Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma and is an aggressive blood cancer that originates in the lymphatic system and affects B-lymphocytes, which is a type of white blood cell that helps to fight infection. Diffuse large B-cell lymphoma and can occur in one area of the body or throughout the body, and mainly occurs in individuals over the age of 60.  Diffuse large B-cell lymphoma is categorized by the following subtypes: T-cell/histiocyte-rich B-cell lymphoma – This subtype of diffuse large B-cell lymphoma has some scattered large and atypical B cells mixed with many normal T cells and histocytes (immune system cells). Primary diffuse large B-cell lymphoma of the central nervous system – This subtype of diffuse large B-cell lymphoma originates in either the brain or eye and can be a secondary development. Primary cutaneous diffuse large B-cell lymphoma, leg type – This subtype of diffuse large B-cell lymphoma is composed of large transformed B cells that create red or bluish-red tumors and can also involve the arms, trunk, buttocks, legs, or other areas. Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma of the elderly – This subtype of diffuse large B-cell lymphoma mainly occurs in patients over the age of 50 who test positive for the Epstein-Barr virus. Diffuse large B-cell lymphoma not otherwise specified (NOS) – This subtype of diffuse large B-cell lymphoma is for any that does not fall into one of the above classifications and represents 25-30% of diffuse large B-cell lymphoma in western countries. In addition to subtypes, diffuse large B-cell lymphoma is classified into the following stages: Stage I – The diffuse large B-cell lymphoma appears in one lymph node area or a cluster of nearby lymph nodes. Stage II – The diffuse large B-cell lymphoma appears in two lymph node area or has spread (metastasized) to one organ and nearby lymph nodes but is limited to an area of the body above or below the diaphragm.  Stage III – The diffuse large B-cell lymphoma appears in lymph nodes both above and below the diaphragm and may also appear in the spleen. Stage IV – This advanced stage diffuse large B-cell lymphoma appears in several areas of one or more organs and tissues and may also affect the liver, lungs, or bones. Diffuse large B-cell lymphoma is further classified by A or B to denote whether the patient is experiencing any significant symptoms (A), or if the patient has significant symptoms, such as unexplained weight loss, persistent fever, or severe night sweats (B).

There are several alternative names for diffuse large B-cell lymphoma, including Blood cancer, Diffuse large B-cell lymphoma not otherwise specified (NOS), DLBCL, Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma of the elderly, Lymphoma, Non-Hodgkin’s lymphoma (NHL), Primary cutaneous diffuse large B-cell lymphoma, leg type, Primary diffuse large B-cell lymphoma of the central nervous system, and T-cell/histiocyte-rich B-cell lymphoma.

While the exact cause of diffuse large B-cell lymphoma is unknown, researchers believe that this cancer begins when a weakened immune system leads to changes in lymphocytes (a type of white blood cell) that develop abnormalities, and then begin dividing and forming tumors in the lymphatic tissue, usually the lymph nodes. While normal lymphocytes usually eventually die, in diffuse large B-cell lymphoma lymphocytes continue to grow, causing swelling in the lymph nodes, and eventually spreading (metastasizing) to other lymphatic tissues, such as the adenoids, tonsils, lymphatic vessels, thymus, spleen, and bone marrow. Additional factors that increase the risk of developing diffuse large B-cell lymphoma include taking medications that suppress the immune system (immunosuppressive therapy), bacterial or viral infections, especially HIV, Epstein-Barr infection, and Helicobacter pylori, exposure to chemicals, such as pesticides and weed-killers, exposure to radiation, and being male, Caucasian, having had previous radiation and chemotherapy, or being over the age of 60.

The initial symptom of diffuse large B-cell lymphoma is usually swollen lymph nodes in the neck, armpits, or groin (lymphadenopathy) that may grow rapidly. Additional symptoms of diffuse large B-cell lymphoma include persistent fatigue, unexplained weight loss, night sweats, rash, itching, chest pain, coughing, or difficulty breathing (dyspnea), abdominal pain or swelling, bone pain, and fever.

