AML with adverse-risk biology per ELN 2022: TP53 mutation, complex / monosomal karyotype,...

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

ID	`RF-AML-HIGH-RISK-BIOLOGY`
Type	Red flag
Status	reviewed 2026-04-25 \| pending_clinical_signoff
Diseases	`DIS-AML`
Sources	`SRC-ELN-AML-2022` `SRC-NCCN-AML-2025`

Red Flag Origin

Definition	AML with adverse-risk biology per ELN 2022: TP53 mutation, complex / monosomal karyotype, RUNX1 / ASXL1 mutation, KMT2A rearrangement (other than t(9;11)), inv(3) / t(3;3), -5/del(5q), -7, FLT3-ITD without NPM1, or therapy-related
Clinical direction	intensify
Category	high-risk-biology
Shifts algorithm	ALGO-AML-1L

Trigger Logic

{
  "any_of": [
    {
      "finding": "tp53_mutation",
      "value": true
    },
    {
      "finding": "complex_karyotype",
      "value": true
    },
    {
      "finding": "monosomal_karyotype",
      "value": true
    },
    {
      "finding": "monosomy_7",
      "value": true
    },
    {
      "finding": "del_5q",
      "value": true
    },
    {
      "finding": "inv_3_or_t_3_3",
      "value": true
    },
    {
      "finding": "kmt2a_rearrangement_non_t911",
      "value": true
    },
    {
      "finding": "runx1_mutation",
      "value": true
    },
    {
      "finding": "asxl1_mutation",
      "value": true
    },
    {
      "finding": "flt3_itd_without_npm1",
      "value": true
    },
    {
      "finding": "therapy_related_aml",
      "value": true
    },
    {
      "finding": "aml_eln_risk",
      "value": "adverse"
    }
  ],
  "type": "biomarker"
}

Notes

ELN-2022 adverse-risk patients are alloHCT candidates upfront if fit. Adds urgency to donor search and shifts the post-induction pathway (skip consolidation HiDAC if rapidly bridging to allo). FLT3-ITD with high allelic ratio + NPM1-wt is now classified adverse (down-graded from intermediate in ELN-2017). STUB — requires clinical co-lead signoff.

Used By

Algorithms

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

Indications

IND-AML-1L-7-3-GO-CBF - IND-AML-1L-7-3-GO-CBF
IND-AML-1L-CPX351-SECONDARY - IND-AML-1L-CPX351-SECONDARY
IND-AML-PEDIATRIC-AAML1031 - IND-AML-PEDIATRIC-AAML1031

Red flag

RF-AML-SECONDARY-AML-MRC-CPX351-ELIGIBLE - AML eligible for CPX-351 (Vyxeos) liposomal cytarabine+daunorubicin per the FDA-approved...