Hispanic children most likely to have leukemia treatment intolerance

Acute lymphoblastic leukemia (ALL) is a type of cancer that affects blood and bone marrow. It is the most commonly diagnosed cancer among children, but with timely, focused treatment, there is a good chance it can be cured. Not all children respond well to ALL treatment, however, and researchers now feel they understand one of the reasons why.

SEE ALSO: Hispanic children most at risk for acute leukemia

According to new data from St. Jude Children’s Research Hospital in Memphis, Tennessee, genetic variants may make some ALL patients intolerant of commonly used medications in the treatment process. What’s more, Hispanic children and Asian children are the most likely to have those genetic variations.

A report from Medscape indicates mercaptopurine is the drug of choice for treating ALL patients, but a variant of the gene NUDT15 causes some patients to be intolerant of the standard dose. These patients must often have doses decreased by as much as 50 percent before treatment can be administered. As expected, this can impact ALL therapy, complicating or preventing recovery.

The importance of the variant of NUDT15 & ALL

The risk variant of NUDT15 was found in in 9.8 percent of patients with East Asian ancestry and 3.9 percent of patients with Hispanic ancestry, with much lower rates of occurrence in patients of African or European heritage. The discovery is important, as recent studies also indicate Hispanic children are genetically at a higher risk for ALL compared to non-Hispanic white children.

Now, not only are Hispanic children more likely to develop ALL, they are more likely to be intolerant of common treatments. The data is not as clear-cut as it seems, however.

The findings suggest race/ethnicity can play a role in ALL treatment, but the NUDT15 variant is not unique to Hispanics and Asians, just more common than among other groups. What’s more, there are other genetic variants that also contribute to ALL medication intolerance, and these, such as variants in the TPMT gene, are not as specific to ancestry.

“The effect of the NUDT15 variants on mercaptopurine toxicity is impressive — on par with risk factors that are clinically used to guide mercaptopurine therapy,” first author Jun J. Yang, PhD told Medscape. “We do not know yet what the exact actions should be for patients who carry the NUDT15 risk variant. This is the subject of our ongoing research.”

In a press release that accompanied the study from St. Jude’s, researchers indicated more research is needed before intolerance to ALL drugs can be completely attributed to the variants uncovered. The data suggests individuals of Asian heritage, for example, likely have other genetic factors that influence medication sensitivity.

SEE ALSO: Gene variation common to Hispanics linked to high-risk pediatric leukemia

“Although the higher prevalence of NUDT15 variant in East Asians may have contributed to over-representation of mercaptopurine intolerance in this population, we also acknowledge that our statistical power was limited by the relatively small number of East Asian patients included in this study,” the researchers wrote. “In addition, East Asian genetic ancestry remained associated with mercaptopurine dose intensity after adjusting for rs166855232, suggesting the existence of other Asian-specific factors related to mercaptopurine sensitivity.”

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