CLL with high-risk genetics: TP53 mutation OR del(17p) OR IGHV-unmutated OR complex karyo...

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

ID	`RF-CLL-HIGH-RISK`
Type	Red flag
Status	reviewed 2026-04-25 \| pending_clinical_signoff
Diseases	`DIS-CLL`
Sources	`SRC-ESMO-CLL-2024` `SRC-NCCN-BCELL-2025`

Red Flag Origin

Definition	CLL with high-risk genetics: TP53 mutation OR del(17p) OR IGHV-unmutated OR complex karyotype (≥3 abnormalities)
Clinical direction	intensify
Category	high-risk-biology
Shifts algorithm	ALGO-CLL-1L

Trigger Logic

{
  "any_of": [
    {
      "finding": "BIO-CLL-HIGH-RISK-GENETICS",
      "value": "positive"
    },
    {
      "finding": "BIO-TP53-MUTATION",
      "value": "positive"
    },
    {
      "finding": "BIO-IGHV-MUTATIONAL-STATUS",
      "value": "unmutated"
    },
    {
      "finding": "tp53_mutation",
      "value": true
    },
    {
      "finding": "del_17p",
      "value": true
    },
    {
      "finding": "ighv_unmutated",
      "value": true
    },
    {
      "finding": "complex_karyotype",
      "value": true
    }
  ],
  "type": "biomarker"
}

Notes

Triggers preference for fixed-duration venetoclax+obinutuzumab (CLL14) over BTKi continuous in some patient profiles, AND absolutely contraindicates chemoimmunotherapy (FCR/BR). High-risk CLL must NEVER receive chemoimmuno 1L — survival impact substantial.

Used By

Algorithms

ALGO-CLL-1L - ALGO-CLL-1L

Biomarker

BIO-IGHV-MUTATIONAL-STATUS - IGHV (immunoglobulin heavy-chain variable region) mutational status
BIO-TP53-MUTATION - TP53 mutation / del(17p)

Indications

IND-CLL-1L-BTKI - IND-CLL-1L-BTKI
IND-CLL-1L-VENO - IND-CLL-1L-VENO

Questionnaires

QUEST-CLL-1L - Chronic Lymphocytic Leukemia / SLL — first line

Red flag

RF-CLL-TP53-DELETION-ACTIONABLE - CLL with del(17p) by FISH AND/OR TP53 mutation by NGS — ~5-10% at diagnosis, rising to ~3...