The timing of cyclic cytotoxic chemotherapy can worsen neutropenia and neutrophilia
Bibliographic record
Abstract
Despite recent advances in immunotherapies, cytotoxic chemotherapy continues to be a first-line treatment option for the majority of cancers. Unfortunately, a common side effect in patients undergoing chemotherapy treatment is neutropenia. To mitigate the risk of neutropenia and febrile neutropenia, prophylactic treatment with granulocyte-colony stimulating factor (G-CSF) is administered. Extensive pharmacokinetic/pharmacodynamic modelling of myelosuppression during chemotherapy has suggested avenues for therapy optimization to mitigate this neutropenia. However, the issue of resonance, whereby neutrophil oscillations are induced by the periodic administration of cytotoxic chemotherapy and the coadministration of G-CSF, potentially aggravating a patient's neutropenic/neutrophilic status, is not well-characterized in the clinical literature. Here, through analysis of neutrophil data from young acute lymphoblastic leukaemia patients, we find that resonance is occurring during cyclic chemotherapy treatment in 26% of these patients. Motivated by these data and our previous modelling studies on adult lymphoma patients, we examined resonance during treatment with or without G-CSF. Using our quantitative systems pharmacology model of granulopoiesis, we show that the timing of cyclic chemotherapy can worsen neutropenia or neutrophilia, and suggest clinically-actionable schedules to reduce the resonant effect. We emphasize that delaying supportive G-CSF therapy to 6-7 days after chemotherapy can mitigate myelosuppressive effects. This study therefore highlights the importance of quantitative systems pharmacology for the clinical practice for developing rational therapeutic strategies.
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| 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".