Disparities in Incidence and Mortality of Childhood Leukemias

Judith Shanika Pelpola


This paper analyzes socioeconomic and racial disparities in incidence and mortality of acute lymphoblastic and acute myeloid leukemia, the two most common leukemias in children. Several reports have shown higher incidences of childhood leukemias in those of higher socioeconomic status, but higher mortality in those of lower socioeconomic status. Proposed reasons for this include reduced access to proper diagnosis and non-adherence to treatment for those of low socioeconomic status. A similar trend is observed in racial disparities in childhood leukemias, with higher incidences of leukemias in Hispanics and whites and higher mortality rates in minorities, including Hispanics and blacks. Studies have suggested genetics, daycare attendance, language barriers, and treatments reactions to be primary factors in these disparities. By analyzing these proposed reasons and possible underlying mechanisms, this paper finds many target areas for policies that can reduce disparities, both socioeconomic and racial, in childhood leukemias. Key areas to address include under-diagnosis in lower income and minority communities, regulation of environmental hazards in lower income and minority communities, and reducing language barriers and other forms of institutionalized racism amongst others. Further research is needed to fully understand the underlying mechanisms of disparities in childhood leukemias. Doing so will help policy makers better able to combat these disparities and eventually reduce overall incidence and improve prognosis of both acute lymphoblastic and acute myeloid leukemia.

I. Introduction

The most common cancer in children, leukemia accounts for approximately 30% of all childhood cancers, affecting roughly 3500 children every year in the US alone.1 The two most common form of leukemia in children is acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). In leukemia, white blood cells undergo random genetic mutations, which cause them to become malignant, weakening the immune system and making children more prone to serious infection. While certain biological markers are inheritable and can predispose a child to getting leukemia, the disease itself is not inheritable. Special tests including bone marrow aspirations, complete blood counts, and lymph node biopsies are needed to diagnose childhood leukemias. Treatment ranges from chemotherapy to bone marrow transplants.

Socioeconomic and racial disparities in childhood leukemias exist in many stages of the disease from diagnosis to treatment. Several reports showed that those of higher socioeconomic status have higher incidence rates of childhood leukemias than those of low socioeconomic status. Studies also report higher mortality and relapse rates in those of lower socioeconomic status. Regarding racial disparities, Hispanics have the highest incidence rates, followed by non-Hispanic whites and Asians, and the lowest being that of blacks. Studies also showed that minority patients have a significantly higher mortality rate than non-Hispanic whites. This paper seeks to examine and suggest reasons for reported trends in socioeconomic and racial disparities in relation to childhood leukemias. Doing so may help highlight feasible and effective ways to help reduced socioeconomic and racial disparities in childhood leukemias.


II. Disparities Due to Socioeconomic Status

Low socioeconomic status is often correlated with poorer health status, which is often explained in terms of material deprivation and allostatic load. Material deprivation can include lack of education, which can affect treatment understanding and adherence, or limited access to preventative care. Allostatic load is associated with psychological stressors. Regarding incidences of childhood leukemias, studies have shown the disease is more common in those of higher socioeconomic status (SES), while survival rates of childhood leukemias are lower among those of lower SES.


A. Disparities in Incidences of Childhood Leukemia

For many years, childhood leukemias was thought to be more prevalent in those of higher SES. A study of childhood leukemias incidence in England and Wales from 1976-2005 revealed a higher incidence of childhood leukemias in more affluent communities.2 The findings were surprising because low socioeconomic status has been traditionally correlated with poor health status, as demonstrated by the Whitehall study, which found that those of lower occupational status, a common measure of SES, had poorer health independent of access to healthcare.3

The authors of the study suggested that incidences of childhood leukemias in lower SES communities might go unreported. The study found little change in the strength of this association over the 30-year period, suggesting under-diagnosis rather than under-recording of childhood leukemias is the reason for the seen pattern in childhood leukemias incidence. One reason for this is lack of resources in under-privileged communities. For example, the lack of a nearby pediatric hospital may mean fewer doctors in the area with expertise in diagnosing childhood leukemias, which requires specialized testing. This can also result in children dying from infection without ever being diagnosed. Failure to diagnose may result in a “lower” incidence rate in lower SES communities. A second study used information from the United Kingdom Childhood Cancer Study to reevaluate the findings of the England and Wales study. This study found no correlation between SES and ALL incidences in the UK.4 However, the study also cautioned that incidence in lower SES communities may have been higher than seen due to under-diagnosis.

