Citations 1
Cerebrospinal fluid D-2-hydroxyglutarate for IDH-mutant glioma monitoring
Riviere-Cazaux, Cécile , Suzuki, Yuta , Kizilbash, Zain, Laxen, William , Lacey, Jean M., Wipplinger, Tamara , Warrington, Arthur E. , Keough, Michael B. , Kamga, Lionel Fotso, Andersen, Katherine M., Canaday, Nicholas, Kosel, M. L., Tortorelli, Silvia , Ruff, Michael W. , Decker, Paul A, Eckel-Passow, Jeanette E, Kizilbash, Sani H, Laxen, William J, Wipplinger, Tamara M, Decker, Paul A. , Eckel-Passow, Jeanette E , Kaufmann, Timothy J , Burns, Terry C , Kosel, Matthew , Sener, Uğur , Eckel‐Passow, Jeanette E. , Kizilbash, Sani H. , Kaufmann, Timothy J. , Burns, Terry C.
Neuro-Oncology Advances | March 4, 2026 | Volume: 8 | Issue: 1 | Pages: No page available
Abstract Background Imaging-based glioma monitoring is confounded by treatment-related changes. D-2-hydroxyglutarate (D-2-HG), produced by the isocitrate dehydrogenase (IDH) mutation, is detectable in cerebrospinal fluid (CSF), which can be sampled from cranial or lumbar compartments. We evaluated CSF D-2-HG as a serially accessible biomarker for IDH-mutant gliomas, including the optimal compartment for longitudinal sampling. Methods Lumbar and cranial CSF samples were collected from patients with IDH-mutant gliomas or IDH-wild-type central nervous system pathologies via surgical field collection, lumbar punctures, and CSF access devices. CSF D-2-HG was quantified via our CLIA-certified gas chromatography mass spectrometry assay. Results D-2-HG was significantly higher in cranial than lumbar CSF from IDH-mutant glioma patients. Consistent with low D-2-HG abundance in lumbar CSF, lumbar samples could not discriminate IDH-mutant gliomas from IDH-wild-type lesions. In contrast, cranial CSF D-2-HG was significantly higher in IDH-mutant gliomas than wild-type lesions, providing an adequate baseline for initial evaluations of monitoring capabilities. Across 75 samples from 7 consecutive patients with grade 4 IDH-mutant astrocytomas, serial cranial CSF D-2-HG decreased with cytoreduction, remained unchanged with stable disease, and increased with disease progression, but not pseudoprogression. Conclusions Serial cranial CSF D-2-HG shows promise as a monitoring biomarker for IDH-mutant gliomas.