Since diffuse large B-cell lymphoma is aggressive and grows rapidly, immediate treatment is required, which is determined by how far the cancer has spread, and includes chemotherapy, radiation therapy, biologic therapy (CAR T Cell therapy), and bone marrow transplant (stem cell transplant). Chemotherapy – Chemotherapy for diffuse large B-cell lymphoma is usually the primary treatment, for which a four-drug regimen called R-CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone ) is administered in cycles of 3 weeks apart. The number of cycles may be increased depending on the stage of the cancer and/or may be followed by radiation therapy. Chemotherapy may be administered via pill (orally), intravenously (IV), or, in severe cancer, intrathecally (directly into spinal fluid). The drug methotrexate may also be administered during R-CHOP or another chemotherapy drug, etoposide (Vepesid), also known as R-EPOCH, may be used. Additional rounds of chemotherapy may be necessary for recurrent diffuse large B-cell lymphoma. Radiation therapy – Radiation therapy uses high energy sources, such as X-rays and protons, to kill cancer cells and can be used alone or in combination with other treatments. Radiation therapy for diffuse large B-cell lymphoma is directed at the affected lymph nodes and areas where the cancer may progress and may be repeated several times a week. Biologic therapy – Biologic therapy helps the body’s immune system attack and kill cancer cells. CAR T cell (chimeric antigen receptor T cells) therapies or monoclonal antibody therapies (Rituxan) or ibrutinib (Imbruvica) target areas on cancer cells and may be used in diffuse large B-cell lymphoma after two or more other treatments have been tried. Additional biologic therapies include radioimmunotherapy drugs made of monoclonal antibodies that carry radioactive isotopes that attach to cancer cells, delivering radiation directly to the cells, such as ibritumomab tiuxetan (Zevalin). For patients with recurrent diffuse large B-cell lymphoma after two prior therapies, a new drug, polatuzumab vedontin-piiq (Polivy), which is an engineered antibody attached to a chemotherapy drug, may be administered in combination with the chemotherapy agents, bendamustine and rituximab (BR). Bone marrow transplant (Stem cell transplant) – Bone marrow transplant, also known as stem cell transplant, may be available to selected patients, especially those with recurrence of diffuse large B-cell lymphoma, and uses high-dose chemotherapy and radiation first to suppress bone marrow (where blood cells are produced), and then healthy bone marrow stem cells from the patient (autologous stem cell transplant) are infused into the blood to help rebuild normal bone marrow and cells.

There are several online, local, national, and international support groups for diffuse large B-cell lymphoma, including the following: American Cancer Society - https://www.cancer.org/treatment/support-programs-and-services.html CancerCare - https://www.cancercare.org/diagnosis/diffuse_large_b-cell_lymphoma Leukemia and Lymphoma Society - https://www.lls.org/

The outcomes (prognosis) for diffuse large B-cell lymphoma vary, depending on the type, stage, the patient’s age and overall health, and the blood level of the enzyme, LDH, which increases tumor growth. While diffuse large B-cell lymphoma is an aggressive cancer, it can possibly be cured, with 3 out of 4 patients cancer-free after treatment, while half are cured. For many patients, diffuse large B-cell lymphoma does not recur after treatment.

Complications of diffuse large B-cell lymphoma are mainly treatment-related and may include weakness and fatigue, nausea, diarrhea, constipation, mouth sores, hair loss, low blood cell counts, fertility problems, heart damage, the development of leukemia or other cancers, and increased risk of fever and infection. Treatments for these cancer treatment-related side-effects are an essential part of cancer care.

If you experience any of the following symptoms of diffuse large B-cell lymphoma, such as swollen lymph nodes in the neck, underarm, or groin, extreme fatigue, weakness, unexplained weight loss, itchy skin or rash, night sweats, fever, pain in the chest, abdomen, or bones, make an appointment with your doctor as soon as possible.

There is no known way to prevent diffuse large B-cell lymphoma; however, the risk of developing this cancer can be decreased by preventing HIV infection and avoiding obesity.