瀰漫性大 B 細胞淋巴瘤

Buzzwords → Dx

Diagnostic Criteria

• Excisional biopsy is preferred (FNA insufficient) — needed for architecture + IHC + FISH.
• WHO 5e / ICC 2022: "DLBCL, NOS" excludes specific entities (PMBL, primary CNS, leg-type, EBV+, T-cell/histiocyte-rich, etc.).
• Cell-of-origin classification (Hans IHC vs GEP) influences research stratification but does not change first-line treatment outside trials.
• HGBL with MYC + BCL2 ± BCL6 rearrangements (formerly "double-/triple-hit") is its own WHO 5e entity and changes treatment.
• Staging: Lugano (Ann Arbor + bulk + B-symptoms). PET-CT for staging and end-of-treatment response (Deauville score).

Workup

• PET-CT (staging + Deauville at end of treatment).
• Excisional or core biopsy with H&E, IHC (CD20, CD10, BCL6, IRF4/MUM1, MYC, BCL2, Ki-67, CD30, EBER-ISH).
• FISH for MYC, BCL2, BCL6 mandatory (rule out HGBL).
• Bone marrow biopsy if PET equivocal or cytopenias (PET-positive marrow can substitute).
• CSF analysis if CNS-IPI 4–6 or kidney/adrenal/testicular/breast involvement.
• HBV/HCV/HIV serology + echo/MUGA before anthracycline.
• β-hCG in females of reproductive age.

Treatment Algorithm

flowchart TD
  A[Newly diagnosed DLBCL] --> B{HGBL FISH<br>MYC + BCL2 ± BCL6?}
  B -- yes --> C[DA-EPOCH-R<br>± CNS prophylaxis]
  B -- no --> D{Primary mediastinal?}
  D -- yes --> E[DA-EPOCH-R × 6<br>or R-CHOP ± RT]
  D -- no --> F{Primary CNS?}
  F -- yes --> G[HD-MTX backbone<br>± ASCT or WBRT consolidation<br>NO STEROIDS pre-biopsy]
  F -- no --> H{IPI / NCCN-IPI risk}
  H -- low IPI 0-1<br>or early-stage --> I[R-CHOP × 4-6<br>± involved-site RT]
  H -- IPI ≥2<br>advanced --> J[Pola-R-CHP × 6<br>POLARIX category 1]
  I --> K{CNS-IPI 4-6 OR<br>kidney/adrenal/testis/breast?}
  J --> K
  C --> K
  K -- yes --> L[CNS prophylaxis<br>HD-MTX IV preferred over IT]
  K -- no --> M[End-of-treatment PET<br>Deauville 1-3 = CR]
  L --> M
  M --> N{Relapse / refractory?}
  N -- ≤12 mo or primary refractory --> O[2L = CAR-T<br>axi-cel ZUMA-7 or liso-cel TRANSFORM]
  N -- >12 mo, transplant-eligible --> P[Platinum salvage R-ICE/R-DHAP → ASCT]
  N -- post-CAR-T progression --> Q[Bispecifics<br>epcoritamab / glofitamab]

Pearls / Pitfalls

• Pola-R-CHP is only for advanced-stage IPI ≥2 (or smIPI >1 in stage I-II). Not studied in and not recommended for IPI 0–1. Picking Pola-R-CHP for low-risk DLBCL is the wrong answer.⁴²
• Double-expressor ≠ Double-hit. DEL = IHC protein co-expression (MYC ≥40 % + BCL2 ≥50 %); double-hit/HGBL = FISH-confirmed rearrangements. DEL is treated as standard DLBCL with R-CHOP/Pola-R-CHP, NOT escalated to DA-EPOCH-R.⁵
• CNS-IPI ≠ IPI. CNS-IPI adds kidney/adrenal involvement as a sixth risk factor. HD-MTX (IV ≥3–3.5 g/m²) is preferred over IT chemo for parenchymal CNS prophylaxis — most rituximab-era relapses are parenchymal (~70–80 %), which IT poorly penetrates. Recent retrospective data even question whether prophylaxis reduces CNS relapse at all — this is an evolving area.⁶⁷
• MYC + BCL6 (no BCL2) is NOT high-grade. Only MYC + BCL2 (± BCL6) by FISH defines HGBL/double-hit. Isolated MYC + BCL6 rearrangement is managed as standard DLBCL.⁵
• Avoid steroids before primary CNS lymphoma biopsy — they cause rapid lymphocyte lysis and can render biopsy non-diagnostic for weeks.
• CAR-T 2L beats ASCT for early relapse. ZUMA-7 (axi-cel) and TRANSFORM (liso-cel) both showed superior EFS vs salvage chemo + ASCT in primary-refractory/early-relapse DLBCL. Bridging therapy (Pola-R-bendamustine, R-ICE, GDP, GEMOX) is essential to control disease pre-leukapheresis. Hold bendamustine until AFTER leukapheresis to avoid T-cell depletion.³⁸
• CAR-T toxicities: see CART — CRS (tocilizumab + steroids), ICANS (steroids; tocilizumab does NOT cross BBB).

Cross-references

• Staging — IPI, R-IPI, NCCN-IPI, CNS-IPI, Lugano
• Drug Regimens — R-CHOP, Pola-R-CHP, DA-EPOCH-R, R-ICE
• Cytogenetics Atlas — MYC, BCL2, BCL6
• CAR-T (axi-cel, liso-cel, tisa-cel)
• Primary CNS Lymphoma
• Tumor Lysis Syndrome (high pre-Tx LDH)

相關題目

• Q-002 — DLBCL — second-line therapy for primary-refractory disease
• Q-038 — DLBCL — CNS prophylaxis decision
• Q-039 — DLBCL — double-hit vs double-expressor
• Q-051 — Burkitt vs HGBL — distinguishing by FISH and IHC
• Q-146 — Auto-HCT — when to use vs CAR-T for DLBCL
• Q-186 — Cord compression — radiosensitive lymphoma
• Q-189 — SVC syndrome from primary mediastinal B-cell lymphoma (PMBL)
• Q-206 — HBV reactivation prophylaxis

Sources

Drafted from OpenEvidence query 2026-05-07; cross-checked against POLARIX 5-yr update (JCO 2025) and ZUMA-7/TRANSFORM 2L data.