Severe Toxicity during Chemotherapy Treatment for Pediatric Acute Myeloid Leukemia
Bibliographic record
Abstract
Treatment for pediatric acute myeloid leukemia (AML) is highly intensive, and thus almost all patients will experience severe toxicities, which are often life-threatening. In 5–10% of patients, treatment for pediatric AML is fatal. To minimize the adverse effects of treatment, identification and characterization of risk factors for severe toxicity is important. Furthermore, toxic and leukemic responses could be related, and it is likely that toxic response is associated with treatment outcome. The focus of this thesis is to describe the severe toxicities occurring during pediatric AML treatment, investigate potential risk factors and describe prophylactic measures and their safety. In addition, we aimed to investigate how toxicity and risk factors for toxicity are related to treatment outcome. The studies in the thesis are based on three different cohorts. Study I is based on a cohort of children diagnosed with AML in the five Nordic countries and Hong Kong. For study II, the cohort was expanded to include children diagnosed in the Netherlands, Belgium, Canada, and the USA. The cohort for studies III and IV was the same: Children diagnosed with AML in the Nordic countries, Hong Kong, Belgium, and the Netherlands. In study I, we found that 90% of children had experienced grade 3–4 toxicities. Overweight and older age were associated with increased risk of severe toxicity. In study II, we found no significant differences in risk of relapse and death for four bodymass index (BMI) groups, in contrast to previous reports. Obesity was associated with core binding factor AML. In study III, we found that time to neutrophil recovery after the first induction course was associated with time to neutrophil recovery after the remaining courses. Furthermore, longer time to neutrophil recovery after the first induction course was associated with increased risk of microbiologically documented infection and increased risk of relapse. In study IV, we found that use of granulocyte colony-stimulating factor (G-CSF) as supportive care was frequent in the cohort, but decreased with time. Use of G-CSF was associated with an increased risk of relapse. Severe acute toxicities, especially infections, are a large problem in the treatment of pediatric AML and measures for prevention are limited. The studies in this thesis have brought further insight into severe toxicities occurring during treatment for pediatric AML, which will be important knowledge in the attempt to minimize the treatment burden in the future.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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 source (direct Gemma or distilled Codex), 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".