Diffuse large B-cell lymphoma
Overview
DLBCL is the most common aggressive B-cell malignancy (~30-40% of all NHL), median age 65-70 years. Aggressive but potentially curable with immunochemotherapy.
Presentation
•Rapidly enlarging lymphadenopathy - painless, firm; cervical, axillary, inguinal, mediastinal, retroperitoneal
•B symptoms - fever >38°C, drenching night sweats, weight loss >10% over 6 months (present in ~30-40%)
•Extranodal disease (up to 40%) - GI tract, bone marrow, CNS, testes, skin, liver, Waldeyer's ring
•Cytopenias - fatigue, pallor, bleeding if bone marrow infiltrated
•SVC obstruction - mediastinal mass causing facial swelling, arm oedema, distended neck veins
Investigations
•Gold standard diagnosis: excision biopsy of accessible lymph node - provides tissue for histology, IHC, flow cytometry, FISH, molecular profiling. Core needle biopsy acceptable if excision not feasible; FNA alone is insufficient
•IHC panel - CD20+, CD19+, CD79a+, CD3-; Ki-67 typically >40% (often >80%); Hans classifier (CD10, BCL-6, MUM1) for GCB vs ABC subtype
•FISH for MYC, BCL-2, BCL-6 - identifies double-hit/triple-hit lymphoma requiring treatment escalation beyond standard R-CHOP
•PET-CT (whole body) - superior to CT for staging; provides baseline for response assessment (Deauville scoring)
•LDH - elevated; key IPI component, reflects tumour burden
•Hepatitis B (HBsAg, anti-HBc), hepatitis C, HIV - mandatory before rituximab; HBV reactivation can be fatal
•Echocardiogram/LVEF - required before anthracycline (doxorubicin); contraindicated in severe cardiac dysfunction
•Lumbar puncture (CSF cytology + flow cytometry) - indicated if CNS-IPI ≥4, neurological symptoms, or high-risk extranodal sites (testes, paranasal sinuses, epidural)
•Bone marrow trephine - if PET-CT cannot exclude BM involvement or unexplained cytopenias
Management
•Pre-treatment: allopurinol + IV hydration to prevent tumour lysis syndrome; hepatitis B prophylaxis (entecavir or tenofovir) for HBsAg+ or anti-HBc+ patients
•First-line (fit patients): R-CHOP-21 (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) x 6 cycles - goal is cure
•G-CSF prophylaxis (filgrastim or pegfilgrastim) - standard with R-CHOP to reduce febrile neutropenia
•Double/triple-hit lymphoma: DA-EPOCH-R preferred over standard R-CHOP
•Frail/elderly: dose-reduced R-miniCHOP or non-anthracycline alternative (R-CEOP with etoposide substituting for doxorubicin)
•Response assessment: interim and end-of-treatment PET-CT using Deauville scoring
•Relapsed/refractory disease: salvage chemotherapy → autologous stem cell transplant (ASCT) if second remission achieved; CAR-T cell therapy for multiply relapsed disease
Complications
•Tumour lysis syndrome - hyperkalaemia, hyperphosphataemia, hypocalcaemia, hyperuricaemia, AKI; prevent with allopurinol/rasburicase and IV hydration
•Febrile neutropenia - most common treatment emergency; nadir 7-14 days post-chemotherapy; treat with broad-spectrum IV antibiotics + G-CSF
•Hepatitis B reactivation - rituximab-related immunosuppression; fatal if missed; screen all patients before treatment
•Cardiotoxicity - doxorubicin causes dose-dependent cardiomyopathy → reduced LVEF → heart failure
•CNS relapse - ~5% overall, up to 15% in high CNS-IPI groups; very poor prognosis
•Secondary malignancy - MDS/AML after alkylating agents; secondary solid tumours after radiotherapy
Prognosis
•R-CHOP achieves long-term remission in ~60-70% of patients overall
•GCB subtype responds better to R-CHOP than ABC subtype
•Double/triple-hit: median OS <2 years with R-CHOP alone
•Relapse after first-line therapy - salvage + ASCT can still be curative; CAR-T offers durable responses in multiply relapsed disease
Prognostic scoring - IPI
International Prognostic Index (IPI) - one point each for five adverse features:
•Age >60 years
•Elevated LDH
•ECOG performance status ≥2
•Ann Arbor stage III or IV
•>1 extranodal site
IPI risk group and 5-year overall survival
| Risk group | IPI score | 5-year OS |
|---|---|---|
| Low risk | 0-1 | ~70-80% |
| Low-intermediate | 2 | ~60-70% |
| High-intermediate | 3 | ~40-50% |
| High risk | 4-5 | ~30-50% |
•CNS-IPI adds renal and adrenal involvement to the five IPI factors; score ≥4 = high CNS relapse risk (~10-15% at 2 years) - consider CNS prophylaxis
Molecular subtypes
GCB vs ABC DLBCL
| Feature | GCB | ABC (non-GCB) |
|---|---|---|
| Cell of origin | Germinal centre B cell | Post-germinal centre B cell |
| Key driver | BCL-2/BCL-6 alterations, t(14;18) | Constitutive NF-κB activation |
| Prognosis with R-CHOP | Better | Worse |