Low Leukocyte MGMT Accompanies Temozolomide-Induced Myelotoxicity in Brain Tumor Patients
Bibliographic record
Abstract
Objective: The methylating agent temozolomide (TMZ) has markedly improved clinical outcome for patients with glioblastoma and other gliomas. While TMZ has comparatively low systemic toxicity, a minority of patients experience severe myelotoxicity that compromises TMZ treatment, necessitating dose reductions and treatment delays. These limitations emphasize the need to develop markers to identify individuals susceptible to TMZ-induced myelosuppression. The purpose of this small pilot study is to examine the association between treatment-limiting myelosuppression in primary brain tumor patients receiving TMZ and expression of O6-methylguanine-DNA methyltransferase (MGMT) in peripheral blood leukocytes (PBL). MGMT is the sole human activity that removes TMZ-induced, cytotoxic O6-methylguanine adducts from DNA. Methods: MGMT biochemical activity and MGMT promoter methylation status, a surrogate measure of MGMT expression, were assayed in PBL from 10 patients who experienced treatment-limiting myelotoxicity during TMZ therapy, 8 patients who experienced no myelotoxicity during TMZ treatment, and 10 disease-free, untreated controls. Results: MGMT activity was detectable in all 28 PBL samples, and all displayed an unmethylated promoter indicative of MGMT expression. Mean PBL MGMT activity was 2-fold lower in patients who experienced myelotoxicity compared to patients without myelotoxicity (8.9 ± 3.9 vs. 18 ± 8.1 fmol/106 cells; P 0.015) and to untreated controls (8.9 ± 3.9 vs. 16 ± 6.8 fmol/106 cells; P 0.015). Conclusions: These preliminary data indicate that low MGMT activity in PBL is associated with myelotoxicity in primary brain tumor patients receiving TMZ, and may have value if confirmed in a larger study as a marker to identify patients at greater risk of treatment-limiting myelosuppression.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".