Association of race and ethnicity with clinical phenotype, genetics, and survival in pediatric acute myeloid leukemia

Blood Advances - Tập 5 - Trang 4992-5001 - 2021
Shannon E. Conneely1, Casey L. McAtee1, Rohit Gupta1, Joseph Lubega1, Michael E. Scheurer1, Rachel E. Rau1
1Department of Pediatrics, Baylor College of Medicine, Houston, TX

Tóm tắt

Abstract

Black and Hispanic children with acute myeloid leukemia (AML) have worse outcomes compared with White children. AML is a heterogeneous disease with numerous genetic subtypes in which these disparities have not been specifically investigated. In this study, we used the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database to examine the association of race-ethnicity with leukemia cytogenetics, clinical features, and survival outcomes within major cytogenetic subgroups of pediatric AML. Compared with White non-Hispanic patients, t(8;21) AML was more prevalent among Black (odds ratio [OR], 2.22; 95% confidence interval [CI], 1.28-3.74) and Hispanic patients (OR, 1.74; 95% CI, 1.05-2.83). The poor prognosis KMT2A rearrangement t(6;11)(q27;q23) was more prevalent among Black patients (OR, 6.12; 95% CI, 1.81-21.59). Among those with KMT2Ar AML, Black race was associated with inferior event-free survival (EFS) (hazard ratio [HR], 2.31; 95% CI, 1.41-3.79) and overall survival (OS) (HR, 2.54; 1.43-4.51). Hispanic patients with KMT2Ar AML also had inferior EFS (HR, 2.20; 95% CI, 1.27-3.80) and OS (HR, 2.07; 95% CI, 1.09-3.93). Similarly, among patients with t(8;21) or inv(16) AML (ie, core-binding factor [CBF] AML), Black patients had inferior outcomes (EFS HR, 1.93; 95% CI, 1.14-3.28 and OS HR, 3.24; 95% CI, 1.60-6.57). This disparity was not detected among patients receiving gemtuzumab ozogamicin (GO). In conclusion, racial-ethnic disparities in survival outcomes among young people with AML are prominent and vary across cytogenetic subclasses. Future studies should explore the socioeconomic and biologic determinants of these disparities.


