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

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

ID	`RF-CLL-TP53-DELETION-ACTIONABLE`
Type	Red flag
Status	reviewed 2026-04-27 \| pending_clinical_signoff
Diseases	`DIS-CLL`
Sources	`SRC-CLL14-FISCHER-2019` `SRC-ESMO-CLL-2024` `SRC-NCCN-BCELL-2025`

Red Flag Origin

Definition	CLL with del(17p) by FISH AND/OR TP53 mutation by NGS — ~5-10% at diagnosis, rising to ~30-40% in R/R disease. Defines a chemoimmuno- refractory subset (FCR/BR contraindicated; chemo OS <2 years). 1L selection narrows to two targeted-only routes: continuous BTKi (acalabrutinib, zanubrutinib, ibrutinib) OR fixed-duration venetoclax + obinutuzumab (CLL14, Fischer NEJM 2019; del(17p)/TP53-mut subgroup mPFS >5 years). NCCN/ESMO 2024 prefer fixed-duration ven + obinutuzumab over continuous BTKi for patient-preference and cardiac/bleeding-risk profiles, while continuous BTKi preferred for high disease bulk or patients unable to tolerate TLS-prophylaxis ramp.
Clinical direction	intensify
Category	high-risk-biology
Shifts algorithm	ALGO-CLL-1L

Trigger Logic

{
  "any_of": [
    {
      "finding": "del_17p",
      "value": true
    },
    {
      "finding": "tp53_mutation",
      "value": true
    },
    {
      "finding": "tp53_status",
      "value": "mutated"
    },
    {
      "finding": "BIO-TP53-MUTATION",
      "value": "positive"
    },
    {
      "finding": "tp53_disruption",
      "value": true
    }
  ],
  "type": "biomarker"
}

Notes

Narrower than RF-CLL-HIGH-RISK (which fires on TP53 OR IGHV-unmutated OR complex karyotype) — this flag fires only on TP53-axis disruption, the strongest single negative-prognostic factor and the one with most direct treatment routing. Both fire in parallel for TP53-disrupted cases; resolution: this flag has higher priority (50 vs default 100) and routes to ven+obinutuzumab/BTKi specifically. del(17p) FISH cutoff: most centers use ≥7-10% nuclei positive; TP53 mutation by NGS at VAF ≥5-10% (subclonal TP53 also predicts poor outcome and warrants targeted therapy). Repeat TP53 testing at every relapse (clonal evolution adds del/mut in ~30% late-line). RF-CLL-HIGH-RISK still fires for IGHV-unmutated and complex- karyotype routing.

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

Red Flag Origin

Trigger Logic

Notes

Used By

Algorithms

Indications