Treatment of T Cell Large Granular Lymphocyte Leukemia with Reduced-Intensity Allogeneic Stem Cell Transplantation.

T cell large granular lymphocyte (LGL) leukemia is a lymphoproliferative disorder of clonal CD3-positive cytotoxic T cells. Clinical manifestations include neutropenia, anemia, thrombocytopenia, recurrent infections and splenomegaly. Two patients with refractory LGL leukemia were treated with an allogeneic stem cell transplantation following a reduced-intensity conditioning regimen. The first patient was a 54 yo female with transfusion dependent anemia and splenomegaly. Prior therapy included low dose methotrexate, cyclosporin A, equine antithymocyte globulin and alemtuzumab. The second patient was a 34 yo female with lymphocytosis and recurrent infections. Prior therapy included cyclosporin A and splenectomy. The hematopoietic cell source was related donor peripheral blood stem cells (5.79 x 10⁶ CD34+ cells/kg) for the first patient, and unrelated donor peripheral blood stem cells (8.04 x 10⁶ CD34+ cells/kg) for the second patient. The preparative regimen was fludarabine 30mg/m² daily on days −5, −4, −3; melphalan 140 mg/m² on day −2; the unrelated donor recipient also received rabbit antithymocyte globulin 6mg/kg in 3 divided doses on days −3, −2, −1. GVHD prophylaxis was provided with tacrolimus and methotrexate 5mg/m² on days +1, 3, 6, 11. Granulocyte engraftment >0.5/μL occurred on day +20 and +11; platelet engraftment >100/μL occurred on day +26 and +116 for the first and second patient respectively. The patient receiving the unrelated donor developed stage 1 skin GVHD and did not require systemic treatment. Patients achieved 100% donor chimerism by day 100. There was no chronic GVHD in either patient. Both patients achieved a complete remission and remain in CR, off immunosuppressive therapy, at 13 and 14 months post transplantation. Allogeneic transplantation using a reduced-intensity preparative regimen is an effective therapy for T cell large granular cell leukemia in patients who have failed prior therapy.