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TP53-mutierte AML — ELN-2022-Klassifikator für das Risiko-Risiko-Verhältnis und WHO-Entität der 5. Auflage. ~10-15%...

Deterministische Ansicht der Quelle YAML Entität. Klinische Autorität bleibt mit den zitierten Quell-IDs und Rezensenten Sign-off Zustand.

IDRF-AML-TP53-ADVERSE
ArtWarnhinweis
Statusreviewed 2026-04-30 | pending_clinical_signoff
ErkrankungenDIS-AML
QuellenSRC-ELN-AML-2022 SRC-IPSS-M-BERNARD-2022 SRC-NCCN-AML-2025

Ursprung der Roten Flagge

BegriffsbestimmungTP53-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.
Klinische RichtungIntensivierung
Kategoriehigh-risk-biology
Schaltet AlgorithmusALGO-AML-1L, ALGO-AML-2L

Logik auslösen

{
  "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"
}

Anmerkungen

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.

Verwendet von

Biomarker