NPM1 mutation (most commonly type-A: c.860_863dupTCTG / p.W288fs) in AML — ~30% of adult...

Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.

ID	`RF-AML-NPM1-MUT-FAVORABLE`
Type	Red flag
Status	reviewed 2026-04-27 \| pending_clinical_signoff
Diseases	`DIS-AML`
Sources	`SRC-ELN-AML-2022` `SRC-ESMO-AML-2020` `SRC-NCCN-AML-2025`

Red Flag Origin

Definition	NPM1 mutation (most commonly type-A: c.860_863dupTCTG / p.W288fs) in AML — ~30% of adult AML; ~50% of cytogenetically normal AML. ELN-2022 favorable risk when NPM1-mutated WITHOUT FLT3-ITD; standard 7+3 induction first-line (no upfront alloHCT in CR1; consolidation HiDAC × 3-4 cycles is curative-intent). MRD qPCR (NPM1-mut transcript) for monitoring.
Clinical direction	de-escalate
Category	high-risk-biology
Shifts algorithm	ALGO-AML-1L

Trigger Logic

{
  "all_of": [
    {
      "any_of": [
        {
          "finding": "npm1_mutation",
          "value": true
        },
        {
          "finding": "npm1_status",
          "value": "mutated"
        },
        {
          "finding": "npm1_type_a",
          "value": true
        }
      ]
    },
    {
      "any_of": [
        {
          "finding": "flt3_itd",
          "value": false
        },
        {
          "finding": "flt3_itd_status",
          "value": "negative"
        }
      ]
    }
  ],
  "type": "composite_score"
}

Notes

De-escalate direction reflects "do NOT intensify to upfront alloHCT" — favorable-risk patients receive standard chemo with curative intent; alloHCT reserved for MRD-positive after consolidation OR early relapse. NPM1-mut + FLT3-ITD high-allelic-ratio downgrades to intermediate (and now adverse per ELN-2022 if NPM1-WT). MRD-NPM1 qPCR threshold ≥2-log reduction = molecular response; MRD-positive after consolidation → consider alloHCT. Menin inhibitors (revumenib, ziftomenib) — investigational R/R NPM1-mut. RF coexists with RF-AML-FLT3-ACTIONABLE (different axes — NPM1+FLT3-ITD case fires both).

Used By

Algorithms

ALGO-AML-1L - ALGO-AML-1L