Duration Of Neutropenia Is Associated With Reduced Relapse Risk In Children With De Novo Acute Myeloid Leukemia: A Report From The Children’s Oncology Group
Bibliographic record
Abstract
Abstract Background Children receiving treatment for de novo acute myeloid leukemia (AML) commonly experience infections and prolonged duration of neutropenia. There is great variability in these outcomes and pharmacogenomics may provide one mechanism to explain this variability. We hypothesized that relapse outcomes may be inversely related to the degree of toxicity. Objectives To describe the relationship between the number of sterile site infections and duration of neutropenia during the first four cycles of chemotherapy and the risk of recurrence and overall survival. Methods AAML0531 was a Children's Oncology Group (COG) randomized phase 3 clinical trial that included 1022 children with de novo AML enrolled between August 2006 and June 2010. Inclusion criteria were age ≥ 1 month to ≤ 30 years. For this specific analysis, we focused on non-Down syndrome patients who completed at least 4 cycles of chemotherapy on protocol therapy without recurrence on therapy and who did not receive HSCT in first remission. Because high-risk patients were allocated to best allogeneic donor HSCT, we focused on favorable and intermediate risk cytogenetic groups. The treatment protocol consisted of 5 cycles of intensive chemotherapy; patients were randomized to receive or not receive gemtuzumab ozogamicin (GMTZ) during Induction I and Intensification II. The cumulative time to neutrophil recovery between start of Induction II and completion of cycle 4 (Intensification II) was examined; Induction I was not included since many centers did not wait for neutrophil recovery before starting Induction II. Relapsed risk and survival analyses were conducted from the end of Intensification II. Potential confounders explored for this analysis were gender, age, race, weight group, cytogenetic risk group and allocation to GMTZ. Results There were 569 patients included; 279 (49.0%) were male and 210 (36.9%) had favorable risk cytogenetics. There were 1116 sterile site infections; 735 (65.9%) were Gram-positive bacteria. The median cumulative time with neutropenia was 96 (range 46 – 204) days. The Table illustrates that infections did not significantly influence the risk of relapse or overall survival. However, increased duration of neutropenia was associated with a lower risk of relapse both in univariate and multiple regression models after adjustment for African-American race, favorable risk cytogenetics and GMTZ allocation. Conclusions Longer duration of neutropenia is associated with a reduced risk of relapse for children with favorable and intermediate cytogenetic risk AML. Toxicity may be mediated through pharmacogenomics which suggests that individualized chemotherapy dosing may be an effective strategy. Disclosure: No relevant conflicts of interest to declare.
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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 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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".