Clinical features of large granular lymphocyte leukemia
Section snippets
Spectrum of LGL proliferations: problem of nomenclature
Several terms have been used to describe LGL disorders including: lymphoproliferative disease of granular lymphocytes (LDGL), granular lymphocyte proliferative disorder (GLPD), and LGL leukemia. At least four distinct clinical syndromes can be identified (Fig 1), ranging from a reactive to an aggressive/life-threatening form.9, 42, 58, 59, 69, 70 The different entities may overlap, suggesting that a chronic benign form may possibly transform into an aggressive form.
Problems of definition
It is important to distinguish authentic LGL leukemia from the other forms of LGL lymphoproliferations. We originally described LGL leukemia as a disease characterized by clonal LGL expansion as documented by clonal cytogenetic abnormalities44 or T-cell receptor (TCR) gene rearrangement studies.42 The diagnosis of LDGL was initially based on LGL expansion greater than 2 × 109/L lasting more than 6 months.42 The definition needs some clarification: (1) Some patients have significant leukopenia
Clinical manifestations of T-LGL leukemia
There is no specific predilection for either men or women, and the elderly are mainly affected, with a median age of 60 years (range, 4 to 88).9, 35, 42, 58, 59, 69 Only 10% of patients are younger than 40 and pediatric cases are rare. About one third are asymptomatic at diagnosis. The frequency of symptoms is different among studies depending on the criteria used for patient selection. Initial manifestations are mainly related to neutropenia and include fever with recurrent bacterial
CD3− NK leukemia
About 15% of LGL proliferations have a CD3− NK phenotype.
Reactive and transient LGL proliferations
Different clinical situations may be associated with a transient excess of circulating LGL. Viral infections (EBV, hepatitis, cytomegalovirus), various skin disorders, idiopathic thrombocytopenic purpura, connectivitis, post-transplantation for organ or hematopoietic stem cells grafts, solid tumors, or non-Hodgkin’s lymphomas, and hemophagocytic syndromes are the main clinical situations where such LGL proliferations can be observed. Usually, the LGL count does not exceed 3 to 4 × 109/L, and
Conclusions
In summary, this review has highlighted the clinicobiological features of LGL leukemia and delineated the different forms of LGL proliferations. Progress has been made in the phenotypic and molecular analysis of LGL clones. However, the border between benign and malignant LGL expansion is not yet fully understood. Ongoing prospective clinical studies should optimize therapeutic approaches to T-LGL leukemia. The prognosis of NK LGL leukemia remains poor and further clinical trials are warranted.
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*Address correspondence to Thierry Lamy, MD, PhD, Department of Hematology, Service d’Hématologie, Hôpital Pontchaillou, CHU de Rennes, 35033, Rennes, France