Tài liệu tham khảo

Winestone, 2019, Disparities in survival and health outcomes in childhood leukemia, Curr Hematol Malig Rep., 14, 179, 10.1007/s11899-019-00515-x Winestone, 2016, The role of acuity of illness at presentation in early mortality in black children with acute myeloid leukemia, Am J Hematol., 92, 141, 10.1002/ajh.24605 Gramatges, 2017, Ethnic disparities relative to disease features and outcomes in children with acute myeloid leukemia, Pediatr Blood Cancer., 64, e26487, 10.1002/pbc.26487 Aplenc, 2006, Ethnicity and survival in childhood acute myeloid leukemia: a report from the Children’s Oncology Group, Blood., 108, 74, 10.1182/blood-2005-10-4004 Li, 2018, Comparable on-therapy mortality and supportive care requirements in Black and White patients following initial induction for pediatric acute myeloid leukemia, Pediatr Blood Cancer., 66, e27583, 10.1002/pbc.27583 Winestone, 2017, Complications preceding early deaths in Black and White children with acute myeloid leukemia, Pediatr Blood Cancer., 64, e26712, 10.1002/pbc.26712 Fisher, 2010, Risk factors for renal failure in pediatric patients with acute myeloid leukemia: a retrospective cohort study, Pediatr Blood Cancer., 55, 655, 10.1002/pbc.22601 Winestone, 2019, Disparities in pediatric acute myeloid leukemia (AML) clinical trial enrollment, Leuk Lymphoma., 60, 2190, 10.1080/10428194.2019.1574002 Gamis, 2014, Gemtuzumab ozogamicin in children and adolescents with de novo acute myeloid leukemia improves event-free survival by reducing relapse risk: results from the randomized phase III Children’s Oncology Group trial AAML0531, J Clin Oncol., 32, 3021, 10.1200/JCO.2014.55.3628 Lange, 2008, Outcomes in CCG-2961, a children’s oncology group phase 3 trial for untreated pediatric acute myeloid leukemia: a report from the children’s oncology group, Blood., 111, 1044, 10.1182/blood-2007-04-084293 Rubnitz, 2006, Effect of race on outcome of white and black children with acute myeloid leukemia: the St. Jude experience, Pediatr Blood Cancer., 48, 10, 10.1002/pbc.20878 Bolouri, 2017, The molecular landscape of pediatric acute myeloid leukemia reveals recurrent structural alterations and age-specific mutational interactions, Nat Med., 24, 103, 10.1038/nm.4439 Health NI of, 2020 Cooper, 2011, AAML03P1, a pilot study of the safety of gemtuzumab ozogamicin in combination with chemotherapy for newly diagnosed childhood acute myeloid leukemia., Cancer., 118, 761, 10.1002/cncr.26190 VanderWeele, 2011, Causal mediation analysis with survival data, Epidemiology., 22, 582, 10.1097/EDE.0b013e31821db37e Lange, 2017, Applied mediation analyses: a review and tutorial, Epidemiol Health., 39, e2017035, 10.4178/epih.e2017035 Therneau, 2020 Team von Elm, 2008, The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies, J Clin Epidemiol., 61, 344, 10.1016/j.jclinepi.2007.11.008 Pollard, 2016, CD33 expression and its association with gemtuzumab ozogamicin response: results from the Randomized Phase III Children’s Oncology Group Trial AAML0531, J Clin Oncol., 34, 747, 10.1200/JCO.2015.62.6846 Pui, 2012, Treatment outcomes in black and white children with cancer: results from the SEER database and St Jude Children’s Research Hospital, 1992 through 2007, J Clin Oncol., 30, 2005, 10.1200/JCO.2011.40.8617 Linabery, 2008, Childhood and adolescent cancer survival in the US by race and ethnicity for the diagnostic period 1975-1999, Cancer., 113, 2575, 10.1002/cncr.23866 Balgobind, 2009, Novel prognostic subgroups in childhood 11q23/MLL-rearranged acute myeloid leukemia: results of an international retrospective study, Blood., 114, 2489, 10.1182/blood-2009-04-215152 Bhatnagar, 2020, Poor survival and differential impact of genetic features of black patients with acute myeloid leukemia, Cancer Discov., 11, 626, 10.1158/2159-8290.CD-20-1579 Winestone, 2018, Increased disease burden among black children compared to white children with newly diagnosed acute myeloid leukemia, Blood., 132, 369, 10.1182/blood-2018-99-120076 Rafiee, 2019, ABCB1 SNP predicts outcome in patients with acute myeloid leukemia treated with Gemtuzumab ozogamicin: a report from Children’s Oncology Group AAML0531 Trial, Blood Cancer J., 9, 51, 10.1038/s41408-019-0211-y Lamba, 2017, CD33 splicing polymorphism determines gemtuzumab ozogamicin response in de novo acute myeloid leukemia: report from Randomized Phase III Children’s Oncology Group Trial AAML0531, J Clin Oncol., 35, 2674, 10.1200/JCO.2016.71.2513 Galanter, 2012, Development of a panel of genome-wide ancestry informative markers to study admixture throughout the Americas, PLoS Genet., 8, e1002554, 10.1371/journal.pgen.1002554 Scheurer, 2018, An overview of disparities in childhood cancer: report on the Inaugural Symposium on Childhood Cancer Health Disparities, Houston, Texas, 2016, Pediatr Hematol Oncol., 35, 95, 10.1080/08880018.2018.1464088 Ogedegbe, 2020, Responsibility of edical journals in addressing racism in health care, JAMA Netw Open., 3, e2016531, 10.1001/jamanetworkopen.2020.16531 Beck, 2020, The color of health: how racism, segregation, and inequality affect the health and well-being of preterm infants and their families, Pediatr Res., 87, 227, 10.1038/s41390-019-0513-6 Zhang, 2019, Differences in stage of cancer at diagnosis, treatment, and survival by race and ethnicity among leading cancer types, JAMA Netw Open., 3, e202950, 10.1001/jamanetworkopen.2020.2950