How to Improve Survival for Pediatric Leukemia Patients

UCSF studies uncover effects of pre-conception smoking and racial disparities in pediatric leukemias

By Melinda Krigel

It is well known that tobacco smoke adversely affects the prognosis of adult cancers, including myeloid leukemia. But less is known about the effects in children. Now, researchers at UC San Francisco and UC Berkeley are investigating the impact of pre- and post-natal exposures to tobacco smoke on the survival rate of children with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML).

Leukemia is the most common childhood cancer comprised mainly of ALL followed by AML. Despite improvements in cancer survival, leukemia incidence has increased in recent decades in the United States, especially in the Latinx population and significant disparities persist by socioeconomic status (SES), race and ethnicity. Exposures to tobacco smoke from fathers before conception and from secondhand smoke after birth have been associated with increased risks of developing childhood ALL and AML. Yet minimal attention has been given to the possible impact of tobacco smoke on survival following leukemia diagnosis.

In a study published recently in Cancer Epidemiology, Biomarkers & Prevention, the UCSF research team showed that paternal preconception smoking decreased 5-year survival in children with AML.

The researchers evaluated whether pre- and post-natal exposures to tobacco smoke decreased 5-year survival of 1,235 childhood ALL and 188 childhood AML cases derived from a population-based case-control study in California. The patients were diagnosed between 1995 and 2015 (with a median follow-up time of 13.2 years). They analyzed data for tobacco smoking before conception, during pregnancy and after birth. The researchers also looked at parental education and income, clinical features and vital status through 2020, and also adjusted for sociodemographic characteristics and risk group (for ALL only).

About 23% of mothers and 39% of fathers reported smoking and 130 children with ALL and 52 with AML died within 5 years. For AML, increased risks of death were observed among children whose fathers smoked before conception compared to non-smoking fathers. It was observed that paternal preconception smoking may also reduce 5-year survival among ALL cases with particular molecular subtypes.

“As oncologists, knowing your patients’ history of tobacco smoke exposure is important so that it can be integrated into prognostic discussions regarding childhood leukemias,” said Lena Winestone, MD, senior author and UCSF assistant professor, specializing in pediatric malignancies. “At a minimum, primary care doctors can counsel families about the risks related to smoking in the pre-natal period for the health of future children.”

More likely to require ICU-level care

In another study, published Nov. 3, 2023 in Pediatric Blood and Cancer, Winestone and her team explored racial and ethnic disparities in acuity among children with acute leukemia. Across acute leukemia types, first-line chemotherapy treatment carries the highest mortality and complications are substantially more common in patients with AML than ALL.

The researchers previously found that children with AML who required intensive care for multiorgan system failure at diagnosis had a 14 times higher risk of dying during the initial treatment phase compared with those not requiring such intervention. Black patients were more likely to require intensive care unit (ICU)-level resources at initial presentation compared with white patients.

However, after accounting for intensive care treatment within the first 72 hours of initial admission, the researchers found no racial differences in continued use of ICU-level resources during first line treatment or in subsequent chemotherapy. This finding suggested that clinical status in the peri-diagnostic period drives disparities in early mortality and overall survival in AML. In contrast, despite persistence of racial and ethnic disparities in ALL survival, induction mortality disparities have not been observed in recent clinical trials.

The researchers studied the cases of 899 patients with acute leukemia diagnosed at two large children's hospitals, and evaluated disparities in disease burden, organ dysfunction, vital signs and timing of therapy in children newly presenting with acute leukemia. They examined (EHR) data regarding racial, ethnic and socioeconomic status (SES) differences in presenting clinical severity and management to assess potential contributions to survival disparities. They hypothesized that Black patients were more likely to both present with abnormal vital signs and have abnormal labs within the first 72 hours following admission.

Black patients with AML had increased prevalence of elevated white blood cell count and uric acid; Black patients with ALL demonstrated increased prevalence of coagulopathy (prolonged or excessive bleeding). Black patients’ presentation more frequently included multiple lab abnormalities consistent with advanced physiologic dysfunction. No differences were found in days to therapy initiation or vital signs at presentation.

“Our study demonstrated that high disease burden at presentation of newly diagnosed AML is more prevalent in Black children than non-Hispanic white children,” said study first author Winestone. “Black patients also have a greater than 2-fold risk of presenting with substantial dysfunction in multiple systems across acute leukemia types. Together these findings start to identify the factors that drive racial disparities in early death and highlight the need for interventions to address access to care for children with leukemia.”

For the tobacco exposure study:

Funding: The research was supported by the California Tobacco-Related Disease Research Program (TRDRP) grant #T31IP1502. Collection and/or maintenance of the original CCLS data were partly supported by the National Institute of Environmental Health Sciences (NIEHS) grants #P42ES004705, R01ES009137, and R24ES028524, and the UK Children with Cancer grant #2006/052.

Additional authors: Please see the study.

For the Racial and ethnic disparities study:

Funding: Alex’s Lemonade Stand Foundation for Childhood Cancer, an American Society of Hematology Scholar Award, and an American Cancer Society (CSDG-21-093-01-HOPS)

Additional authors: Please see the study.

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