BRAF V600E wild-type variant HCL (HCL-v) OR IGHV4-34 expression — purine analogs less eff...

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

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

Red Flag Origin

Definition	BRAF V600E wild-type variant HCL (HCL-v) OR IGHV4-34 expression — purine analogs less effective; consider rituximab combination upfront or vemurafenib (for BRAF mutant) in 2L.
Clinical direction	intensify
Category	high-risk-biology

Trigger Logic

{
  "any_of": [
    {
      "finding": "hcl_variant_v",
      "value": true
    },
    {
      "finding": "ighv4_34_positive",
      "value": true
    },
    {
      "finding": "braf_v600e",
      "value": "negative"
    }
  ],
  "type": "biomarker"
}

Notes

HCL-v and IGHV4-34 are predictors of inferior response to single-agent purine analog. Adding rituximab (HCL14 trial: cladribine + rituximab) raises CR rate notably. Indication-level decision, not a 1L Algorithm switch.

Used By

No reverse references found in the YAML corpus.