Investigating Ethnic Differences In Toxicities Of Childhood All Therapy

Introduction Acute lymphoblastic leukemia (ALL) is the most common childhood cancer with an excellent survival rate due to advancements in therapy. However, significant chemotherapy treatment-related toxicities (TRTs) are associated with the intensity of such treatments, which can affect quality of life, preclude the ability to provide optimal therapy, and impact survival. Further, outcomes are worse among certain minority populations, including Hispanic patients. At this single institution with a predominately Hispanic population, we sought to review several TRTs and determine whether Hispanic ethnicity may be a risk factor for increased severe, short-term TRTs and to explore the effects of TRTs on event-free survival (EFS). Methods This study is a retrospective chart-review of patients diagnosed with ALL at Children9s Hospital Los Angeles from January 2008 to December 2010. Infants, patients with Down9s syndrome and those who transferred to another institution during therapy were excluded from this study. Demographic and TRT information were collected from the electronic medical record, from the start of treatment until 30 days after the end of primary therapy, relapse, transplant, or death. TRTs were graded per the Common Terminology Criteria for Adverse Events version 4.0; only toxicities severe enough to negatively effect patients9 quality of life, chemotherapy continuation, and survival were included. The specific TRTs were fractures, osteonecrosis, and peripheral neuropathy of ≥ grade 2, fungal and culture-positive bacterial infections, thrombosis, pancreatitis, and hyperbilirubinemia ≥ grade 3, and hepatic transaminitis ≥ grade 4. The X 2 test was used to compare the proportions of Hispanic and non-Hispanic patients with and without the selected TRTs. Univariable and multivariable Cox regression models were used to examine the association of patient demographics with EFS and time to TRT. All analyses were performed using a 2-sided test and completed using the statistical software Stata. Results Of the 172 patients diagnosed with ALL between 2008 and 2010, 138 patients are included in this study, 124 with B-cell ALL and 14 with T-cell ALL. Among the 138 patients, 57.2% were male, 24.6% were obese, 76.1% were Hispanic, and 58% were classified as high-risk by the NCI Rome criteria. The median age at diagnosis was 7.9 years (range 1.1 to 20). All patients were treated according to ongoing Children9s Oncology Group therapeutic studies. During the course of therapy, 23 patients relapsed, 3 developed secondary malignancy, and 2 patients died from infection. There were 156 TRTs observed in 85 patients, with 61.6% of patients experiencing one or more of the selected TRTs. The most common TRTs were infectious and gastrointestinal/hepatobiliary events. While Hispanic patients had 2.2 times higher frequency of pancreatitis than non-Hispanic patients and 1.8 times more hyperbilirubinemia, there were no statistically significant differences in the incidence of any TRTs by ethnicity. NCI high risk and older age were the only significant predictors of any TRT (p Discussion In this relatively small cohort of patients, we did not identify ethnicity as a risk factor for increased TRTs during therapy for ALL, although certain TRTs such as pancreatitis and hyperbilirubinemia may be more common among Hispanic patients. As expected, Hispanic ethnicity, NCI risk, and age at diagnosis were risk factors for increased relapse and death. These results may suggest that additional factors, such as genetics, disease biology, or medication compliance, may play a more significant role in worse outcomes for Hispanic patients, rather than difference in tolerance of the treatment itself. Analyses of a larger cohort of patients are ongoing to confirm these results and to comprehensively analyze the determinants of pancreatitis and hepatic toxicity, and their interaction with obesity in Hispanic patients with ALL. Disclosures Bhojwani: Amgen: Other: Blinatumumab global pediatric advisory board 2015.