Abstract 2349: Comparison of the blood, bone marrow, and cerebrospinal fluid metabolomes in children with acute leukemia

Abstract

Abstract Background: Children with acute leukemia (AL) are at risk for relapse, treatment toxicity, second neoplasms, and death. Understanding host and tumor response to therapy is necessary to achieve high survival rates and minimize adverse effects. Metabolomics, the characterization of small molecules in a biological system, may be useful for monitoring treatment response. In support of this, we previously identified metabolites in bone marrow (BM) plasma associated with end-induction minimal residual disease (MRD) and in cerebrospinal fluid (CSF) associated with fatigue. Because procedures for obtaining BM and CSF are invasive and subject patients to risk, we sought to determine whether the BM and CSF metabolomes of children undergoing therapy for AL were correlated with the blood metabolome. Methods: Blood plasma, BM, and CSF were collected at the end-induction from 11 patients with newly diagnosed AL treated at Texas Children's Hospital (Houston, TX). Global metabolomic profiling was performed by Metabolon (Durham, NC), using liquid chromatography-tandem mass spectrometry according to published methods. We assessed the number and type (e.g. lipid, amino acid) of metabolites in each sample. For each metabolite identified in ≥2 samples from ≥2 patients, we computed Spearman rank correlation coefficients to estimate the pairwise correlations between blood, BM, and CSF. Results: Patients were predominantly male (N=7) and Latino (N=9). Ten were diagnosed with B-cell acute lymphoblastic leukemia and one with mixed phenotype acute leukemia. Among 670 metabolites detected in ≥2 blood and BM plasma samples, 370 (58%) demonstrated moderate to strong correlations (Spearman's rho ≥0.5) and 317 (47%) were significant at p<0.05. Among 340 metabolites detected in ≥2 blood and CSF samples, 135 (40%) demonstrated moderate to strong correlations and 96 (28%) were significant at p<0.05. Among 318 metabolites detected in ≥2 BM plasma and CSF samples, 88 (28%) demonstrated moderate to strong correlations and 66 (21%) were significant at p<0.05. We observed generally moderate to strong correlations between BM and blood for 19 metabolites we previously reported were associated with MRD (median rho 0.51, interquartile range 0.24-0.69). We observed a strong positive correlation between CSF and blood for one of three metabolites we previously reported were associated with fatigue (dimethylglycine, rho=0.7, p=0.02), and a moderate inverse correlation for a second (gamma-glutamylglutamine, rho=-0.51, p=012). Conclusions: There is substantial correlation between the blood and BM plasma metabolomes at end-induction among children with ALL, including metabolites putatively associated with early treatment response. Correlations between CSF and blood or BM plasma are weaker, implying that the CSF metabolome is distinct. The blood plasma metabolome may approximate the BM but not CSF metabolome in children with ALL. Citation Format: Jeremy M. Schraw, J.P. Woodhouse, Melanie B. Bernhardt, Olga A. Taylor, Terzah M. Horton, Michael E. Scheurer, Mehmet F. Okcu, Karen R. Rabin, Philip J. Lupo, Austin L. Brown. Comparison of the blood, bone marrow, and cerebrospinal fluid metabolomes in children with acute leukemia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2349.