Excess Treatment-Related Mortality in Obese Children and Adolescents with Acute Myeloid Leukemia on AAML0531: A Report from the Children's Oncology Group
Bibliographic record
Abstract
Abstract Background: Therapy for children with acute myeloid leukemia (AML) is intensive and treatment-related mortality (TRM) occurs in about 5 to 10% of patients. Previous data illustrated that obese children and adolescents with AML treated according to CCG 2961 were more likely to experience TRM, with HR 2.66 (95% CI 1.38-5.11; P = 0.003), when compared to middleweight patients. Since this trial, the backbone of AML chemotherapy and supportive care have changed and thus, it is unknown whether the impact of obesity persists in contemporary trials. The objective was to determine whether obesity was associated with increased TRM, reduced survival and prolonged compared to middleweight patients with AML. Methods: AAML0531 enrolled patients between August 14, 2006 and June 15, 2010. For this analysis, we included patients 0 to 18 years of age with de novo AML. Chemotherapy consisted of 5 cycles of chemotherapy and patients were randomized to receive or not receive gemtuzumab once during Induction I and Intensification II. Best allogeneic donor hematopoietic stem cell transplantation (HSCT) was recommended for those with > 15% bone marrow blasts after Induction I in those without favorable risk cytogenetics and poor risk cytogenetics irrespective of response following Induction I. Matched family donor HSCT was recommended for those with good response after Induction I with standard risk cytogenetics and an available donor. Obesity was defined using definitions from the Centers for Disease Control and Prevention (CDC). Underweight was defined as a body mass index percentile less than 5th percentile, and obese 95th percentile and greater. Categories were determined using z-scores for the weight-for-height data for those 0 to 2 years of age. All outcomes were censored at the time of HSCT. The primary outcome was TRM, defined as death as first event occurring on therapy or within 30 days of going off therapy. Cumulative incidence of TRM was estimated treating relapse and failure as competing events. Kaplan Meier analysis was conducted for overall survival (OS), event free survival (EFS), and disease free survival (DFS). Cumulative incidence of relapse rate (RR) was estimating treating deaths as competing events. Results: There were 1004 patients included. When comparing middleweight and obese patients, there was no significant difference in gender (P=0.814), white vs non-white race (P=0.116), cytogenetic risk group (all P>0.05) or MRD positivity after Induction 1 (P=0.750). The median age was higher for obese patients (12.0 vs 9.4 years; P=0.007 years) compared with middle weight patients. The proportion of patients who were Hispanic or Latino patients was higher among obese compared with middle weight patients (28% vs 17%; P=.001). Survival outcomes are shown in Table 1. When evaluating median time to neutrophil recovery, obese patients, when compared to middleweight patients, had shorter duration of neutropenia for cycles 1-3 (P<0.05). Conclusions: TRM rates continue to be higher for obese patients treated with contemporary AML protocols. Toxicity is not mediated through prolonged neutropenia. Future work should compare the rate of toxicity among obese versus non-obese patients and evaluate the impact of underweight status. Disclosures 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 | 0.001 |
| 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 | 0.000 |
| 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".