Advertisement

Current Hematologic Malignancy Reports

, Volume 14, Issue 3, pp 179–186 | Cite as

Disparities in Survival and Health Outcomes in Childhood Leukemia

  • Lena E. WinestoneEmail author
  • Richard Aplenc
Health Economics (N Khera, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Health Economics

Abstract

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.

Recent Findings

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.

Summary

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.

Keywords

Disparities Leukemia Mortality Survivorship Race/ethnicity 

Notes

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.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Linabery AM, Ross JA. Trends in childhood cancer incidence in the U.S. (1992-2004). Cancer. 2008;112(2):416–32.CrossRefGoogle Scholar
  2. 2.
    Hunger SP, Lu X, Devidas M, Camitta BM, Gaynon PS, Winick NJ, et al. Improved survival for children and adolescents with acute lymphoblastic leukemia between 1990 and 2005: a report from the Children’s Oncology Group. J Clin Oncol. 2012;30(14):1663–9.CrossRefGoogle Scholar
  3. 3.
    Braveman PA, Kumanyika S, Fielding J, Laveist T, Borrell LN, Manderscheid R, et al. Health disparities and health equity: the issue is justice. Am J Public Health. 2011;101(Suppl 1):S149–55.CrossRefGoogle Scholar
  4. 4.
    Gravlee CC. How race becomes biology: embodiment of social inequality. Am J Phys Anthropol. 2009;139(1):47–57.CrossRefGoogle Scholar
  5. 5.
    Burchard EG, Ziv E, Coyle N, Gomez SL, Tang H, Karter AJ, et al. The importance of race and ethnic background in biomedical research and clinical practice. N Engl J Med. 2003;348(12):1170–5.CrossRefGoogle Scholar
  6. 6.
    Galobardes B, Shaw M, Lawlor DA, Lynch JW, Davey Smith G. Indicators of socioeconomic position. J Epidemiol Community Health. 2006;60(1):7–12.CrossRefGoogle Scholar
  7. 7.
    Kilbourne AM, Switzer G, Hyman K, Crowley-Matoka M, Fine MJ. Advancing health disparities research within the health care system: a conceptual framework. Am J Public Health. 2006;96(12):2113–21.CrossRefGoogle Scholar
  8. 8.
    Pollock BH, DeBaun MR, Camitta BM, Shuster JJ, Ravindranath Y, Pullen DJ, et al. Racial differences in the survival of childhood B-precursor acute lymphoblastic leukemia: a Pediatric Oncology Group Study. J Clin Oncol. 2000;18(4):813–23.CrossRefGoogle Scholar
  9. 9.
    Bhatia S, Sather HN, Heerema NA, Trigg ME, Gaynon PS, Robison LL. Racial and ethnic differences in survival of children with acute lymphoblastic leukemia. Blood. 2002;100(6):1957–64.  https://doi.org/10.1182/blood-2002-02-0395.CrossRefGoogle Scholar
  10. 10.
    Kadan-Lottick NS, Ness KK, Bhatia S, Gurney JG. Survival variability by race and ethnicity in childhood acute lymphoblastic leukemia. JAMA. 2003;290(15):2008–14.  https://doi.org/10.1001/jama.290.15.2008.CrossRefGoogle Scholar
  11. 11.
    Goggins WB, Lo FFK. Racial and ethnic disparities in survival of US children with acute lymphoblastic leukemia: evidence from the SEER database 1988–2008. Cancer Causes Control. 2012;23(5):737–43.CrossRefGoogle Scholar
  12. 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. 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
  14. 14.
    Yang JJ, Cheng C, Devidas M, Cao X, Fan Y, Campana D, et al. Ancestry and pharmacogenomics of relapse in acute lymphoblastic leukemia. Nat Genet. 2011;43(3):237–41.CrossRefGoogle Scholar
  15. 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. 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. 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. 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
  19. 19.
    Seif AE, Fisher BT, Li Y, Torp K, Rheam DP, Huang Y-SV, et al. Patient and hospital factors associated with induction mortality in acute lymphoblastic leukemia. Pediatr Blood Cancer. 2014;61(5):846–52.CrossRefGoogle Scholar
  20. 20.
    Aplenc R, Alonzo TA, Gerbing RB, Smith FO, Meshinchi S, Ross JA, et al. Ethnicity and survival in childhood acute myeloid leukemia: a report from the Children’s Oncology Group. Blood. 2006;108(1):74–80.  https://doi.org/10.1182/blood-2005-10-4004.CrossRefGoogle Scholar
  21. 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. 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. 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. 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. 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.
  26. 26.
    Johnston EE, Alvarez E, Saynina O, Sanders L, Bhatia S, Chamberlain LJ. Disparities in the intensity of end-of-life care for children with cancer. Pediatrics. 2017;140(4):e20170671.CrossRefGoogle Scholar
  27. 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
  28. 28.
