MYC + BCL2 (and/or BCL6) rearrangement (double-/triple-hit) confirmed by FISH — DA-EPOCH-...

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

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

Red Flag Origin

Definition	MYC + BCL2 (and/or BCL6) rearrangement (double-/triple-hit) confirmed by FISH — DA-EPOCH-R + IT methotrexate prophylaxis preferred over R-CHOP per multiple retrospective and small prospective series.
Clinical direction	intensify
Category	high-risk-biology
Shifts algorithm	ALGO-HGBL-DH-1L

Trigger Logic

{
  "any_of": [
    {
      "all_of": [
        {
          "finding": "myc_rearrangement",
          "value": true
        },
        {
          "finding": "bcl2_rearrangement",
          "value": true
        }
      ]
    },
    {
      "all_of": [
        {
          "finding": "myc_rearrangement",
          "value": true
        },
        {
          "finding": "bcl6_rearrangement",
          "value": true
        }
      ]
    },
    {
      "finding": "double_hit_lymphoma",
      "value": true
    },
    {
      "finding": "triple_hit_lymphoma",
      "value": true
    }
  ],
  "type": "biomarker"
}

Notes

WHO 2022/ICC define HGBL-DH/-TH as distinct entity. NCCN explicitly endorses DA-EPOCH-R for HGBL-DH; CNS prophylaxis (IT MTX × 4-8 doses) standard regardless of CNS-IPI in this subtype.

Used By

Algorithms

ALGO-HGBL-DH-1L - ALGO-HGBL-DH-1L
ALGO-HGBL-DH-2L - ALGO-HGBL-DH-2L