Large granular lymphocytic leukaemia pathogenesis and management

Abstract

SummaryThe WHO classification recognises three distinct disorders of large granular lymphocytes: T‐cell large granular lymphocytic leukaemia (T‐LGL), chronic lymphoproliferative disorders of NK‐cells (CLPD‐NK) and agressive NK‐cell leukaemia. Despite the different cell of origin, there is considerable overlap between T‐LGL and CLPD‐NK in terms of clinical presentation and therapy. Many patients are asymptomatic and do not require treatment. Therapy, with immunosuppressant agents such as low dose methotrexate or ciclosporin, is usually indicated to correct cytopenias. In contrast, aggressive NK‐cell leukaemia and the rare CD56+ aggressive T‐LGL leukaemia follow a fulminant clinical course, affect younger individuals and require more intensive combination chemotherapy followed by allogeneic stem cell transplant in eligible patients. The relative rarity of these disorders means that there have been few clinical trials to inform management. However, there is now considerable interest in the pathogenesis of the chronic LGL leukaemias and this has stimulated early trials to evaluate novel agents which target the dysregulated apoptotic pathways characteristic of this disease.

Indolent T-cell large granular lymphocyte leukaemia after haematopoietic SCT: a clinicopathologic and molecular analysis

“…There were no associated cytopenias or autoimmune phenomena typically found in de novo T-LGL leukaemia. 14 The LGL counts had remained stable for long periods, up to ten years in one patient, without evidence of disease progression or organ infiltration. Therefore, although the diagnosis as stipulated by WHO criteria was T-LGL leukaemia, the clinical presentation was different from de novo T-LGL leukaemia, 1 --4 suggesting that a different pathological process might be involved.…”

Pathophysiologic mechanisms and management of neutropenia associated with large granular lymphocytic leukemia

“…This is a rare disorder characterized by periodic oscillations of the blood neutrophil count, the mechanism of which remains unknown. Finally, indolent LGL leukemia has often been associated with other hematological disorders, including chronic lymphocytic leukemia, monoclonal gammopathy of undetermined significance, multiple myeloma, hairy cell leukemia, paroxysmal nocturnal hemoglobinuria and, as previously mentioned, MDS and AA [14,25]. Such disorders could also be implicated in the pathogenesis of neutropenia.…”

“…Apart from viral antigen(s), an autoantigen has alternatively been proposed as the initial immune insult [5,14,25] and such a possibility might explain the close association between T-LGL and autoimmune disorders, such as rheumatoid arthritis (RA), systemic lupus erythematosus, Hashimoto's thyroiditis and other immune-mediated cytopenias, such as aplastic anemia (AA) and myelodysplasic syndrome (MDS) [14]. Interestingly, RA occurs in approximately 30% of patients with T-LGL leukemia [4,26].…”

Atypical aleukemic presentation of large granular lymphocytic leukemia: a case report

“…Despite the different cellular origin, there is considerable overlap between T-LGLL and CLPD-NK in terms of clinical presentation and response to therapy 6,7…”