Clinicopathologic Features and Efficacy of Immunosuppressive Therapy in T-Cell Large Granular Lymphocytic Leukemia.

Large granular lymphocytic leukemia (LGLL) comprises a spectrum of rare clonal lymphoproliferative neoplasm that evolves from either CD3+ cytotoxic T-cells (T-LGLL) or CD3- natural killer cells (NK-LGLL). T-LGLL accounts for 85% of all cases and is the most common type of LGLL diagnosed in Western countries. Our understanding of clinical and pathologic characteristics and therapeutic outcomes is limited to a few retrospective single institutional studies and case reports. The main objective of this study was to review the clinical and laboratory characteristics, management and outcome of patients (pts) with LGLL.

Eighty-five consecutive patients diagnosed with T-LGLL between April 1999 and June 2009 was identified in our institutional LGLL database. Clinical and laboratory data, treatment regimens and responses were analyzed. Responses to treatment were assessed according to the modified IWG criteria for myelodysplastic syndromes (MDS). Asymptomatic patients were closely observed with laboratory studies. Pts with cytopenias received immunosuppressive therapy. The majority of patients received a monotherapy with methotrexate (MTX) 10mg/m² weekly, cyclophosphamide (CTX) 50-100mg po daily or cyclosporine A (CSA) 3-5 mg/kg po daily according to our treatment algorithm for LGLL. Treatment duration was at least 4 months before responses were assessed. Non-responders could cross-over to alternative agent. Six pts were excluded from the treatment analysis due to an insufficient follow-up data.

Median age of pts was 61 (range, 32 – 85) yrs. M/F ratio was 1.3. The median duration of follow-up was 1106 (range, 114 – 2652) days. Sixty-six (78%) pts manifested most common immunophenotype: CD3+CD8+CD57+TCRalpha/beta. TCR beta or gamma (or both) genes were clonally rearranged in 75 (88%) pts. Anemia was observed in 42 (50%), severe anemia with Hb<8g/dl in 4 (5%), neutropenia in 37 (44%) and severe neutropenia (ANC <0.5 × 10 9.) in 15 (18%) pts. Twenty-one (25%) pts presented with thrombocytopenia (platelets <100 × 10 9). Thirty-three (28%) pts had splenomegaly, 1 (1%) hepatomegaly, and 4 (5%) adenopathy. The most common autoimmune diseases associated with LGLL were rheumatoid arthritis in 14 (16%) and pure red cell aplasia in 6 (7%) pts. Ten (12%) pts were diagnosed with other hematologic malignancies such as diffuse large B cell lymphoma (2), peripheral T cell lymphoma, NOS (1), aplastic anemia (1), and Hodgkin's lymphoma (1). Thirteen (15%) pts were diagnosed with solid tumors. Two (1.5%) pts were positive for HIV-1 and none demonstrated HTLV-1/2 seropositivity. Of the 79 pts evaluable for treatment responses 56 (71%) received therapy. Twenty-three (29%) pts remained asymptomatic with stable hematologic parameters with the median time to follow-up 385 days. Pts treated with either MTX, CTX or CSA monotherapy as the 1^{st –} 3^rd line regimens demonstrated overall response rate (ORR) 84% with 64% CR and 20% PR. Five (9%) pts received other therapy and obtained CR. The median duration of CR was 119 (range, 28 – 1756) days.

This study demonstrates that immunosuppressive therapy can control cytopenias in more than 60% of pts with indolent T-LGLL.

No relevant conflicts of interest to declare.