Classification of Diseases-9 Clinical Modification (ICD-9) discharge diagnoses codes and chemotherapy exposure data contained in the Pediatric Health Information System administrative database to establish a cohort of children with de novo ALL. This process was validated by chart review at 1 of the pediatric centers. Results:An ALL cohort of 8733 patients was identified with a sensitivity of 88% [95% confidence interval (CI), 83%–92%] and a positive predictive value of 93% (95% CI, 89%–96%). The 30-day all cause inpatient case fatality rate using this 3-step process was 0.80% (95% CI, 0.63%–1.01%), which was significantly different than the case fatality rate of 1.40% (95% CI, 1.23%–1.60%) when ICD-9 codes alone were used. Conclusions:This is the first report of assembly and validation of a cohort of de novo ALL patients from a database representative of free-standing children’s hospitals across the United States. Our data demonstrate that the use of ICD-9 codes alone to establish cohorts will lead to substantial patient misclassification and result in biased outcome estimates. Systematic methods beyond the use of just ICD-9 codes must be used before analysis to establish accurate cohorts of patients with malignancy. A similar approach should be followed when establishing future cohorts from administrative data.

Dexrazoxane exposure and risk of secondary acute myeloid leukemia in pediatric oncology patients

Dexrazoxane may reduce anthracycline‐associated cardiotoxicity in pediatric cancer patients. However, concerns of secondary acute myeloid leukemia (AML) have led to restrictions on pediatric dexrazoxane use in Europe. Published data about dexrazoxane‐associated secondary AML are limited and conflicting. We sought to estimate the secondary AML risk in children receiving dexrazoxane after anthracycline exposure.

Outcome of pediatric acute myeloid leukemia patients receiving intensive care in the United States.

Objective: Children with acute myeloid leukemia are at risk for sepsis and organ failure. Outcomes associated with intensive care support have not been studied in a large pediatric acute myeloid leukemia population. Our objective was to determine hospital mortality of pediatric acute myeloid leukemia patients requiring intensive care. Design: Retrospective cohort study of children hospitalized between 1999 and 2010. Use of intensive care was defined by utilization of specific procedures and resources. The primary endpoint was hospital mortality. Setting: Forty-three children’s hospitals contributing data to the Pediatric Health Information System database. Patients: Patients who are newly diagnosed with acute myeloid leukemia and who are 28 days through 18 years old (n = 1,673) hospitalized any time from initial diagnosis through 9 months following diagnosis or until stem cell transplant. A reference cohort of all nononcology pediatric admissions using the same intensive care resources in the same time period (n = 242,192 admissions) was also studied. Interventions: None. Measurements and Main Results: One-third of pediatric patients with acute myeloid leukemia (553 of 1,673) required intensive care during a hospitalization within 9 months of diagnosis. Among intensive care admissions, mortality was higher in the acute myeloid leukemia cohort compared with the nononcology cohort (18.6% vs 6.5%; odds ratio, 3.23; 95% CI, 2.64–3.94). However, when sepsis was present, mortality was not significantly different between cohorts (21.9% vs 19.5%; odds ratio, 1.17; 95% CI, 0.89–1.53). Mortality was consistently higher for each type of organ failure in the acute myeloid leukemia cohort versus the nononcology cohort; however, mortality did not exceed 40% unless there were four or more organ failures in the admission. Mortality for admissions requiring intensive care decreased over time for both cohorts (23.7% in 1999–2003 vs 16.4% in 2004–2010 in the acute myeloid leukemia cohort, p = 0.0367; and 7.5% in 1999–2003 vs 6.5% in 2004–2010 in the nononcology cohort, p < 0.0001). Conclusions: Pediatric patients with acute myeloid leukemia frequently required intensive care resources, with mortality rates substantially lower than previously reported. Mortality also decreased over the time studied. Pediatric acute myeloid leukemia patients with sepsis who required intensive care had a mortality comparable to children without oncologic diagnoses; however, overall mortality and mortality for each category of organ failure studied was higher for the acute myeloid leukemia cohort compared with the nononcology cohort.

