Disparities in Survival and Health Outcomes in Childhood Leukemia
Purpose of Review
The aim of this review is to summarize the current literature on pediatric leukemia disparities with attention to not only racial and ethnic disparities, but also socioeconomic disparities. We focus on disparities in survival as well as other health-related outcomes, including end-of-life care and late effects.
While progress has been made in decreasing some disparities, most notably in pediatric acute lymphoblastic leukemia, disparities along many axes persist. Proposed etiologies include differences in the genomic alterations of the leukemia itself to differences in access to care that operate through socioeconomic status, insurance, and geographic location.
As approaches to therapy become increasingly technical and complex, particular attention to the equitable distribution of these personalized therapeutic interventions is essential. Moving beyond simple descriptive studies to focus on mechanisms of existing disparities will allow for design of interventions to reduce or eliminate disparities in pediatric leukemia.
KeywordsDisparities Leukemia Mortality Survivorship Race/ethnicity
Compliance with Ethical Standards
Conflict of Interest
Lena E. Winestone and Richard Aplenc declare that they have no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 12.• Abrahão R, Lichtensztajn DY, Ribeiro RC, Marina NM, Keogh RH, Marcos-Gragera R, et al. Racial/ethnic and socioeconomic disparities in survival among children with acute lymphoblastic leukemia in California, 1988–2011: a population-based observational study. Pediatr Blood Cancer. 2015;62(10):1819–25. Cohort study in California showing worse survival in minorities and children from the lowest SES neighborhoods with ALL.Google Scholar
- 13.Kahn JM, Cole PD, Blonquist TM, Stevenson K, Jin Z, Barrera S, et al. An investigation of toxicities and survival in Hispanic children and adolescents with ALL: results from the Dana-Farber Cancer Institute ALL consortium protocol 05-001. Pediatr Blood Cancer. 2018;65(3):e26871.CrossRefGoogle Scholar
- 15.•• Petridou ET, Sergentanis TN, Perlepe C, Papathoma P, Tsilimidos G, Kontogeorgi E, et al. Socioeconomic disparities in survival from childhood leukemia in the United States and globally: a meta-analysis. Ann Oncol. 2015;26(3):589–97. Meta-analysis demonstrating increased mortality among ALL patients with low SES at the individual- and area-levels.Google Scholar
- 16.Bona K, Blonquist TM, Neuberg DS, Silverman LB, Wolfe J. Impact of socioeconomic status on timing of relapse and overall survival for children treated on Dana-Farber Cancer Institute ALL consortium protocols (2000-2010). Pediatr Blood Cancer. 2016;63(6):1012–8. https://doi.org/10.1002/pbc.25928.CrossRefGoogle Scholar
- 17.• Wolfson J, Sun C-L, Wyatt L, Stock W, Bhatia S. Adolescents and young adults with acute lymphoblastic leukemia and acute myeloid leukemia: impact of Care at Specialized Cancer Centers on survival outcome. Cancer Epidemiol Biomark Prev. 2017;26(3):312–20. Cohort study in LA County demonstrating a survival benefit to being treated at a specialized cancer center.CrossRefGoogle Scholar
- 18.Pui CH, Pei D, Pappo AS, Howard SC, Cheng C, Sandlund JT, et al. 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. 2012;30(16):2005–12. https://doi.org/10.1200/jco.2011.40.8617.CrossRefGoogle Scholar
- 21.Abrahão R, Keogh RH, Lichtensztajn DY, Marcos-Gragera R, Medeiros BC, Coleman MP, et al. Predictors of early death and survival among children, adolescents and young adults with acute myeloid leukaemia in California, 1988-2011: a population-based study. Br J Haematol. 2016;173(2):292–302. https://doi.org/10.1111/bjh.13944.CrossRefGoogle Scholar
- 22.• Winestone LE, Getz KD, Miller TP, Wilkes JJ, Sack L, Li Y, et al. The role of acuity of illness at presentation in early mortality in black children with acute myeloid leukemia. Am J Hematol. 2017;92(2):141–8. https://doi.org/10.1002/ajh.24605. Cohort study demonstrating that acuity at presentation mediates 61% of excess early mortality in Black pediatric AML patients.CrossRefGoogle Scholar
- 23.Li Y, Newton JG, Getz KD, Huang YS, Seif AE, Fisher BT, et al. Comparable on-therapy mortality and supportive care requirements in Black and White patients following initial induction for pediatric acute myeloid leukemia. Pediatr Blood Cancer. 2019;66(4):e27583. https://doi.org/10.1002/pbc.27583.CrossRefGoogle Scholar
- 24.•• Green AL, Furutani E, Ribeiro KB, Rodriguez-Galindo C. Death within 1 month of diagnosis in childhood cancer: an analysis of risk factors and scope of the problem. J Clin Oncol. 2017;35(12):1320–7. https://doi.org/10.1200/JCO.2016.70.3249. Cohort study using SEER data demonstrating Black and Hispanic patients and patients in lower income counties are at higher risk for early death across multiple pediatric cancers including leukemia.CrossRefGoogle Scholar
- 25.Winestone LE, Getz KD, Rao P, Li Y, Hall M, Huang YV, et al. Disparities in pediatric acute myeloid leukemia (AML) clinical trial enrollment. Leuk Lymphoma. 2019:1–9. https://doi.org/10.1080/10428194.2019.1574002.
