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Background: 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., Procedure: We performed a retrospective cohort analysis of 8,516 children ages 0 to <19 years with newly diagnosed ALL admitted to freestanding US children's hospitals from 1999 to 2009 using the Pediatric Health Information System database. Induction mortality risk was modeled accounting for demographics, intensive care unit-level interventions, and socioeconomic status (SES) using Cox regression. The association of ALL induction mortality with hospital-level factors including volume, hospital-wide mortality and payer mix was analyzed with multiple linear regression., Results: ALL induction mortality was 1.12%. Race and patient-level SES factors were not associated with induction mortality. Patients receiving both mechanical ventilation and vasoactive infusions experienced nearly 50% mortality (hazard ratio 122.30, 95% CI 66.56-224.80). Institutions in the highest induction mortality quartile contributed 27% of all patients but nearly half of all deaths (47 of 95). Hospital payer mix was associated with ALL induction mortality after adjustment for other hospital-level factors (P = 0.046)., Conclusions: The overall risk of induction death is low but substantially increased in patients with cardio-respiratory and other organ failures. Induction mortality varies up to three-fold across hospitals and is correlated with hospital payer mix. Further work is needed to improve induction outcomes in hospitals with higher mortality. These data suggest an induction mortality rate of less than 1% may be an attainable national benchmark., (© 2013 Wiley Periodicals, Inc.)

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.

There is little known about the impact of the timing of influenza vaccine administration on seroconversion in patients on chemotherapy. Recommendations for other vaccines state that the vaccines should be readministered several months after the completion of chemotherapy outside of the stem cell transplant setting. This is not often possible with the influenza vaccine because of its seasonal nature. To examine whether certain times during chemotherapy are more favorable for seroconversion, we examined vaccine responses in a cohort of children on chemotherapy. Pediatric patients on chemotherapy were recruited over the 2006 to 2008 influenza vaccine seasons. Sixty-eight acute lymphoblastic leukemia (ALL), 3 acute myeloid leukemia, and 18 sarcoma patients were evaluated. Clinical and laboratory features were recorded. The hemagglutination inhibition (HAI) assay was used to define serotype-specific responses. Seroconversion rates varied according to the type of chemotherapy during the vaccination period. In some cases, there was a late rise in titer, suggesting that a wild-type infection had occurred, leading to an estimate of vulnerability of this population. In patients with ALL, responses to the vaccine were greater when it was given early in the course of treatment. We conclude that seroconversion rates are well below the rates cited for the general population. The 3 acute myeloid leukemia patients had a particularly poor response to the vaccine. In the case of ALL patients, it may be possible to adjust the timing of the vaccine to optimize the response.