Diffuse large B-cell lymphoma (DLBCL)

A biopsy is the only way to confirm lymphoma. Most often a surgeon removes a whole swollen lymph node or a piece of one (an excisional or incisional biopsy). This almost always gives enough tissue to name the exact type. A needle sample may not. The U.S. National Cancer Institute (NCI) advises that a lab doctor with lymphoma experience (a hematopathologist) review the sample.

The lab looks for markers on the cells with special stains (immunohistochemistry) and a cell-sorting test (flow cytometry). It also looks for gene and chromosome changes, often with a test called FISH. FISH can show whether the MYC, BCL2 and BCL6 genes are rearranged. If both MYC and BCL2 are rearranged, the lymphoma gets a different name (double-hit lymphoma). The lab may also report whether the cells look like germinal center or activated B cells (cell of origin).

The care team then checks how far the lymphoma has spread (staging). Tests often include a PET-CT scan, blood counts and an LDH level, plus tests for hepatitis B, hepatitis C and HIV. Some people also have a bone marrow biopsy, a spinal tap (lumbar puncture) or a heart scan before chemotherapy. FISH results usually come back within a couple of days. Full chromosome tests can take a week or more.

First-line treatment commonly combines an anti-CD20 antibody such as rituximab with chemotherapy. For advanced-stage disease, the usual choices are the drug combinations R-CHOP or Pola-R-CHP. In Pola-R-CHP, a medicine called polatuzumab vedotin takes the place of vincristine, one of the drugs in R-CHOP. Choice depends on disease characteristics, stage, health and treatment goals.

For primary refractory disease or an early relapse, approved CD19 CAR-T treatments are important standard options for eligible patients. They use modified T cells, generally collected from the patient, to recognize and attack lymphoma.

For later relapse that responds to salvage treatment, high-dose chemotherapy with autologous stem cell rescue remains an established option. Other targeted agents, bispecific antibodies and clinical trials can be useful depending on prior therapy. Allogeneic transplantation has a more selected role, often after other approaches have failed.

Many people with DLBCL are cured. NCI says most people with localized disease can be cured. It also says about half of people with advanced-stage disease are cured with rituximab and doxorubicin-based chemotherapy.

Outlook depends on things doctors can measure at diagnosis. A score called the International Prognostic Index (IPI) counts age, stage, how well the person manages daily activities, the LDH blood level, and spread to organs outside the lymph nodes. Rearranged MYC and BCL2 genes point to a poorer outlook.

Response to first treatment matters a great deal. NCI notes that people who stay free of DLBCL for 2 years then have about the same survival as others their age and sex. If the lymphoma does not respond or returns within a year, U.S. transplant experts (ASTCT) prefer CAR-T cell therapy for eligible people. For later relapses that respond to more chemotherapy, they recommend a transplant with the person's own stem cells.