Fractures Higher in Non-Hispanic Patients Treated for Newly Diagnosed Pediatric ALL

Non-Hispanic children with newly diagnosed ALL displayed higher fracture rates.
Non-Hispanic children with newly diagnosed ALL displayed higher fracture rates.

ORLANDO, FLFractures, osteonecrosis, and opportunistic infections all occurred at higher incidences in non-Hispanic children undergoing treatment for newly diagnosed acute lymphoblastic leukemia (ALL), according to research presented at the 57th American Society of Hematology (ASH) Annual Meeting.1

Prior studies have identified that Hispanic ethnicity is associated with higher risk of relapse and reduced overall survival,  said Justine Kahn, MD, of Morgan Stanley Children's Hospital of NewYork-Presbyterian, Columbia University Medical Center in New York, NY. However, “studies comparing the incidence of treatment-related toxicities between Hispanic and non-Hispanic patients have not been previously reported,” she added.

The goal of this study was to “compare the incidence of treatment-related toxicities in Hispanic and non-Hispanic children and adolescents undergoing therapy for newly diagnosed ALL,” Dr. Kahn said.

The retrospective cohort study investigated incidence of treatment-related toxicities associated with corticosteroids, which includes serious infection (bacterial and opportunistic) and bony morbidities, and to asparaginase, which includes pancreatitis, allergy and anaphylaxis, and thrombosis.

Ethnicity of each patient was designated at the time of study enrollment by a clinical research associate.

Between 2005 and 2011, 794 children and adolescents aged 1 to 18 years were enrolled in the study and 730 were evaluable, 150 Hispanic (18%) and 580 non-Hispanic (73%); 64 did not have ethnicity documented. No significant difference in disease-risk group, age, or gender was observed between the two groups. Weight was significantly higher in Hispanic patients (31.9 ± 24.4 kg) than in non-Hispanic patients (26.9 ± 18.7 kg; P = .021).

Results showed that “the overall incidence of fracture in all patients was 14.5% and was significantly higher in non-Hispanic patients (6% in Hispanic and 16.7% in non-Hispanic, P < .001),” Dr. Kahn said. Overall incidence of osteonecrosis was 8.9%; this was significantly higher in non-Hispanic patients (10.3%) compared with non-Hispanic patients (3.3%; P = .007).

“Non-Hispanic patients had significantly higher rates of opportunistic infection (Pneumocystis pneumonia) than Hispanic patients (0.7% in Hispanic and 4% in non-Hispanic, P = .041),” she said. However, no significant difference in overall incidence of infection was observed between the 2 groups (42% in Hispanic and 50% in non-Hispanic, P = .081). “A similar difference in the incidence of bacteremia between the 2 groups approached, but did not reach, statistical significance (P = .052),” she said.

No significant difference was observed between Hispanic and non-Hispanic patients in incidence of asparaginase-related toxicities, and “there was no significant difference in overall incidence of infection between the 2 groups (42% in Hispanic and 50% in non-Hispanic, P = .081),” Dr. Kahn said.

When examined by ethnicity, 5-year overall survival was 89.2% among Hispanic patients vs 92.4% among non-Hispanic patients (P = .0254); similarly, 5-year disease-free survival was 82.4% among the Hispanic and 90.5% among the non-Hispanic cohort (P = .009).

“The risk for, and impact of, therapy-related toxicities varies by a patient's treatment tolerance; perhaps as a function of age and gender or as a result of disease biology or genetic polymorphisms affecting drug metabolism,” she said.

For example, optimal drug exposure may be affected by biologic factors such as pharmacogenomics or tolerance, or non-biologic factors, such as adherence, comorbidities, and nutrition. In turn, optimal drug exposure may affect disease-free survival and treatment-related toxicities.

External designation of ethnicity was noted as a study limitation. Future studies will have patients self-report ethnicity, Dr. Kahn said.

Reference

1. Kahn J, Barrera S, Davila R, et al. Higher Incidence of Treatment-Related Toxicities in Non-Hispanic Patients Undergoing Therapy for Newly Diagnosed Pediatric Acute Lymphoblastic Leukemia on Dana-Farber Cancer Institute ALL Consortium Protocol 05-001. Oral presentation at: 57th American Society of Hematology (ASH) Annual Meeting; December 6, 2015, Orlando, FL.

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