First name
Dana
Middle name
M
Last name
Walker

Title

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

Year of Publication

2014

Number of Pages

846-52

Date Published

2014 May

ISSN Number

1545-5017

Abstract

<p><strong>BACKGROUND: </strong>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.</p>

<p><strong>PROCEDURE: </strong>We performed a retrospective cohort analysis of 8,516 children ages 0 to &lt;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.</p>

<p><strong>RESULTS: </strong>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).</p>

<p><strong>CONCLUSIONS: </strong>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.</p>

DOI

10.1002/pbc.24855

Alternate Title

Pediatr Blood Cancer

PMID

24249480

Title

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

Year of Publication

2014

Number of Pages

112-20

Date Published

02/2014

ISSN Number

1529-7535

Abstract

<p><strong>OBJECTIVE: </strong>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.</p>

<p><strong>DESIGN: </strong>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.</p>

<p><strong>SETTING: </strong>Forty-three children's hospitals contributing data to the Pediatric Health Information System database.</p>

<p><strong>PATIENTS: </strong>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.</p>

<p><strong>INTERVENTIONS: </strong>None.</p>

<p><strong>MEASUREMENTS AND MAIN RESULTS: </strong>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 &lt; 0.0001).</p>

<p><strong>CONCLUSIONS: </strong>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.</p>

DOI

10.1097/PCC.0000000000000042

Alternate Title

Pediatr Crit Care Med

PMID

24366507

Title

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

Year of Publication

2013

Number of Pages

1916-23

Date Published

05/2013

ISSN Number

1097-0142

Abstract

<p><strong>BACKGROUND: </strong>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.</p>

<p><strong>METHODS: </strong>The Pediatric Health Information System database was used to identify children treated for presumed de novo AML between 1999 and 2010. Induction mortality, risk factors for induction mortality, and resource utilization by induction regimen were estimated using standard frequentist statistics, logistic regression, and Poisson regression, respectively.</p>

<p><strong>RESULTS: </strong>A total of 1686 patients were identified with an overall induction case fatality rate of 5.4% that decreased from 9.8% in 2003 to 2.1% in 2009 (P = .0023). The case fatality rate was 9.0% in the intensively timed DCTER (dexamethasone, cytarabine, thioguanine, etoposide, and rubidomycin [daunomycin]/idarubicin) induction and 3.8% for ADE (cytarabine, daunomycin, and etoposide) induction (adjusted odds ratio = 2.2, 95% confidence interval = 1.1-4.5). Patients treated with intensively timed DCTER regimens had significantly greater antibiotic, red cell/platelet transfusion, analgesic, vasopressor, renal replacement therapy, and radiographic resource utilization than patients treated with ADE regimens. Resource utilization was substantially higher than reported in published pediatric AML clinical trials.</p>

<p><strong>CONCLUSIONS: </strong>Induction mortality for children with AML decreased significantly as ADE use increased. In addition to higher associated mortality, intensively timed DCTER regimens had a correspondingly higher use of health care resources. Using resource utilization data as a proxy for adverse events, adverse event rates reported on clinical trials substantially underestimated the clinical toxicities of all pediatric AML induction regimens.</p>

DOI

10.1002/cncr.27957

Alternate Title

Cancer

PMID

23436301

Title

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.

Year of Publication

2013

Number of Pages

616-20

Date Published

04/2013

ISSN Number

1545-5017

Abstract

<p><strong>BACKGROUND: </strong>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).</p>

<p><strong>PROCEDURE: </strong>We conducted a retrospective cohort study to describe patterns of dexrazoxane use in pediatric patients with ALL or AML using the Pediatric Health Information Systems (PHIS) database. Patients identified as having de novo ALL and AML at these PHIS hospitals were included.</p>

<p><strong>RESULTS: </strong>Of 8,733 patients with ALL and 2,556 with AML, 207 (2.4%) and 52 (2.0%) received dexrazoxane, respectively. Dexrazoxane use was greater in older children with ALL and AML and in black patients and males with ALL. Dexrazoxane use varied across time and by region in ALL, but not in AML. Prescribing practices differed across institutions and most patients received the first dose early or late after the start of leukemia treatment.</p>

<p><strong>CONCLUSIONS: </strong>Dexrazoxane administration is limited in patients with ALL and AML and prescribing practices vary across the country. Further work is necessary to understand how dexrazoxane is used in patients at highest risk of developing cardiotoxicity and to define its true effect on the development of SMNs.</p>

DOI

10.1002/pbc.24270

Alternate Title

Pediatr Blood Cancer

PMID

22948886

Title

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

Year of Publication

2015

Number of Pages

704-9

Date Published

04/2015

ISSN Number

1545-5017

Abstract

<p><strong>BACKGROUND: </strong>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.</p>

<p><strong>PROCEDURE: </strong>A retrospective cohort of children with newly identified malignancies (excluding AML) receiving anthracyclines between January 1, 1999 and March 31, 2011 was established using the Pediatric Health Information System (PHIS). Patients were followed for all subsequent admissions to identify dexrazoxane exposures and secondary AML, defined by AML ICD-9 codes and AML induction chemotherapy. Logistic regression was used to model the association of dexrazoxane and secondary AML risk. A propensity score was used to adjust for measurable confounding.</p>

<p><strong>RESULTS: </strong>Of 15,532 patients in the cohort exposed to anthracyclines, 1,406 received dexrazoxane. The secondary AML rate was 0.21% (3 of 1,046) in dexrazoxane-exposed and 0.55% (77 of 14,126) in unexposed patients. In a propensity score-adjusted multivariate analysis, dexrazoxane exposure was not associated with an increased risk of secondary AML, OR = 0.38, 95% CI 0.11-1.26.</p>

<p><strong>CONCLUSIONS: </strong>Dexrazoxane was not associated with an increased risk of secondary AML in a large cohort of pediatric cancer patients receiving anthracyclines in US hospitals. While these data support dexrazoxane's safety in the general pediatric oncology population, additional studies are needed to confirm these findings and to quantify dexrazoxane's long-term cardioprotective effects.</p>

DOI

10.1002/pbc.25043

Alternate Title

Pediatr Blood Cancer

PMID

24668949

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