Computed tomography quantification of body adiposity and induction outcomes in patients with newly diagnosed acute lymphoblastic leukemia

Abstract

Abstract Background Obesity is encountered in up to 40% of children and adolescents who initiate acute lymphoblastic leukemia (ALL) therapy (Ghosh et al. Canc Med 2013). This association has also been encountered in older adults, in whom five-year mortality rates were higher in obese than non-obese patients (Liu et al. Blood Canc. 2021). Furthermore, previous studies have observed adverse outcomes and toxicity in patients with obesity and ALL such as in the CALGB 10403 (C10403) study, in which worse survival was seen in patients with a higher body mass index (BMI). Although BMI is frequently used to measure body composition, computed tomography (CT) allows for quantification of visceral (VA) and subcutaneous adiposity (SA) as it may help link adipose composition with induction outcomes. With the rising rates of obesity and adoption of regimens containing asparaginase, we investigated the impact of adipose on the safety and efficacy of induction in adult patients with newly diagnosed ALL. Methods This retrospective analysis included adult patients with newly diagnosed ALL who were treated at City of Hope (COH) and received pegaspargase as part of their induction regimen. CT scans at baseline prior to induction were used for analysis of SA and VA tissue. This was semiautomatically performed at the level of the second lumbar vertebra using the Fat Analysis tool by TeraRecon. A threshold of -150 to -50 Hounsfield Units (HU) was applied to the single axial CT image slice, and the boundaries of fat were manually adjusted to ensure accurate segmentation. The objective was to assess high grade hepatotoxicity (grade >3 transaminitis and/or hyperbilirubinemia), hyperglycemia, measurable residual disease (MRD), and complete remission (CR) rates. Statistical analysis was done with descriptive statistics, Mann Whitney U test, Pearson chi-squared test, and univariate analysis (UVA) logistic regression analysis (p-value < 0.05). Results There were 55 patients that met the inclusion criteria for analysis. The median age for the whole cohort was 31 years (range 18-63), and majority were males (56.4%), and Hispanics (73%). The most common ALL phenotype was B-ALL (69.1%) and B-ALL subtype was Ph-like (36.9%). The median BMI was 28.5 (range 17.6-52) with 47% having BMI >30. Median (Range) of VA (cm2) and SA (cm2) was 106 (2-317) and 171 (1.1-663) respectively. The median (Range) of VA/SA ratio was 0.49 (0.03-2.9), with 61.8% having V/S > 0.4. Hepatic steatosis was found in 33.3% (n=17) of patients at baseline. C10403 (83.6%) induction was frequently used with the median (range) pegaspargase dose being 3750 international units (IU) (700-5400). The CR/CRi and post induction MRD negativity rate amongst responders was 91% and 50% respectively. The rate of grade >3 hepatotoxicity, grade > 3 hyperglycemia, and all grade hyperglycemias were: 30.9%, 23.6% and 49.1% respectively. When comparing Ph-like vs non-Ph-like B-ALL, patients with Ph-like ALL had significantly higher median VA (197 vs 96.9; p=0.04) despite similar median BMI (33 vs 31; p=0.19). Although remission rates were similar between groups, MRD negativity rates were lower in Ph-like ALL (25% vs 60.9%; p=0.04). Rates of all grade hyperglycemia were higher in the Ph-like cohort (78.6% vs 41.7%; p=0.02), with half (50%) requiring insulin during induction. Univariate (UVA) logistic regression analysis identified association of BMI >30 (p=0.02), and VA > 100 (p=0.003) with a higher risk of grade >3 hepatotoxicity. Additionally, UVA showed that higher VA (>150) (p=0.025), Ph-like (p=0.045), and BMI >30 (p=0.04) was associated with lower rates of MRD negative remission post induction. Conclusions Among adult patients receiving induction with pegaspargase-containing pediatric-type regimen, higher VA as assessed by CT imaging was associated with higher risk of high-grade hepatotoxicity, hyperglycemia and lower rates of MRD negativity after induction. Higher VA was more frequently encountered in Ph-like ALL patients among whom the majority were of Hispanic/Latino origin, representing a specific association of this high-risk ALL subtype with visceral adiposity. Future studies and novel interventions including lifestyle and pharmaceutical therapies are warranted in this patient population and could improve induction outcomes and disease response as previously shown in other populations such as in the IDEAL study (Orgel et al. Blood Adv 2021).