MDS with TP53 mutation (mono- or biallelic) — distinct WHO 5th-ed entity with poor outcom...

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

ID	`RF-MDS-TP53-MUTATION`
Type	Red flag
Status	reviewed 2026-04-25 \| pending_clinical_signoff
Diseases	`DIS-MDS-HR` `DIS-MDS-LR`
Sources	`SRC-ESMO-MDS-2021` `SRC-IPSS-M-BERNARD-2022` `SRC-NCCN-AML-2025`

Red Flag Origin

Definition	MDS with TP53 mutation (mono- or biallelic) — distinct WHO 5th-ed entity with poor outcomes on HMA monotherapy and reduced alloHCT benefit; consideration of intensified / experimental therapy or palliative intent
Clinical direction	intensify
Category	high-risk-biology
Shifts algorithm	ALGO-MDS-HR-1L

Trigger Logic

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

Notes

TP53-mutated MDS is its own WHO 5th-edition entity with median OS ~6-9 months on standard HMA. AlloHCT carries higher relapse risk vs TP53-wt. Active research questions: ven+aza vs aza alone, magrolimab + aza (failed phase-3 ENHANCE), eprenetapopt + aza (mixed results). NOT clear best regimen — flagged as intensify but the algorithm should also surface palliative-intent option. STUB — requires clinical co-lead signoff.

Used By

Algorithms

ALGO-MDS-HR-1L - ALGO-MDS-HR-1L
ALGO-MDS-HR-2L - ALGO-MDS-HR-2L

Biomarker

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

Indications

IND-MDS-HR-1L-AZA - IND-MDS-HR-1L-AZA
IND-MDS-HR-ALLOHCT - IND-MDS-HR-ALLOHCT
IND-MDS-LR-LENALIDOMIDE-DEL5Q - IND-MDS-LR-LENALIDOMIDE-DEL5Q

Red flag

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