Long-Term Follow-Up of Patients with T-Large Granular Lymphocyte Leukemia (T-LGL); Experience in a Single Institution.

T-LGL is a clonal indolent lymphoid leukemia characterized by accumulation of large granular T-cells and cytopenias. We have identified 21 patients with T-LGL who were seen at the MD Anderson Cancer Center between 1997 and 2005. The median age at diagnosis was 53.5 years (range 34 to 72) without a male or female predilection. Fourteen patients (67%) were asymptomatic at diagnosis. Five patients (24%) presented with fatigue secondary to anemia; 1 (5%) had symptomatic splenomegaly and 1 presented with a diverticular abscess. Eighty percent of the patients presented with anemia with median hemoglobin of 9.9g/dl (range 7.4 to12.9 g/dl), 47% with neutropenia with a median absolute neutrophil count of 975/ul (range 110 to 5600/ul), and 38% had thrombocytopenia with a median platelets count of 61.5 x 10⁹/l (range18 to 135 x 10⁹/l). Six patients (29%) had splenomegaly, 3 (14.2%) had hepatomegaly and 1 had retroperitoneal lymph node enlargement on CT. During the course of follow-up (median 19 months, range 2–78 months), 11 patient (52%) developed constitutional symptoms. Six patients had recurrent infections including upper respiratory infections, pneumonia, and folliculitis unrelated to initiation of treatment. Associated autoimmune conditions included rheumatoid arthritis in 3 patients (14%) and hemolytic anemia in one patient. Only two patients had cytogenetic abnormalities, both including abnormalities involving chromosome 6. Monoclonal T cell receptor gamma chain gene rearrangements were detected by PCR analysis in 17 of 18 evaluable patients. Immunophenotypic studies revealed 16 patients to be CD4−/CD8+, 3 CD4−/CD8−, 1 CD4+/CD8+, and 1 CD4+/CD8−. CD56 was positive in 1 patient and none expressed CD26. Five patients (24%) have required no therapy, and remain asymptomatic with a median follow up of 67 months (range 5 to 78). Three patients received erythropoietin or G-CSF with some improvement. Nine patients (43%) were treated with cyclosporine, 2 achieving a response, 2 with stable disease, 3 with progression, and 2 were lost follow up. One of the 3 patients with disease progression had splenectomy and 1 was treated with infliximab; both responded. Combination of pentostatin and alemtuzumab was used in 2 patients with no improvement in the cytopenias; therapy was discontinued in both due to worsening of cytopenias and infections. Other treatment modalities included alemtuzumab alone in 1 patient with no improvement, fludarabine in 1 with minor response, combination of fludarabine and cyclophosphamide in 1 with minor response, methotrexate in 2 with no response and splenectomy in 3 with response and no requirements for further intervention. We conclude that T-LGL generally has an indolent course with no need for active therapy; patients with progressive cytopenias or refractory disease may benefit from splenectomy. New treatment modalities are needed.