Diffuse Large B-Cell Lymphoma

Diffuse large B-cell lymphoma (DLBCL), a form of non-Hodgkin lymphoma, is the most common blood cancer. Lymphomas occur when cells of the immune system, known as B lymphocytes, grow and multiply uncontrollably. DLBCL occurs mostly in adults and is a fast-growing (aggressive) lymphoma. It can start in the lymph nodes or outside of the lymphatic system in the gastrointestinal tract, testes, thyroid, skin, breast, bone, or brain.

Signs and symptoms

the first sign of DLBCL is a painless rapid swelling in the neck, armpit, abdomen, or groin caused by enlarged lymph nodes. For some people, the swelling may be painful. Other symptoms include night sweats, unexplained fevers, and weight loss.

cause

The causes of diffuse large B-cell lymphoma are not well understood. Usually DLBCL arises from normal B cells, but it can also represent a malignant transformation of other types of lymphoma (particularly marginal zone lymphomas or, in rare cases termed Richter's transformation, chronic lymphocytic leukemia. An underlying immunodeficiency is a significant risk factor for development of the disease. Infections with the Epstein–Barr virus,Kaposi's sarcoma-associated herpesvirus, human immunodeficiency virus (i.e. HIV),and the Helicobacter pylori bacterium are also associated with the development of certain subtypes of diffuse large B-cell lymphoma. However, most cases of this disease are associated with the unexplained step-wise acquisition of increasing numbers of gene mutations and changes in gene expression that occur in, and progressively promote the malignant behavior of, certain B-cell types.

Diagnosis

Diagnosis of DLBCL is made by removing a portion of the tumor through a biopsy, and then examining this tissue using a microscope. Usually a hematopathologist makes this diagnosis. Numerous subtypes of DLBCL have been identified which differ in their clinical presentations, biopsy findings, aggressive characteristics, prognoses, and recommended treatments

Microscopic examinations of involved tissues reveal large neoplastic cells that are typically classified as B-cells based on their expression of B-cell marker proteins (e.g. CD20, CD19, CD22, CD79, PAX5, BOB1, OCT2, an immunoglobulin [usually IgM but occasionally IgG or IgA)] CD30and in ~20-25% of cases PD-L1 or PD-L2 (PD-L1 and PD-L2 are transmembrane proteins that normally function to suppress attack by the immune system). These cells arrange in a diffuse pattern, efface the tissues' architecture, and resemble Centroblast cells (80% of cases), Immunoblast cells (8-10% of cases), or anaplastic cells (9% of cases; anaplastic cells have bizarre nuclei and other features that may mimic the Reed-Sternberg cells of Hodgkin disease or the neoplastic cells of anaplastic large cell lymphoma).

Rarely, these neoplastic cells are characterized as having signet ring or spindle shaped nuclei, prominent cytoplasmic granules, multiple microvillus projections, or, when viewed by electron microscopy

Genetics

Most cases of DLBCL, NOS appear to result at least in part from the step-wise development of gene changes such as mutations, altered expressions, amplifications (i.e. increases in the number of copies of specific genes), and tranlocations from normal sites to other chromosomal sites.

Changes in the following genes occur frequently in, and are suspected of contributing to, this disease's development and/or progression.

BCL2,BCL6,MYC,EZH2,MYD88 ,CREBBP,CD79A,PAX5

Treatment

Treatment may differ depending on the location of the tumor and the subtype of lymphoma. For those who have advanced DCBCL and have not been treated previously, a combination of chemotherapy and the monoclonal antibody rituximab (Rituxan) (R-CHOP) may be tried. Axicabtagene ciloleucel (brand name: Yescarta), a type of gene therapy, has been approved by the United States FDA to treat DCBCL that is not responding to at least two treatment attempts or has returned after being treated before. A stem cell transplant may also be an option if DLBCL returns or relapses.

The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition.

• Tisagenlecleucel-T (Brand name: Kymriah)KYMRIAH is a CD19-directed genetically modified autologous T-cell immunotherapy indicated for the treatment of patients with diffuse large B-cell lymphoma, high-grade B-cell lymphoma, or DLBCL arising from follicular lymphoma who received two or more lines of systemic therapy.

• Rituximab and hyaluronidase human (Brand name: Rituxan Hycela)Treatment of adult patients with previously untreated diffuse large B-cell lymphoma in combination with cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) or other anthracycline-based chemotherapy regimens.
• Axicabtagene ciloleucel (Brand name: Yescarta)Treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high-grade B-cell lymphoma, and DLBCL arising from follicular lymphoma.

NIH genetic and rare disease info

• NIH info on Diffuse Large B-Cell Lymphoma

Diffuse Large B-Cell Lymphoma is a rare disease.

Diffuse Large B-Cell Lymphoma Resources
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