• Double-hit / high-grade B-cell lymphoma: Double-hit lymphoma is a large B-cell lymphoma with rearrangements of two oncogenes (MYC plus BCL2 and/or BCL6), which behaves aggressively and often escapes R-CHOP.
• International Prognostic Index (IPI): A five-point score (age, stage, performance status, LDH, extranodal sites) that predicts how risky a lymphoma is before treatment.
• CNS prophylaxis in aggressive B-cell lymphoma, and the evidence against it: Some people with aggressive lymphoma are given extra methotrexate, into the spine or into a vein, to stop the lymphoma reaching the brain.
• R-CHOP (lymphoma chemoimmunotherapy): R-CHOP is the standard first treatment for diffuse large B-cell lymphoma: rituximab (an antibody against CD20) plus four chemotherapy drugs (cyclophosphamide, doxorubicin, vincristine, prednisone), given every three weeks for six cycles with curative intent.
• Indolent and aggressive lymphoma: Lymphomas are split by how fast they grow, and the split decides what happens next.
• The two lymphoma classifications of 2022 (WHO-HAEM5 and ICC): Since 2022 there have been two reference classifications of lymphoma rather than one, published within months of each other by overlapping groups of experts.
• The lymphoma regimen alphabet: R-CHOP, pola-R-CHP, DA-EPOCH-R, ABVD, BEACOPP and the rest: Lymphoma treatment is written in acronyms, one letter per drug.

Making the diagnosis: Every aggressive B-cell lymphoma biopsy is tested by fluorescence in situ hybridisation for MYC, and if MYC is rearranged, for BCL2 and BCL6. A lymphoma cannot be identified as double-hit by appearance, by immunohistochemistry for MYC and BCL2 protein, or by the cell-of-origin assay; dual protein expression is a separate and much commoner finding with its own, lesser, prognostic weight. Follicular lymphoma is excluded from the entity by both classifications even when it carries both rearrangements.

Biomarker results to ask for: MYC rearrangement and BCL2 rearrangement, both by fluorescence in situ hybridisation; the diagnosis cannot be made without them, BCL6 rearrangement, reported separately because the 2022 classifications moved MYC with BCL6 out of this entity, Germinal-centre B-cell phenotype: CD10 positive, BCL6 positive, MUM1 usually negative, The double-hit gene expression signature (DHITsig or MHG), measurable on a NanoString panel, which marks a larger group than the rearrangements do, Dual expression of MYC and BCL2 protein by immunohistochemistry, which is a different and much commoner finding and is not this entity.

Scans and tests linked to this cancer: FDG PET, Histopathology & immunohistochemistry.

Bring copies of scan reports, pathology and blood results, and a list of every medicine and supplement.

• Treatment, and what is known about it: Treated more intensively than diffuse large B-cell lymphoma, and with prophylaxis against disease in the brain and spinal cord, which is more frequent here. There has never been a randomised trial confined to this entity: the intensified regimens in use were adopted from retrospective comparisons after the group was shown to do less well with standard immunochemotherapy. The regimens, the doses and the evidence behind each are on the diffuse large B-cell lymphoma page and in the treatment layer of this family. (Diffuse large B-cell lymphoma, Rituximab, CNS prophylaxis in aggressive B-cell lymphoma, and the evidence against it, The lymphoma regimen alphabet: R-CHOP, pola-R-CHP, DA-EPOCH-R, ABVD, BEACOPP and the rest, R-CHOP (lymphoma chemoimmunotherapy))

From the standard of care recorded for this cancer; which apply depends on your stage and biomarkers. Ask which the team recommends and why.