What is large B‑cell lymphoma?

What is Large B-Cell Lymphoma?

Large B-cell lymphoma, specifically diffuse large B-cell lymphoma (DLBCL), is an aggressive malignancy of mature B lymphocytes that represents the most common subtype of non-Hodgkin lymphoma, accounting for 30-58% of all cases. 1

Epidemiology and Incidence

• The crude incidence in Europe is 3-4 per 100,000 people per year 1
• Incidence increases dramatically with age, from 0.3/100,000/year in patients aged 35-39 years to 26.6/100,000/year in those aged 80-84 years 1
• Risk factors include family history of lymphoma, autoimmune disease, HIV infection, hepatitis C seropositivity, high body mass in young adulthood, and certain occupational exposures 1

Clinical Presentation

• Patients typically present with a rapidly growing tumor mass that can occur in single or multiple sites, either nodal or extranodal 2
• The disease is clinically heterogeneous, with approximately 40% of patients responding well to therapy with prolonged survival, while 60% have variable outcomes 2, 3

Molecular and Pathologic Classification

DLBCL is molecularly heterogeneous, with gene expression profiling identifying two major subtypes based on cell-of-origin: 3

• Germinal center B-cell-like (GCB) subtype: Expresses genes characteristic of germinal center B cells and has significantly better overall survival 3
• Activated B-cell-like (ABC) subtype: Expresses genes induced during peripheral blood B-cell activation and has worse prognosis 3
• Approximately 10-15% of cases remain unclassifiable 2

The distinction between these subtypes does not currently influence initial treatment choices, though this remains an active area of research 1

Diagnostic Requirements

Diagnosis must be established through surgical excision biopsy or adequate tissue biopsy processed by an experienced hematopathology laboratory: 1

• Core biopsies are acceptable only in rare patients requiring emergency treatment 1
• Minimal mandatory immunohistochemistry includes CD45, CD20, and CD3 to confirm B-cell lineage 1
• The histological report must follow current WHO classification 1
• Fresh frozen material collection for molecular characterization is recommended, though gene expression profiling remains investigational 1

Staging and Prognosis

Risk stratification uses the International Prognostic Index (IPI) and age-adjusted IPI (aa-IPI), which remain the standard prognostic tools: 1

• Required baseline workup includes complete blood count, lactate dehydrogenase (LDH), uric acid, HIV and hepatitis B/C screening 1
• CT scan of chest and abdomen plus bone marrow aspirate and biopsy are mandatory for patients amenable to curative therapy 1
• PET-CT scanning is strongly recommended to delineate disease extent and evaluate treatment response 1
• Staging follows the Ann Arbor system 1

Treatment Overview

Standard first-line therapy for CD20-positive DLBCL consists of 6-8 cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) given every 21 days: 1

• Treatment strategies are stratified by age, aa-IPI score, and feasibility of dose-intensified approaches 1
• In high tumor burden cases, prephase corticosteroid treatment (e.g., prednisone 100 mg orally for several days) is required to prevent tumor lysis syndrome 1
• Dose reductions for hematologic toxicity should be avoided; febrile neutropenia justifies prophylactic growth factor use 1

Relapsed/Refractory Disease

• Over 30% of patients will ultimately relapse 1
• For patients refractory or relapsing within 1 year and fit for therapy, CAR T-cell therapy is now the gold standard in second-line treatment 4
• Histological verification is mandatory for relapses occurring >12 months after initial diagnosis 1

Important Clinical Pitfalls

• CNS prophylaxis should be considered in high-risk patients (>2 IPI adverse parameters), especially those with bone marrow, testis, spine, or skull base involvement 1
• Cardiac function (left ventricular ejection fraction) must be assessed before anthracycline-based therapy 1
• The cumulative anthracycline dose must be tracked to prevent cardiotoxicity 1