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8 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.
An aggressive T-cell lymphoma, mostly of children and young adults, whose cells carry a broken ALK gene and a protein called CD30 on the surface. Despite looking alarming down the microscope it is the T-cell lymphoma most often cured, and both of its markers are things that drugs can aim at.
What it is. A lymphoma of T cells in which a piece of chromosome 2 carrying the ALK gene has joined another gene, most often NPM1 on chromosome 5, producing a fusion protein that is permanently switched on and drives the cell to divide. Every cell also carries CD30, strongly and uniformly, which is the second thing that makes this disease unusual.
How it differs from the rest of the family. WHO-HAEM5 recognises three anaplastic large cell lymphomas: this one, the ALK-negative form and the breast implant-associated form, with the primary cutaneous form filed among the skin lymphomas. ALK-positive disease has been separated from ALK-negative disease since the fourth edition because its cause and its course are different, and the difference is large: it occurs in much younger people and is cured far more often.
| Setting | Approach | Guideline |
|---|---|---|
| Making the diagnosis, and the mistake to avoid | Immunohistochemistry for CD30 and for ALK protein on the biopsy, with fluorescence in situ hybridisation to confirm the rearrangement where the stain is equivocal. The large pleomorphic cells, the frequent expression of epithelial membrane antigen and the loss of several T-cell markers mean that a tumour stained with a short panel can be reported as a carcinoma or a sarcoma; CD30 and ALK are what prevent that. Staging covers the sites this disease reaches outside the lymph nodes: skin, bone, soft tissue, lung and liver. | not mapped |
| First-line treatment | Brentuximab vedotin with cyclophosphamide, doxorubicin and prednisone, on the strength of ECHELON-2, which randomised 452 people with untreated CD30-positive peripheral T-cell lymphoma, three-quarters of them with systemic anaplastic large cell lymphoma: five-year progression-free survival 51.4 per cent against 43.0 and overall survival 70.1 against 61.0 with chemotherapy alone. Vincristine is left out because brentuximab vedotin is itself a tubulin-directed agent and giving both causes unacceptable nerve damage. Unlike the other nodal T-cell lymphomas, ALK-positive disease does well enough that consolidating a first remission with an autologous transplant is generally not offered. The regimens and the cycle detail are on the peripheral T-cell lymphoma page. | not mapped |
| Relapse | Brentuximab vedotin is highly active in relapsed systemic anaplastic large cell lymphoma, with response rates well above those seen in other peripheral T-cell lymphomas, and it is the usual choice for anyone who has not already had it. ALK inhibitors developed for lung cancer, crizotinib in particular, produce responses here and are used especially in children and young adults. Allogeneic transplant is offered to fit patients who respond. The detail is on the peripheral T-cell lymphoma page. | not mapped |