Genomic architecture and treatment outcome in pediatric acute myeloid leukemia: a Children's Oncology Group report.

Childhood acute myeloid leukemia (AML) is frequently characterized by chromosomal instability. Approximately 50% of patients have disease relapse, and novel prognostic markers are needed to improve risk stratification. We performed genome-wide genotyping in 446 pediatric patients with de novo AML enrolled in Children's Oncology Group (COG) studies AAML0531, AAML03P1, and CCG2961. Affymetrix and Illumina Omni 2.5 platforms were used to evaluate copy-number alterations (CNAs) and determine their associations with treatment outcome. Data from Affymetrix and Illumina studies were jointly analyzed with ASCAT and GISTIC software. An average of 1.14 somatically acquired CNAs per patient were observed. Novel reoccurring altered genomic regions were identified, and the presence of CNAs was found to be associated with decreased 3-year overall survival (OS), event-free survival (EFS), and relapse risk from the end of induction 1 (hazard ratio [HR], 1.7; 95% confidence interval [CI], 1.2-2.4; HR, 1.4; 95% CI, 1.0-1.8; and HR, 1.4; 95% CI, 1.0-2.0, respectively). Analyses by risk group demonstrated decreased OS and EFS in the standard-risk group only (HR, 1.9; 95% CI, 1.1-3.3 and HR, 1.7; 95% CI, 1.1-2.6, respectively). Additional studies are required to test the prognostic significance of CNA presence in disease relapse in patients with AML. COG studies AAML0531, AAML03P1, and CCG2961 were registered at www.clinicaltrials.gov as #NCT01407757, #NCT00070174, and #NCT00003790, respectively.

Concordance of copy number alterations using a common analytic pipeline for genome-wide analysis of Illumina and Affymetrix genotyping data: a report from the Children's Oncology Group.

Copy number alterations (CNAs) are a hallmark of pediatric cancer genomes. An increasing number of research groups use multiple platforms and software packages to detect and analyze CNAs. However, different platforms have experimental and analysis-specific biases that may yield different results. We sought to estimate the concordance of CNAs in children with de novo acute myeloid leukemia between two experimental platforms: Affymetrix SNP 6.0 array and Illumina OmniQuad 2.5 BeadChip. Forty-five paired tumor-remission samples were genotyped on both platforms, and CNAs were estimated from total signal intensity and allelic contrast values using the allele-specific copy number analysis of tumors (ASCAT) algorithm. The two platforms were comparable in detection of CNAs, each missing only two segments from a total of 42 CNAs (4.6%). Overall, there was an interplatform agreement of 96% for allele-specific tumor profiles. However, poor quality samples with low signal/noise ratios showed a high rate of false-positive segments independent of the genotyping platform. These results demonstrate that a common analytic pipeline can be utilized for SNP array data from these two platforms. The customized programming template for the preprocessing, data integration, and analysis is publicly available at https://github.com/AplenCHOP/affyLumCNA.

Association of weekend admission with hospital length of stay, time to chemotherapy, and risk for respiratory failure in pediatric patients with newly diagnosed leukemia at freestanding US children's hospitals.

IMPORTANCE: In adult patients with leukemia, weekend admission is associated with increased inpatient mortality. It is unknown whether weekend diagnostic admissions in pediatric patients with leukemia demonstrate similar adverse outcomes. OBJECTIVE: To estimate adverse clinical outcomes associated with weekend admission in the first hospitalization of pediatric patients with newly diagnosed leukemia. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study from 1999 to 2011 featured index hospital admissions identified from the Pediatric Health Information System database. Participants were children with newly diagnosed acute lymphoid leukemia or acute myeloid leukemia. EXPOSURES: Weekend (Saturday and Sunday) or weekday index admission. MAIN OUTCOMES AND MEASURES: Inpatient mortality, length of inpatient stay, time to chemotherapy, and organ-system failure in index admission. RESULTS: A total of 10 720 patients with acute lymphoid leukemia and 1323 patients with acute myeloid leukemia were identified; 2009 patients (16.7%) were admitted on the weekend. While the total daily number of patients receiving intensive care unit-level care was constant regardless of the day of admission, these patients represented a larger percentage of total admissions on weekends. In adjusted analyses, patients admitted on the weekend did not have an increased rate of mortality during the first admission (odds ratio, 1.0; 95% CI, 0.8-1.6). Patients whose initial admission for leukemia occurred during a weekend had a significantly increased length of stay (1.4-day increase; 95% CI, 0.7-2.1), time to initiation of chemotherapy (0.36-day increase; 95% CI, 0.3-0.5), and risk for respiratory failure (odds ratio, 1.5; 95% CI, 1.2-1.7) after adjusting for demographics, severity of illness, and hospital-level factors. CONCLUSIONS AND RELEVANCE: While pediatric patients with newly diagnosed leukemia admitted on weekends do not have higher mortality rates, they have a prolonged length of stay, increased time to chemotherapy, and higher risk for respiratory failure. Patients who are severely ill at presentation represent a higher proportion of weekend index admissions. Optimizing weekend resources by increasing staffing and access to diagnostic and therapeutic resources may help to reduce hospital length of stay across all weekend admissions and may also ensure the availability of comprehensive care for those weekend admissions with higher acuity.