TP53-mutated AML — ELN-2022 adverse-risk classifier and WHO 5th- edition entity. ~10-15%...

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

ID	`RF-AML-TP53-ADVERSE`
Type	Red flag
Status	reviewed 2026-04-30 \| pending_clinical_signoff
Diseases	`DIS-AML`
Sources	`SRC-ELN-AML-2022` `SRC-IPSS-M-BERNARD-2022` `SRC-NCCN-AML-2025`

Red Flag Origin

Definition	TP53-mutated AML — ELN-2022 adverse-risk classifier and WHO 5th- edition entity. ~10-15% of de-novo AML; enriched (~30-40%) in therapy-related and AML-MRC. Median OS 5-9 months on standard chemo or HMA-based therapy; alloHCT carries higher relapse risk vs TP53-WT AML but remains the only potentially curative pathway. Multi-hit (biallelic) predicts even worse outcome than mono-hit. Routes to: (1) alloHCT consideration when fit, (2) ven+aza backbone for unfit, (3) clinical-trial referral preferentially.
Clinical direction	intensify
Category	high-risk-biology
Shifts algorithm	ALGO-AML-1L, ALGO-AML-2L

Trigger Logic

{
  "any_of": [
    {
      "finding": "aml_tp53_adverse",
      "value": true
    },
    {
      "all_of": [
        {
          "finding": "disease",
          "value": "AML"
        },
        {
          "finding": "tp53_mutation",
          "value": true
        }
      ]
    },
    {
      "all_of": [
        {
          "finding": "disease",
          "value": "AML"
        },
        {
          "finding": "tp53_biallelic",
          "value": true
        }
      ]
    },
    {
      "all_of": [
        {
          "finding": "disease",
          "value": "AML"
        },
        {
          "finding": "del_17p",
          "value": true
        }
      ]
    },
    {
      "all_of": [
        {
          "finding": "disease",
          "value": "AML"
        },
        {
          "comparator": ">=",
          "finding": "tp53_vaf_pct",
          "threshold": 10
        }
      ]
    }
  ],
  "type": "biomarker"
}

Notes

Detection: NGS myeloid panel at diagnosis (mandatory per ELN-2022) + FISH for del(17p13.1). VAF % critical — ≥10% threshold often used for adverse classification (lower-VAF subclonal TP53 may not drive prognosis). Multi-hit definition: biallelic TP53 by either two mutations, mutation + del(17p), or LOH on SNP array. Active research questions: ven+aza (CR ~40% but PFS short ~5 mo), magrolimab+aza (failed phase-3 ENHANCE), eprenetapopt+aza (mixed phase 2/3). Distinct from RF-MDS-TP53-MUTATION (MDS-specific) — AML-scoped routing is more aggressive (alloHCT priority). Algorithm wiring deferred — RF surfaces as adverse-risk annotation; ven+aza backbone + alloHCT bridge for fit per existing ALGO-AML-1L step routing. STUB — requires clinical co-lead signoff.

Used By

Biomarker

BIO-AML-TP53-ADVERSE - TP53-mutated AML (adverse risk)