{"entity":{"id":"t-large-granular-lymphocytic-leukaemia","kind":"cancer","name":"T-cell large granular lymphocytic leukaemia","aka":["Large granular lymphocytic leukemia","Large granular lymphocytic leukaemia","LGL leukaemia","T-LGL leukaemia","T-LGLL","Chronic lymphoproliferative disorder of NK cells (related NK-cell form)"],"tldr":"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.","summary":"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).\n\nHow 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.\n\nHow common: no registry figure in the sources read.\n\nTreatment: observation without cytopenias or symptoms; low-dose oral methotrexate, cyclosporin or cyclophosphamide when treatment is indicated, used sequentially; salvage with alemtuzumab, JAK inhibitors, splenectomy or abatacept; the PI3K-delta inhibitor and anti-CD94 antibody trials linked here (Leukemia and Lymphoma 2018).","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Large_granular_lymphocytic_leukemia","links":[{"label":"NCI PDQ: chronic lymphocytic leukaemia treatment","url":"https://www.cancer.gov/types/leukemia/patient/cll-treatment-pdq"},{"label":"Alaggio 2022, Leukemia: the 5th edition WHO classification of haematolymphoid tumours, lymphoid neoplasms","url":"https://doi.org/10.1038/s41375-022-01620-2"},{"label":"Koskela 2012, NEJM: somatic STAT3 mutations in large granular lymphocytic leukaemia","url":"https://doi.org/10.1056/nejmoa1114885"},{"label":"Leukemia and Lymphoma 2018: clinical features and treatment outcomes in 204 patients with large granular lymphocytic leukaemia","url":"https://doi.org/10.1080/10428194.2017.1339880"}],"tags":["subtype-page","wave4","haematologic","rare"],"related":["leukaemia","t-cell-prolymphocytic-leukaemia","hepatosplenic-t-cell-lymphoma","cll"],"cancers":[],"sections":[],"technologies":[],"targets":["stat3"],"drugs":["methotrexate","cyclophosphamide","alemtuzumab","ruxolitinib"],"companies":[],"institutions":[],"pathways":["jak-stat"],"terms":[],"trials":["nct06224257","nct05475925"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"haematologic","burden":"Rare and chronic; the largest treatment series holds 204 patients meeting uniform criteria, followed for a median of 36 months (Leukemia and Lymphoma 2018). No registry figure is in the sources read.","subtypes":["T-cell large granular lymphocytic leukaemia, STAT3-mutated (40 percent; more often symptomatic)","T-cell large granular lymphocytic leukaemia, STAT3 wild-type (STAT5B in a minority)","Large granular lymphocytic leukaemia with rheumatoid arthritis or Felty syndrome","Chronic lymphoproliferative disorder of NK cells (related)"],"biomarkers":["Clonal T-cell receptor rearrangement with increased large granular lymphocytes","STAT3 SH2 domain mutations (Y640F, D661V, D661Y, N647I)","Neutrophil count and haemoglobin (treatment indication)","Rheumatoid factor and autoimmune screen"],"standardOfCare":[{"setting":"Symptomatic or cytopenic","approach":"Low-dose methotrexate, cyclosporin or cyclophosphamide, used sequentially; salvage with alemtuzumab, JAK inhibitors or splenectomy.","refs":["methotrexate","cyclophosphamide","alemtuzumab","ruxolitinib","leukaemia"]}],"stateOfArt":[],"history":[],"pipeline":[],"openProblems":[],"parent":"leukaemia"},"route":"/cancers/t-large-granular-lymphocytic-leukaemia/","neighbours":{"cancer":[{"id":"cll","kind":"cancer","name":"Chronic lymphocytic leukaemia","route":"/cancers/cll/"},{"id":"hepatosplenic-t-cell-lymphoma","kind":"cancer","name":"Hepatosplenic T-cell lymphoma","route":"/cancers/hepatosplenic-t-cell-lymphoma/"},{"id":"leukaemia","kind":"cancer","name":"Leukaemia (all types)","route":"/cancers/leukaemia/"},{"id":"t-cell-prolymphocytic-leukaemia","kind":"cancer","name":"T-cell prolymphocytic leukaemia","route":"/cancers/t-cell-prolymphocytic-leukaemia/"}],"target":[{"id":"stat3","kind":"target","name":"STAT3","route":"/targets/stat3/"}],"drug":[{"id":"alemtuzumab","kind":"drug","name":"Alemtuzumab","route":"/drugs/alemtuzumab/"},{"id":"cyclophosphamide","kind":"drug","name":"Cyclophosphamide","route":"/drugs/cyclophosphamide/"},{"id":"methotrexate","kind":"drug","name":"Methotrexate","route":"/drugs/methotrexate/"},{"id":"ruxolitinib","kind":"drug","name":"Ruxolitinib","route":"/drugs/ruxolitinib/"}],"pathway":[{"id":"jak-stat","kind":"pathway","name":"JAK-STAT signalling","route":"/pathways/jak-stat/"}],"trial":[{"id":"nct05475925","kind":"trial","name":"A Study of DR-01 in Subjects With Large Granular Lymphocytic Leukemia or Cytotoxic Lymphomas","route":"/trials/nct05475925/"},{"id":"nct06224257","kind":"trial","name":"Efficacy and Safety of Linperlisib in Relapsed/Refractory Large Granular T Lymphocytic Leukemia","route":"/trials/nct06224257/"}]}}