    Bona K, Wolfe J. Disparities in pediatric palliative care: an opportunity to strive for equity. Pediatrics. 2017;140(4):e20171662.CrossRefGoogle Scholar
  29. 29.
    Mertens AC, Liu Q, Neglia JP, Wasilewski K, Leisenring W, Armstrong GT, et al. Cause-specific late mortality among 5-year survivors of childhood cancer: the childhood cancer survivor study. JNCI Journal of the National Cancer Institute. 2008;100(19):1368–79.CrossRefGoogle Scholar
  30. 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
  31. 31.
    Chao C, Xu L, Bhatia S, Cooper R, Brar S, Wong FL, et al. Cardiovascular disease risk profiles in survivors of adolescent and young adult (AYA) cancer: the Kaiser Permanente AYA Cancer Survivors Study. J Clin Oncol. 2016;34(14):1626–33.CrossRefGoogle Scholar
  32. 32.
    Getz KD, Sung L, Ky B, Gerbing RB, Leger KJ, Leahy AB, et al. Occurrence of treatment-related cardiotoxicity and its impact on outcomes among children treated in the AAML0531 clinical trial: a report from the Children’s Oncology Group. J Clin Oncol. 2019;37(1):12–21.CrossRefGoogle Scholar
  33. 33.
    Fisher BT, Zaoutis TE, Leckerman KH, Localio R, Aplenc R. Risk factors for renal failure in pediatric patients with acute myeloid leukemia: a retrospective cohort study. Pediatr Blood Cancer. 2010;55(4):655–61.  https://doi.org/10.1002/pbc.22601.CrossRefGoogle Scholar
  34. 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
  35. 35.
    Oeffinger KC, Mertens AC, Sklar CA, Kawashima T, Hudson MM, Meadows AT, et al. Chronic health conditions in adult survivors of childhood cancer. N Engl J Med. 2006;355(15):1572–82.CrossRefGoogle Scholar
  36. 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
  37. 37.
    Corbie-Smith G, St George DMM, Moody-Ayers S, Ransohoff DF. Adequacy of reporting race/ethnicity in clinical trials in areas of health disparities. J Clin Epidemiol. 2003;56(5):416–20.CrossRefGoogle Scholar
  38. 38.
    Bhatia S. A comprehensive approach to improve medication adherence in pediatric ALL. Children’s Oncology Group; ClinicalTrials.gov Identifier: NCT01503632.
  39. 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. 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. 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
  42. 42.
    El-Cheikh J, Crocchiolo R, Furst S, Bramanti S, Sarina B, Granata A, et al. Unrelated cord blood compared with haploidentical grafts in patients with hematological malignancies. Cancer. 2015;121(11):1809–16.CrossRefGoogle Scholar
  43. 43.
    Joshua TV, Rizzo JD, Zhang M-J, Hari PN, Kurian S, Pasquini M, et al. Access to hematopoietic stem cell transplantation: effect of race and sex. Cancer. 2010;116(14):3469–76.CrossRefGoogle Scholar
  44. 44.
    Maude SL, Laetsch TW, Buechner J, Rives S, Boyer M, Bittencourt H, et al. Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. N Engl J Med. 2018;378(5):439–48.CrossRefGoogle Scholar
  45. 45.
    von Stackelberg A, Locatelli F, Zugmaier G, Handgretinger R, Trippett TM, Rizzari C, et al. Phase I/phase II study of blinatumomab in pediatric patients with relapsed/refractory acute lymphoblastic leukemia. J Clin Oncol. 2016;34(36):4381–9.CrossRefGoogle Scholar
  46. 46.
    Kantarjian H, Stein A, Gökbuget N, Fielding AK, Schuh AC, Ribera J-M, et al. Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia. N Engl J Med. 2017;376(9):836–47.CrossRefGoogle Scholar
  47. 47.
    Kantarjian HM, DeAngelo DJ, Stelljes M, Martinelli G, Liedtke M, Stock W, et al. Inotuzumab ozogamicin versus standard therapy for acute lymphoblastic leukemia. N Engl J Med. 2016;375(8):740–53.CrossRefGoogle Scholar
  48. 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
  49. 49.
    Bach PB. National coverage analysis of CAR-T therapies - policy, evidence, and payment. N Engl J Med. 2018;379(15):1396–8.CrossRefGoogle Scholar
  50. 50.
    Penner LA, Dovidio JF, Gonzalez R, Albrecht TL, Chapman R, Foster T, et al. The effects of oncologist implicit racial bias in racially discordant oncology interactions. J Clin Oncol. 2016;34(24):2874–80.CrossRefGoogle Scholar
  51. 51.
    Johnson TJ, Winger DG, Hickey RW, Switzer GE, Miller E, Nguyen MB, et al. Comparison of physician implicit racial bias toward adults versus children. Acad Pediatr. 2017;17(2):120–6.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Division of Allergy, Immunology, and BMT, Department of PediatricsUniversity of California San Francisco (UCSF) Benioff Children’s HospitalSan FranciscoUSA
  2. 2.Helen Diller Family Comprehensive Cancer CenterUCSFSan FranciscoUSA
  3. 3.Division of OncologyThe Children’s Hospital of PhiladelphiaPhiladelphiaUSA
  4. 4.Department of PediatricsUniversity of Pennsylvania School of MedicinePhiladelphiaUSA

Personalised recommendations