Studies of the links between traffic density and childhood leukemias showed higher incidences in higher density areas. Southern California children living within 250 yards of high traffic density areas, such as major streets or freeways, were approximately 8 times as likely to get leukemia, particularly AML.5 High-density areas are correlated with lower income neighborhoods. While neighborhood SES cannot give definitive information on individual SES, this study does show the effect of living in a low SES neighborhood on childhood leukemias incidences. Another study done in Italy found that individual socioeconomic status did not change risk significantly compared to traffic density, suggesting little independent effect of individual SES.6 Overall, incidence may be higher in lower SES communities due in part to environmental risk factors, but these cases may go undiagnosed.


B. Disparities in Prognosis, Relapse, and Mortality of Childhood Leukemia

Mortality trends of childhood leukemias show higher rates of mortality in patients of lower individual and neighborhood socioeconomic status. In 2007, researchers looking at mortality rates of childhood leukemias in Brazil found higher mortality in developing states.7 Though overall, mortality has decreased across the country, the majority of these decreases are concentrated in developed states, suggesting better health care access. The study looked at 127 children with leukemia who were deemed eligible for clinical trial and found that those of lower socioeconomic status received less information regarding the specifics of the trials than those of higher SES, resulting in a lower participation rate in this population. Those of lower SES were also more likely to abandon treatment. This was also seen in a 2011 study of treatment plans conducted by researchers at the University of York. The first phase of treatment for childhood leukemias is typically nine months of hospitalization, usually involving high dose chemotherapy or radiation.8 Afterwards, children are treated on an outpatient basis. Researchers found children of low SES had a higher risk of mortality due to difficulty in complying with home treatment. Furthermore, children may look healthier after primary treatment (i.e. no infections), which may be interpreted by those with limited knowledge, such as those of lower SES, as no longer requiring treatment, resulting in non-adherence to home therapy.

The above observations can contribute to social anomie, the loss of trust in society, due to a failure to give fair and equal treatment to all individuals regardless of SES status.9 Social anomie can further perpetuate non-adherence, establishing a positive feedback loop that increases mortality for those of lower SES and widens social disparities in childhood leukemias prognosis and mortality. A 1999 study of ALL in Brazil cited socioeconomic status as one of the strongest predictors of relapse in childhood ALL.10 Researchers concluded, “poor prognosis for leukemic children of low SES is just another indicator of social inequality.” Thus, poor prognosis, relapse rates, and mortality are linked to lower socioeconomic status due to differences in handling low SES patients, which reflect continuing social inequality.


C. Does Socioeconomic Status Affect Access to Treatment?

Treatment access has a significant impact on disparities in childhood leukemias mortality. In the 2007 Brazil study, researchers also found a widening gap of treatment technology and improvement between resource-rich countries worldwide and resource-poor countries.11 Lower SES neighborhoods may not have pediatric hospitals, which can affect both diagnosis and treatment.12 Improvements in treatment can be costly and are typically more accessible to those of higher SES. This phenomenon is seen in many health conditions in the United States, which outspends most countries in medical technology yet has consistently lower average life expectancies until the age of 80.13 Improvements in medical technology benefit those who can afford it, leaving many with significant health issues, lowering the average life expectancy. According to Steven Schroeder, this is consistent with a prevailing national will that associates good health with middle and upper classes.14 This suggests that access to treatment is linked to both material deprivation and, more importantly, an emphasis on the health of middle and upper class patients over that of lower class patients.


III. Disparities Due to Race/Ethnicity, Independent of SES

Incidence and mortality from childhood leukemias is highest amongst minorities, perhaps due to genetic differences, behavioral factors, and social factors, including residential segregation, concentrated poverty and violence, and high allostatic load.15

A. Disparities in Incidences of Childhood Leukemia

Ongoing research aims to determine why Hispanic children have the highest incidence rate of childhood leukemias.16 A 2005 study of children in northern and central California noted that fewer Hispanic children attended daycare,17 which has been associated with increased exposure to infections and lower risk of leukemia. However, the study also noted that daycare attendance lowered risk of ALL in white children, but not in Hispanic children, suggesting potential biological differences as well.

These genetic differences may be important factor in differential distribution of leukemia. A 2012 study found racial differences in the frequency of the risk allele for the ARID5B gene, which is associated with ALL.18 Hispanics had a higher frequency of the risk allele than non-Hispanic whites, with the lowest frequency in blacks, matching the racial distribution of leukemia. Deletions in glutathione s-transferase genes, such as GSTM1 and GSTT1, were correlated with risk of ALL.19 Lacking both GSTM1 and GSTT1 was found to be more common in black ALL patients than white ALL patients, suggesting this “double –null” genotype along with an additional, perhaps environmental, factor increased risk of ALL in blacks. Such a combination may not be significant in ALL incidence in non-Hispanic whites. Overall, it seems that behavioral and genetic factors may both play significant roles in racial incidence patterns of childhood leukemias.


