T-cell large granular lymphocyte (T-LGL) leukemia is a rare indolent lymphoproliferative disorder diagnosed by presence of >2,000/μL peripheral CD3+CD8+CD16+/−CD56 +/−CD57+ LGL and/or evidence of T-LGL clonality by T-cell receptor (TCR) gene rearrangement, accompanied by neutropenia and/or other cytopenias. We reported the efficacy of cyclosporin A (CsA) in the treatment of LGL-associated neutropenia [

] and we report here long-term follow-up of our larger patient (pt) cohort. Between 1982 and 2006, 18 pts were diagnosed with T-LGL leukemia with the above strict criteria (M:F 11:7; median age, 67; range, 48–84 years). Mean follow-up from diagnosis is 59 (range, 2–303) months. Autoimmune phenomena were present in 6 (33%), including pure red cell aplasia in two, lymphocytic colitis and ascites in one, and erosive osteoarthritis and pulmonary granulomatous vasculitis in one other. Splenomegaly was present in 6 (33%). Median (range) hemoglobin (Hb), absolute neutrophil count (ANC) and platelet count were 10.4 (3.6–15.5) g/dL, 1,100 (0–5,900)/μL and 152,000 (69,000–583,000)/μL. Anemia, neutropenia (ANC<1,000/μL), severe neutropenia (ANC<500/μL) and thrombocytopenia were present in 9 (50%), 13 (72%), 6 (33%), and 5 (28%), respectively. Four (22%) had one cytopenia, ten (56%) bicytopenia and one (6%) pancytopenia. Median (range) absolute number and percentage of peripheral LGL by flow cytometry were 1,147 (59–9,327)/μL and 31 (3.3–66.9) %. TCR gene rearrangement was present in 16 (89%). Fourteen pts (78%) required treatment early; median treatment-free survival was only 1.0 (95% CI, 0–8.4) months. Indications for initiation of treatment included Hb<9 g/dL, ANC<500/μL, ANC<1,000/μL with recurrent infections and platelet count<50,000/μL. CsA was initiated in 11 pts (61%). The median duration of CsA therapy was 47 (range, 4.5–186) months. Four pts were still receiving CsA at last follow-up. Four pts (40%) achieved sustained complete hematologic improvement (HI) by MD Anderson response criteria [Leuk Res 2007;31:939–45], 1 (10%) major HI and 2 minor HI (20%), resulting in an overall HI of 70%. One other (10%) had mixed HI and 2 (20%) had progressive disease. G-CSF was initiated simultaneously with, and added later to, CsA in 1 (10%) and 2 (20%) pts, respectively, and erythropoietin (Epo) in 1 (10%) and 3 (30%), respectively. The addition of growth factor resolved neutropenia and/or anemia in two additional pts, resulting in overall and complete HI of 80% and 50% respectively. Median time (range) to maximum HI with CsA, G-CSF and Epo were 2.5 (0.2–27), 0.7(0.6–1.9) and 1.5 (0.9–1.9) months, respectively. Renal insufficiency, hypertension and/or hypomagnesemia occurred in 7 (70%). CsA tapering and discontinuation were successful in two (40%) of the five pts who achieved complete HI, 91 and 186 months after initiation. Four pts (22.2%) have not required any treatment 8, 8, 33 and 80 months after diagnosis, and two received Epo and one HIV therapy alone. All except one were alive at the mean follow-up time of 59 (range, 2–303) months and median survival has not been reached. Thus T-LGL leukemia usually requires treatment early after diagnosis, but has an excellent prognosis. CsA with or without growth factor support is an effective treatment, leading to overall and complete HI in 80% and 50%, respectively. Successful tapering and discontinuation of therapy may be possible in 40% of pts who achieve long-term complete HI.

Author notes

Disclosure:Off Label Use: The use of cyclosporin A in large granular lymphocyte leukemia therapy is an off-label use of this drug. However, there have been several reports of this use with excellent safety profile.