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

Winestone, Lena E.; Getz, Kelly; Miller, Tamara P.; Wilkes, Jennifer J.; Sack, Leah; Li, Yimei; Huang, Yuan‐Shung; Seif, Alix E.; Bagatell, Rochelle; Fisher, Brian T.; Epstein, Andrew J.; Aplenc, Richard

doi:10.1002/ajh.24605

Cited by 35 publications

(55 citation statements)

References 43 publications

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“…The difference in age distribution observed among those patients who died is consistent with our previous finding that age is a confounder in the association between race and mortality. 9 Importantly, a number of the White patients who died had congenital heart disease or prematurity, while the profile of preexisting conditions for Black patients who died included asthma and autism (Table S1). The two most common causes of death in AML are hemorrhage and infection.…”

Section: Discussionmentioning

confidence: 99%

“…Early deaths have previously been associated with low performance status, French–American–British type M4 and M5, hyperleukocytosis, thrombocytopenia, and older age . We recently demonstrated that induction mortality among Black children with AML was more than twice that of White children . This disparity was associated with increased frequency of multiorgan system failure and increased requirement for Intensive Care Unit (ICU) level resources within 72 hr of initial admission.…”

Section: Introductionmentioning

confidence: 99%

“…4,8 We recently demonstrated that induction mortality among Black children with AML was more than twice that of White children. 9 This disparity was associated with increased frequency of multiorgan system…”

Section: Introductionmentioning

confidence: 99%

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Complications preceding early deaths in Black and White children with acute myeloid leukemia

Winestone

Getz

Miller

et al. 2017

Pediatric Blood & Cancer

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Black patients have a twofold increased risk of induction mortality compared to White patients with acute myeloid leukemia (AML). We reviewed diagnosis and billing data from Pediatric Health Information System for 28 AML Induction I deaths to investigate conditions preceding death in White and Black patients. Half of deaths occurred within 10 days of initial diagnostic admission. Respiratory, cardiac, renal, and infectious complications were common prior to both White and Black deaths. Deaths in White patients were more commonly preceded by intracranial hemorrhage compared to deaths in Black patients. Future studies should assess management approaches of complications by race to identify modifiable processes that reduce mortality.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Complications preceding early deaths in Black and White children with acute myeloid leukemia

Winestone

Getz

Miller

et al. 2017

Pediatric Blood & Cancer

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“…Patient characteristics included age, sex, insurance type (private, public, or other), and time period of diagnosis (2004–2009 vs 2010–2014). ICU‐level resource utilization during the first 72 hours following admission for initial AML chemotherapy was also included as a covariate, where the timeframe was chosen a priori to evaluate clinical acuity at presentation rather than acuity resulting from chemotherapy toxicity . Acuity of presentation was categorized into three groups (none, 1 system, and ≥2 systems) based on the number of organ systems requiring ICU‐level resources within the first 72 hours of the diagnostic admission.…”

Section: Methodsmentioning

confidence: 99%

“…Each of these mechanisms may be relevant at different points in the treatment and posttreatment trajectory. Our previous study focused on early mortality in the initial induction period and the role of acuity at presentation . This study demonstrated that black patients have higher acuity prior to initiating chemotherapy, which substantially contributed to higher mortality during induction I.…”

Section: Introductionmentioning

confidence: 95%

Comparable on‐therapy mortality and supportive care requirements in Black and White patients following initial induction for pediatric acute myeloid leukemia

