Diffuse large B-cell lymphoma (DLBCL)

Overview

•Most common non-Hodgkin lymphoma subtype - 30-35% of all NHL

•Peak incidence sixth and seventh decades; slightly more common in men

•Aggressive but potentially curable - 60-70% achieve long-term remission with R-CHOP

•Richter transformation - CLL transforming into DLBCL; suspect if known CLL patient develops sudden dramatic lymph node enlargement + B-symptoms

Risk factors

Increasing age - sixth/seventh decade

HIV / post-transplant immunosuppression

Autoimmune conditions (Sjögren, SLE, RA)

EBV infection (especially immunosuppressed)

H. pylori - gastric B-cell lymphomas

Richter transformation from CLL

Family history of lymphoma

Presentation

•Rapidly enlarging, firm, non-tender lymphadenopathy (cervical, axillary, or inguinal) - weeks to months

•B-symptoms (present in ~30-40%) - fever >38°C, drenching night sweats, weight loss >10% over 6 months

•Splenomegaly/hepatomegaly - lymphoma infiltration

•Mediastinal mass - may cause SVC obstruction (facial plethora, arm swelling, dyspnoea)

•GI disease - abdominal pain, bowel obstruction/perforation

•CNS involvement - headache, cranial nerve palsies, confusion

•Fatigue and anaemia - bone marrow infiltration

Investigations

🏆 Gold standard

•Excision biopsy of intact lymph node - full architectural assessment, subtyping by immunohistochemistry; FNA alone is NOT sufficient

•First-line bloods: FBC, LDH (elevated = high cell turnover; IPI component), uric acid, U&E, LFTs, calcium, HIV, hepatitis B and C serology

•Staging: PET-CT - standard of care; superior to CT alone for staging and treatment response assessment

•CT chest/abdomen/pelvis with contrast - staging if PET-CT unavailable

•Bone marrow trephine biopsy - if bone marrow involvement suspected or PET-CT equivocal

•Echocardiogram - mandatory before doxorubicin (cardiotoxic); assesses baseline LVEF

⚠️

HIV, hepatitis B and C serology are mandatory before rituximab - HBV reactivation is a serious risk. Patients with past HBV exposure require entecavir prophylaxis.

Management

🥇 First-line

•R-CHOP x6 cycles (every 21 days) - standard of care for most DLBCL

•Rituximab - anti-CD20 monoclonal antibody

•Cyclophosphamide - alkylating agent

•Doxorubicin - anthracycline, inhibits topoisomerase II

•Vincristine - vinca alkaloid, arrests mitosis

•Prednisolone - corticosteroid

•Stage I-II limited disease: 4 cycles R-CHOP + involved-field radiotherapy (IFRT)

•Second-line (relapsed/refractory): salvage chemotherapy (R-ICE or R-DHAP) → autologous stem cell transplant (ASCT) in eligible patients

🥉 Third-line

•CAR-T cell therapy (axicabtagene ciloleucel, tisagenlecleucel) - NICE-approved after ≥2 prior lines

•TLS prophylaxis: allopurinol or rasburicase in high-tumour-burden disease

🎯

Doxorubicin is contraindicated in significantly impaired LV function. In these patients, discuss anthracycline-sparing regimens at MDT (e.g. R-CEOP substituting etoposide for doxorubicin) - a classic exam scenario.

Complications

•Tumour lysis syndrome (TLS) - ↑K⁺, ↑uric acid, ↑phosphate, ↓calcium → AKI, arrhythmias, seizures; highest risk in bulky disease

•Neutropenic sepsis - most common life-threatening R-CHOP toxicity; fever during chemotherapy = medical emergency

•Cardiotoxicity - cumulative doxorubicin → dilated cardiomyopathy; monitor with serial echocardiography

•CNS relapse - ~5% overall; higher risk with CNS-IPI 4-6, testicular DLBCL, double-hit lymphoma

•Peripheral neuropathy - vincristine-related; often dose-limiting

•Secondary malignancies - MDS/AML from alkylating agents (long-term risk)

Prognosis

•~60-70% achieve long-term remission with R-CHOP; prognosis strongly influenced by IPI score, cell-of-origin subtype, and double-hit biology

•GCB subtype - better prognosis than ABC subtype

•Double-hit/triple-hit lymphoma (MYC + BCL-2/BCL-6 rearrangements) - significantly worse prognosis; requires intensified regimens beyond R-CHOP

•Relapsed disease: ~40-50% cured with ASCT if chemosensitive; CAR-T has transformed outcomes in multiply relapsed/refractory disease

Staging and prognostic scoring

•Ann Arbor staging - I (single node region) to IV (disseminated/extranodal); suffix A (no B-symptoms) or B (B-symptoms present)

•International Prognostic Index (IPI) - 5 factors, 1 point each:

•Age >60 years

•Ann Arbor stage III or IV

•Elevated serum LDH

•ECOG performance status ≥2

•More than one extranodal site

•Score 0-1 = low risk (~73% 5-year OS); 4-5 = high risk (~26% 5-year OS)

•CNS-IPI - adds renal/adrenal involvement; score 4-6 = high CNS relapse risk; consider CNS prophylaxis with high-dose systemic methotrexate