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5 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.
T-cell large granular lymphocytic leukaemia is a slow, usually non-fatal leukaemia in which a clone of cytotoxic T cells builds up in the blood and marrow and turns the immune system against the body, causing low neutrophil counts, anaemia and often rheumatoid arthritis. It is treated only when it causes problems, with low-dose immune-suppressing drugs rather than chemotherapy.
WHO-HAEM5 keeps T-cell large granular lymphocytic leukaemia as a mature T-cell leukaemia of clonal CD3-positive CD8-positive cytotoxic lymphocytes, beside the related chronic lymphoproliferative disorder of NK cells (Alaggio 2022). Exome sequencing found somatic STAT3 mutations in 31 of 77 patients (40 percent), all in the SH2 domain (Y640F 17 percent, D661V and D661Y 9 percent each, N647I 4 percent), causing STAT3 phosphorylation and nuclear localisation; the disease is often associated with autoimmune disorders and immune-mediated cytopenias (Koskela 2012). In 204 patients, therapy was needed mostly for anaemia and neutropenia; methotrexate, cyclosporin and cyclophosphamide each gave overall responses of 40 to 50 percent, sequential use responded in most, only 10 to 20 percent needed salvage (antithymocyte globulin, alemtuzumab, tofacitinib, splenectomy or abatacept), methotrexate gave the most durable responses, and STAT3-mutated patients needed therapy more often but had better overall survival (Leukemia and Lymphoma 2018).
How it differs from its parent: it is indolent and immune-mediated rather than proliferative; its harm comes from cytopenias and autoimmunity, not from tumour bulk; and its treatment is immunosuppression, with JAK-STAT inhibition the rational new direction from the STAT3 findings.
| Setting | Approach | Guideline |
|---|---|---|
| Symptomatic or cytopenic | Low-dose methotrexate, cyclosporin or cyclophosphamide, used sequentially; salvage with alemtuzumab, JAK inhibitors or splenectomy. | not mapped |