Dose-Related Effect of Chemotherapy on Bone Mineral Density Among Pediatric Acute Lymphoblastic Leukemia Survivors.

OBJECTIVES: Reduced bone mineral density (BMD) can negatively affect lifelong skeletal health by -increasing the risk for developing osteopenia and osteoporosis. This study evaluated the relationship between BMD and cumulative doses of intravenous (IV) methotrexate (MTX) and glucocorticoids in pediatric acute lymphoblastic leukemia (ALL) survivors. The association between BMD and vitamin D concentrations measured at the time of entry into the long-term follow-up program was also assessed. METHODS: This retrospective study included pediatric ALL survivors who had received a dual-energy X-ray absorptiometry (DXA) scan after the end of therapy (EOT) or within the 6 months prior to the EOT. Low/-intermediate and high cumulative IV MTX doses were defined as doses less than 20,000 mg/m2 and -greater than or equal to 20,000 mg/m2, respectively. Descriptive statistics, Student t test, and linear -regression were used to analyze the data. RESULTS: A total of 62 patients, with 34 patients in the low/intermediate and 28 patients in the high -cumulative IV MTX dose groups, were analyzed. The median time from EOT to DXA scan was 2.3 years. The mean DXA lumbar spine z score was significantly lower in the high cumulative IV MTX dose group -compared with the low/intermediate dose group (-0.86 vs -0.14; p = 0.008). Cumulative glucocorticoid doses and vitamin D concentrations were not associated with BMD. CONCLUSIONS: Pediatric patients who had received cumulative IV MTX doses of greater than or equal to 20,000 mg/m2 during their ALL treatment had lower BMD than those who had received lower cumulative doses.

Tumor Genomic Profiling and Ex Vivo Drug Sensitivity Testing for Pediatric Leukemia and Lymphoma Patients.

OBJECTIVE: To describe the frequency of use of tumor genomic profiling and functional ex vivo drug sensitivity testing in pediatric patients with hematologic malignancies at our institution, and to determine how the results affected treatment selection. METHODS: A retrospective chart review was conducted to analyze the frequency of tumor genomic profiling and functional drug sensitivity screening in our institution in pediatric patients with hematologic malignancies and to ask if the results were used to direct treatment. A case series of patients for whom these testing recommendations resulted in therapeutic interventions is reported. RESULTS: Thirty-three patients underwent tumor genomic profiling assays, functional ex vivo testing, or both. Nineteen patients (58%) had genomic profiling assays performed alone, 3 (9%) had functional ex vivo testing performed alone, and 11 (33%) had both tests performed. Twenty-one (64%) patients had potentially actionable mutations detected by the genomic profiling assay. Seven (21%) patients received at least 1 chemotherapeutic agent in accordance with the tumor genomic profiling or functional ex vivo drug sensitivity testing results. Three (43%) of the 7 patients who were treated with testing directed therapy had a favorable treatment response (PR or CR) to treatments selected based upon results of genomic or functional ex vivo testing. CONCLUSIONS: This retrospective case series demonstrates that precision medicine techniques such as genomic profiling and drug sensitivity testing can positively inform treatment selection in pediatric patients with relapsed or refractory leukemia and lymphoma.