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The role of acuity of illness at presentation in early mortality in black children with acute myeloid leukemia.

ABSTRACT: Black patients with acute myeloid leukemia (AML) experience higher mortality than White patients. We compared induction mortality, acuity of illness prior to chemotherapy, and insurance type between Black and White patients to assess whether acuity of presentation mediates the disparity. Within a retrospective cohort of 1,122 children with AML treated with two courses of standard induction chemotherapy between 2004 and 2014 in the Pediatric Health Information System (PHIS) database, the association between race (Black versus White) and inpatient mortality during induction was examined. Intensive Care Unit (ICU)-level resource utilization during the first 72 hours following admission for initial AML chemotherapy was evaluated as a potential mediator. The total effect of race on mortality during Induction I revealed a strong association (unadjusted HR 2.75, CI: 1.18, 6.41). Black patients had a significantly higher unadjusted risk of requiring ICU-level resources within the first 72 hours after initial presentation (17% versus 11%; RR 1.52, CI: 1.04, 2.24). Mediation analyses revealed the indirect effect of race through acuity accounted for 61% of the relative excess mortality during Induction I. Publicly insured patients experienced greater induction mortality than privately insured patients regardless of race. Black patients with AML have significantly greater risk of induction mortality and are at increased risk for requiring ICU-level resources soon after presentation. Higher acuity amongst Black patients accounts for a substantial portion of the relative excess mortality during Induction I. Targeting factors affecting acuity of illness at presentation may lessen racial disparities in AML induction mortality.

SUBMITTER: Winestone LE

PROVIDER: S-EPMC5733783 | biostudies-other | 2017 Feb

REPOSITORIES: biostudies-other

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The role of acuity of illness at presentation in early mortality in black children with acute myeloid leukemia.

Winestone Lena E LE Getz Kelly D KD Miller Tamara P TP Wilkes Jennifer J JJ Sack Leah L Li Yimei Y Huang Yuan-Shung YS Seif Alix E AE Bagatell Rochelle R Fisher Brian T BT Epstein Andrew J AJ Aplenc Richard R

American journal of hematology 20161207 2

Black patients with acute myeloid leukemia (AML) experience higher mortality than White patients. We compared induction mortality, acuity of illness prior to chemotherapy, and insurance type between Black and White patients to assess whether acuity of presentation mediates the disparity. Within a retrospective cohort of 1,122 children with AML treated with two courses of standard induction chemotherapy between 2004 and 2014 in the Pediatric Health Information System (PHIS) database, the associat ...[more]

PMID: 27862214

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Project description:Activity of the enzyme thiopurine methyltransferase (TPMT) determines the anti-leukemic effect of thiopurines used in the chemotherapy of acute lymphoblastic leukemia (ALL) and acute myeloblastic leukemia (AML). TPMT status and its effects on treatment outcome have been studied extensively in ALL and autoimmune disorders, but few data is available on TPMT in AML. The present study assessed the genetic polymorphisms and activity of TPMT in children with AML at different treatment stages, and compared the results with those obtained for children with ALL. The study included 33 children with AML (0.7-19.7 years) treated with 6-thioguanine (6-TG) according to the AML-BFM 2004 Protocol. Blood samples were collected at diagnosis, during and following maintenance chemotherapy from 8, 10 and 17 patients with AML (the assay was performed at two time points in 2 patients), respectively. Blood samples from 105 children with ALL were obtained at diagnosis, during the maintenance chemotherapy and following the cessation of the chemotherapy from 16, 55 and 34 children, respectively. The activity of TPMT in red blood cells lysates was measured using an enzymatic reaction based on the conversion of 6-mercaptopurine into 6-methylmercaptopurine, involving S-adenozyl-L-methionine as the methyl group donor. TPMT mutations were determined using a polymerase chain reaction/restriction fragment length polymorphism method. Median TPMT activity at diagnosis, during maintenance chemotherapy and following chemotherapy was 43.1, 47,3 and 41.7 nmol 6-mMP g-1 Hb h-1, respectively. All patients with AML exhibited the homozygous TPMT*1/*1 genotype, with the exception of 1, who was a heterozygote with the TPMT*1/*3C genotype and demonstrated a TPMT activity level at diagnosis of 42.5 nmol 6-mMP g-1 Hb h-1. At each chemotherapy stage, the median TPMT activities in children with AML were significantly increased compared with the median TPMT activities in children with ALL. The preliminary results suggest that the TPMT activity in AML may be increased compared with that in ALL. Comprehensive studies on the association between thiopurine metabolism and treatment outcome in AML are required, with regard to the cytogenetic and molecular factors currently used for AML risk stratification.

Dataset Information

The role of acuity of illness at presentation in early mortality in black children with acute myeloid leukemia.

Publications

The role of acuity of illness at presentation in early mortality in black children with acute myeloid leukemia.

Similar Datasets

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