Newton

Getz

et al. 2018

Pediatric Blood & Cancer

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Background Black patients with acute myeloid leukemia (AML) are more likely to present with high acuity and consequently experience higher rates of induction mortality than white patients. Given the consistently identified racial disparities in overall survival (OS) among patients with AML, we aimed to evaluate whether there were sustained on‐therapy racial differences in inpatient mortality, intensive care unit (ICU) requirements, or supportive care beyond initial induction. Procedure Within a retrospective cohort of 1239 children diagnosed with AML between 2004 and 2014 in the Pediatric Health Information System (PHIS) database who survived their initial course of induction chemotherapy, we compared on‐therapy inpatient mortality, ICU‐level care requirements, treatment course duration, cumulative length of hospital stay (LOS), and resource utilization after induction I by race. Results Over the period from the start of induction II through completion of frontline chemotherapy, there were no significant differences in mortality (adjusted odds ratios [OR], 1.01; 95% confidence intervals [CI], 0.41–2.48), ICU‐level care requirements (adjusted OR, 0.93; 95% CI, 0.69–1.26), LOS (adjusted mean difference, 3.2 days; 95% CI, −2.3–9.6), or supportive care resource utilization for black patients relative to white patients. Course‐specific analyses also demonstrated no differences by race. Conclusion Although black patients have higher acuity at presentation and higher induction mortality, such disparities do not persist over subsequent frontline chemotherapy treatment. This finding allows interventions aimed at reducing disparities to be directed at presentation and induction.

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Pharmacogenomics, Race, and Treatment Outcome in Pediatric Acute Myeloid Leukemia

Lamba,

Marrero,

et al. 2024

JAMA Netw Open

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ImportanceDisparities in outcomes exist between Black and White patients with acute myeloid leukemia (AML), with Black patients experiencing poorer prognosis compared with their White counterparts.ObjectiveTo assess whether varying intensity of induction therapy to treat pediatric AML is associated with reduced disparities in treatment outcome by race.Design, Setting, and ParticipantsA comparative effectiveness analysis was conducted of 86 Black and 359 White patients with newly diagnosed AML who were enrolled in the AML02 trial from 2002 to 2008 or the AML08 trial from 2008 to 2017. Statistical analysis was conducted from July 2023 through January 2024.InterventionsPatients in AML02 were randomly assigned to receive standard low-dose cytarabine-based induction therapy or augmented high-dose cytarabine-based induction therapy, whereas patients in AML08 received high-dose cytarabine-based therapy.Main Outcomes and MeasuresCytarabine pharmacogenomic 10–single-nucleotide variant (ACS10) scores were evaluated for association with outcome according to race and treatment arm.ResultsThis analysis included 86 Black patients (mean [SD] age, 8.8 [6.5] years; 54 boys [62.8%]; mean [SD] leukocyte count, 52 600 [74 000] cells/µL) and 359 White patients (mean [SD] age, 9.1 [6.2] years; 189 boys [52.6%]; mean [SD] leukocyte count, 54 500 [91 800] cells/µL); 70 individuals with other or unknown racial and ethnic backgrounds were not included. Among all patients without core binding factor AML who received standard induction therapy, Black patients had significantly worse outcomes compared with White patients (5-year event-free survival rate, 25% [95% CI, 9%-67%] compared with 56% [95% CI, 46%-70%]; P = .03). By contrast, among all patients who received augmented induction therapy, there were no differences in outcome according to race (5-year event-free survival rate, Black patients, 50% [95% CI, 38%-67%]; White patients, 48% [95% CI, 42%-55%]; P = .78). Among patients who received standard induction therapy, those with low ACS10 scores had a significantly worse 5-year event-free survival rate compared with those with high scores (42.4% [95% CI, 25.6%-59.3%] and 70.0% [95% CI, 56.6%-83.1%]; P = .004); however, among patients who received augmented induction therapy, there were no differences in 5-year event-free survival rates according to ACS10 score (low score, 60.6% [95% CI, 50.9%-70.2%] and high score, 54.8% [95% CI, 47.1%-62.5%]; P = .43).Conclusions and RelevanceIn this comparative effectiveness study of pediatric patients with AML treated in 2 consecutive clinical trials, Black patients had worse outcomes compared with White patients after treatment with standard induction therapy, but this disparity was eliminated by treatment with augmented induction therapy. When accounting for ACS10 scores, no outcome disparities were seen between Black and White patients. Our results suggest that using pharmacogenomics parameters to tailor induction regimens for both Black and White patients may narrow the racial disparity gap in patients with AML.

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

Cited by 35 publications

References 43 publications

Complications preceding early deaths in Black and White children with acute myeloid leukemia

Complications preceding early deaths in Black and White children with acute myeloid leukemia

Comparable on‐therapy mortality and supportive care requirements in Black and White patients following initial induction for pediatric acute myeloid leukemia

Pharmacogenomics, Race, and Treatment Outcome in Pediatric Acute Myeloid Leukemia

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