B. Disparities in Prognosis, Relapse, and Mortality of Childhood Leukemia

Racial trends in prognosis, relapse, and mortality of childhood leukemias are similar to socioeconomic trends, with minority populations having higher relapse and mortality rates. Blacks and Hispanics have up to a 12% and 17% higher risk of mortality from childhood leukemias than non-Hispanic whites respectively.22 According to a study in 2000 comparing mortality rates in black and Hispanic children, part of mortality disparities was attributable to biological prognostic markers, such as a B-precursor, which were more found more in blacks and Hispanics.23 Researchers also found differences in chemotherapy drug metabolism based on race and ethnicity, especially in relation to chemotherapy drugs MTX and 6-MP. This suggests a significant biological component in racial disparities in mortality of childhood leukemias.

Native Americans were also shown to have the highest rate of mortality and a greater risk of relapse among all racial and ethnic groups.24 Controlling for SES factors related to race by offering free treatment for patients, a study conducted at St. Jude Children’s Research Hospital found that the high-risk PDE4B allele was most predominant in those with Native American ancestry. This allele is correlated with sensitivity to medications used to treat ALL, particularly glucocorticoids, resulting in higher relapse and mortality risk. The study also found that an additional round of chemotherapy mitigated the effects of having the PDE4B risk allele. A similar genetic mechanism may also explain sensitivity of blacks and Hispanics to chemotherapy drugs.

Non-adherence to treatment also plays a significant role in racial disparities in childhood leukemias mortality. In a study of ALL patients undergoing home therapy with mercaptopurine, researchers found Hispanic children were more likely than non-Hispanic white children to skip doses of mercaptopurine, resulting in a lower survival.25 A possible reason for this is a language barrier, which can decrease understanding of the disease and result in non-adherence.

Language difference also plays a part in mortality rates in East Asian patients. A 2012 study found significantly poorer ALL survival rates in East Asian children compared to non-Hispanic whites. However, East Asians are comparable to non-Hispanic whites in socioeconomic status and education.27 Because of this, researchers suggested language difference as a significant factor in survival rates. Overall, both biological and behavioral differences seem to explain racial disparities independent of socioeconomic status in prognosis, relapse, and mortality of childhood leukemias.


IV. Conclusion

It is clear that both socioeconomic and racial or ethnic factors play significant roles in childhood leukemias disparities. Understanding the mechanisms by which these disparities exist is key to implementing policies that can help mitigate socioeconomic and racial disparities. The following conclusions and suggestions are but a small step in this direction.

1) Persistent under-diagnosis of childhood leukemias in low socioeconomic communities results in an incidence pattern favoring those of higher socioeconomic status. Therefore, increasing the number pediatric hospitals or clinics in low SES neighborhoods can increase proper diagnosis of childhood leukemias at earlier stages, resulting in better overall prognosis.

2) The correlation of high traffic density and higher risk of childhood leukemias contributes to childhood leukemias incidences in low SES communities. Reducing pollution by using cleaner fuels may help reduce this risk.

3) Because patients of lower SES receiving less information than those of high SES appears to be a significant factor in prognosis and mortality rates in lower SES communities, it is important to encourage doctors to fully explain all treatment options, regardless of an individual’s ability to pay. Increasing access to more treatment options can help mitigate the effects of social anomie experienced by those of lower SES.

4) Certain genetic risk factors such as PDE4B and ARID5B are more common in particular racial and ethnic groups. However, failing to check for these factors in other groups can result in later diagnoses and worse prognoses. Therefore, diagnosis and treatment should be based on the patient’s own genetic markers instead of using race as a proxy for genetics. Race is in many ways a social construct. Analyzing a patient’s genome also gives a more accurate understanding of potential complications and reactions to different treatments.

5) Language barriers have a significant effect on mortality in childhood leukemias. Having readily available translators, especially for doctors’ appointments can help reduce the effect of language barriers. This can help the patient’s family be more involved in the treatment process, and lower non-adherence in minority patients.

6) Racial discrimination and stereotyping may have an effect on non-adherence and treatment access in minority groups. While this is not easily fixed, standardizing diagnostic testing for childhood leukemias across different races may help mitigate racial disparities.

In conclusion, more complete testing of a child’s genetic markers as well as an understanding of limitations due to socioeconomic status and race can help physicians develop more personalized treatment plans, which give the child the best chance to survive. In the long run, reduction of social inequality and negative perception of poor and minority communities will be essential to reduction of disparities in childhood leukemias.

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