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Finding
Finding
decline
Pediatric APL patients with FLT3 mutations who received ATRA-based induction therapy had a dramatically higher induction death rate (30%, 7/23) compared to FLT3 wild-type patients (3%, 1/35), with deaths primarily due to hemorrhagic or ischemic events in the first 5 days of treatment.
| Effect size | 30% vs 3% |
| Comparator | FLT3 wild-type (FLT3/WT) pediatric APL patients receiving ATRA-based induction therapy |
| Effect summary | decline; 30% vs 3% |
| Adverse events | induction death 30% (7/23) in FLT3/Mut vs 3% (1/35) in FLT3/WT, primarily due to hemorrhagic or ischemic events in the first 5 days |
| Effect modifiers | [{"modifier": "Diagnostic WBC count (>10,000 cells/uL)", "interaction_p": "p=0.052", "direction": "amplifies", "stratum_details": "High WBC + FLT3/Mut: 47% induction death (7/15); High WBC + FLT3/WT: 0% (0/8); Low WBC: 1 death in FLT3/WT patient", "plain_language": "FLT3 mutations were even more dangerous in children with high white blood cell counts -- nearly half died during initial treatment, while none of the FLT3-normal children with high WBC died.", "annotation_notes": "p=0.052 is borderline. Multivariate Cox model found FLT3/Mut (p=0.043) and high WBC (p=0.041) each independently prognostic for OS."}, {"modifier": "ITD allelic ratio (AR >= 0.4 vs < 0.4)", "interaction_p": "p=1.0", "direction": "null", "stratum_details": "High-AR: 3/4 (75%) induction deaths had high AR vs 6/9 (67%) survivors had high AR", "plain_language": "The amount of the FLT3 mutation (allelic ratio) did not predict which children with the mutation would die during induction.", "annotation_notes": "Only 13 patients with FLT3/ITD, very small sample. In non-APL AML, high AR predicts worse outcome, but this was not seen in APL."}] |
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Source
PMC3368997
FLT3 Mutation Status is a Predictor of Early Death in Pediatric Acute Promyelocytic Leukemia: A Report From The Children's Oncology Group