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10 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
Richter transformation is the sudden change of slow chronic lymphocytic leukaemia into a fast-growing lymphoma, usually of the diffuse large B-cell type. It is treated with lymphoma chemotherapy followed by a donor transplant where possible, and newer drugs such as pirtobrutinib, venetoclax combinations and bispecific antibodies are being tested because standard chemotherapy rarely cures it.
Suspected when a patient with CLL develops a rapidly enlarging node, fever, weight loss, a sharply rising lactate dehydrogenase or a new bright focus on PET-CT, and confirmed by excision biopsy of the hottest node. About 95 percent of cases are diffuse large B-cell lymphoma and the rest Hodgkin-type; the distinction that matters most is clonal relationship to the CLL, since the 80 percent of large-cell cases that share the CLL's immunoglobulin rearrangement carry TP53, NOTCH1, CDKN2A and MYC lesions and do badly, while clonally unrelated cases behave like ordinary de novo lymphoma. Transformation can occur on any therapy, including BTK inhibitors and venetoclax, and is sometimes the reason a CLL treatment seems to fail.
Standard treatment is anthracycline-based chemoimmunotherapy, R-CHOP or R-EPOCH, with responses in fewer than half of clonally related cases and remissions that are short unless consolidated by an allogeneic stem cell transplant, which offers long-term survival to a minority of fit patients who respond. Autologous transplant is an option in chemosensitive disease when no donor is available. Hodgkin-type transformation is treated with Hodgkin regimens and has a better outlook.
| Setting | Approach | Guideline |
|---|---|---|
| Diagnosis | Excision biopsy of the PET-hottest node, histology with clonality studies, TP53 and MYC testing; restage CLL and check for cause such as BTK inhibitor progression. | not mapped |
| Diffuse large B-cell type, first treatment | R-CHOP or R-EPOCH chemoimmunotherapy, with venetoclax added in trials; pirtobrutinib or a bispecific antibody in patients unfit for chemotherapy or within trials. | not mapped |
| Consolidation in responders | Allogeneic stem cell transplant for fit patients with a donor; autologous transplant where chemosensitive and no donor. | not mapped |
| Relapsed or chemotherapy-refractory | Clinical trial: bispecific antibodies (epcoritamab, glofitamab), BTK inhibitor with checkpoint inhibitor, CD19 CAR-T, pirtobrutinib; palliative care. | not mapped |