Leveraging Administrative Data to Monitor Rituximab Use in 2875 Patients at 42 Freestanding Children's Hospitals across the United States

OBJECTIVEnTo describe the pharmacoepidemiology of rituximab use in children and to estimate the frequency of infectious events within a 1-year period after rituximab exposure.nnnSTUDY DESIGNnThis is a retrospective cohort study of patients who received rituximab at 1 of 42 childrens hospitals contributing data to the Pediatric Health Information System between January 1999 and June 2011. International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) discharge diagnosis codes were analyzed to categorize underlying diseases (hematologic malignancies, primary immunodeficiencies, autoimmune diseases, and transplant recipients) and to estimate inpatient infectious complication rates within each category.nnnRESULTSnA total of 2875 patients with 4639 rituximab admissions were identified. The median age at index admission was 11 years (IQR, 5-15 years). The rate of rituximab admissions increased from 3 to 185 per 100,000 admissions per year over the study interval. During the 1-year follow-up period, 463 patients (16%) died. Infectious events were assessed in 2246 of the rituximab-exposed patients; 6.1% were diagnosed with sepsis and 2.0% with septic shock. The frequency of sepsis ranged from 2.4% in patients with autoimmune diseases to 12.2% in those with primary immunodeficiencies. Three patients were assigned an ICD-9-CM discharge diagnosis code for Pneumocystis joroveci pneumonia, 1 patient was assigned an ICD-9-CM discharge diagnosis code for hepatitis B, and 1 patient was assigned an ICD-9-CM discharge diagnosis code for progressive multifocal leukoencephalopathy.nnnCONCLUSIONnThe use of rituximab has increased significantly in children with a variety of underlying diseases. Based on ICD-9-CM code data, the rates of sepsis and other life-threatening infections after rituximab exposure vary depending on the underlying condition. Based on surveillance of infection using ICD-9-CM diagnosis codes, the rates of opportunistic infections appear to be low.

Dexrazoxane Use in Pediatric Patients With Acute Lymphoblastic or Myeloid Leukemia From 1999 and 2009: Analysis of a National Cohort of Patients in the Pediatric Health Information Systems Database

Acute lymphoblastic (ALL) and myeloid leukemia (AML) account for approximately 26% of pediatric cancers. Anthracyclines are widely used to treat these leukemias, but dosing is limited by cardiotoxicity. Data support the efficacy of dexrazoxane as a cardioprotectant in children; however, dexrazoxane use in children is not universally accepted due to concerns about toxicity, impact on the antitumor effect of anthracyclines, and risk of secondary malignant neoplasms (SMN).

Induction mortality and resource utilization in children treated for acute myeloid leukemia at free-standing pediatric hospitals in the United States

Clinical trials in pediatric acute myeloid leukemia (AML) determine induction regimen standards. However, these studies lack the data necessary to evaluate mortality trends over time and differences in resource utilization between induction regimens. Moreover, these trials likely underreport the clinical toxicities experienced by patients.

Variation in hospital antibiotic prescribing practices for children with acute lymphoblastic leukemia

Abstract Antibiotic variation among pediatric oncology patients has not been well-described. Identification of significant variability in antibiotic use within this population would warrant evaluation of its clinical impact. We conducted a retrospective cohort study of newly diagnosed patients with pediatric acute lymophoblastic leukemia (ALL) hospitalized from 1999 to 2009 in 39 freestanding US childrens hospitals within the Pediatric Health Information System. Medication use data were obtained for the first 30 days from each patients index ALL admission date. Antibiotic exposure rates were reported as antibiotic days/1000 hospital days. Unadjusted composite broad-spectrum antibiotic exposure rates varied from 577 to 1628 antibiotic days/1000 hospital days. This wide range of antibiotic exposure was unaffected by adjustment for age, gender, race and days of severe illness (adjusted range: 532–1635 days of antibiotic therapy/1000 hospital days). Antibiotic use for children with newly diagnosed ALL varies widely across childrens hospitals and is not explained by demographics or illness severity.

Induction mortality, ATRA administration, and resource utilization in a nationally representative cohort of children with acute promyelocytic leukemia in the United States from 1999 to 2009

Limited data exist on induction mortality of pediatric patients with acute promyelocytic leukemia in the United States, usage of all‐trans retinoic acid (ATRA) during acute promyelocytic leukemia induction, and the resources needed to deliver induction therapy.

Patient and hospital factors associated with induction mortality in acute lymphoblastic leukemia

Deaths during induction chemotherapy for pediatric acute lymphoblastic leukemia (ALL) account for one‐tenth of ALL‐associated mortality and half of ALL treatment‐related mortality. We sought to ascertain patient‐ and hospital‐level factors associated with induction mortality.