- 27.Johnston EE, Muffly L, Alvarez E, Saynina O, Sanders LM, Bhatia S et al. End-of-life care intensity in patients undergoing allogeneic hematopoietic cell transplantation: a population-level analysis. J Clin Oncol. 2018;JCO.2018.78.095.Google Scholar
- 30.•• Liu Q, Leisenring WM, Ness KK, Robison LL, Armstrong GT, Yasui Y, et al. Racial/ethnic differences in adverse outcomes among childhood cancer survivors: the childhood cancer survivor study. J Clin Oncol. 2016;34(14):1634–43. Cohort study showing Black pediatric cancer survivors have higher all-cause mortality, attirbutable to SES, and higher risk of diabetes and cardiac conditions.CrossRefGoogle Scholar
- 34.Taylor OA, Brown AL, Brackett J, Dreyer ZE, Moore IK, Mitby P, et al. Disparities in neurotoxicity risk and outcomes among pediatric acute lymphoblastic leukemia patients. Clin Cancer Res. 2018;24(20):5012–7.Google Scholar
- 36.Polite BN, Adams-Campbell LL, Brawley OW, Bickell N, Carethers JM, Flowers CR, et al. Charting the future of cancer health disparities research: a position statement from the American Association for Cancer Research, the American Cancer Society, the American Society of Clinical Oncology, and the National Cancer Institute. CA Cancer J Clin. 2017;67(5):353–61.CrossRefGoogle Scholar
- 38.Bhatia S. A comprehensive approach to improve medication adherence in pediatric ALL. Children’s Oncology Group; ClinicalTrials.gov Identifier: NCT01503632.
- 39.• Bhatia S, Landier W, Hageman L, Kim H, Chen Y, Crews KR, et al. 6MP adherence in a multiracial cohort of children with acute lymphoblastic leukemia: a Children’s Oncology Group study. Blood. 2014;124(15):2345–53. https://doi.org/10.1182/blood-2014-01-552166. Prospective cohort study identifying poor adherence to oral chemotherapy among Black and Asian Americans and implicating adherence as a mediator of relapse in ALL.CrossRefGoogle Scholar
- 40.Tasian S. A phase 2 study of ruxolitinib with chemotherapy in Children with acute lymphoblastic leukemia. Children’s Oncology Group; ClinicalTrials.gov Identifier: NCT02723994.
- 41.Harvey RC, Mullighan CG, Chen I-M, Wharton W, Mikhail FM, Carroll AJ, et al. Rearrangement of CRLF2 is associated with mutation of JAK kinases, alteration of IKZF1, Hispanic/Latino ethnicity, and a poor outcome in pediatric B-progenitor acute lymphoblastic leukemia. Blood. 2010;115(26):5312–21.CrossRefGoogle Scholar
- 48.Bhojwani D, Sposto R, Shah NN, Rodriguez V, Yuan C, Stetler-Stevenson M, et al. Inotuzumab ozogamicin in pediatric patients with relapsed/refractory acute lymphoblastic leukemia. Leukemia. 2018.Google Scholar