Rapid response to cyclosporine therapy and sustained remission in large granular lymphocyte leukemia [letter]

Abstract

Considering the recent interest in large granular lymphocyte (LGL) proliferation and the frequent association of severe granulopenia ("T-y neutropenia") with T-LGL leukemia leading to intractable and often fatal infections, we wish to describe a case of T-LGL leukemia with absolute agranulocytosis which showed an excellent, rapid, and sustained response to nontoxic doses of cyclosporine after failing steroid and growth-factor therapy. CASE REPORT A 36-year-old woman was admitted to Cedars-Sinai Medical Center in Los Angeles in December 1993 because of agranulocytosis associated with intractable fever and resistant staphylococcus septicemia not responding to polyantimicrobial therapy. Nine months before admission, she developed a severe upper respiratory infection associated with myalgia, arthralgia, weakness, fatigue, and other systemic symptoms. Repeated blood counts were within normal range (white blood cell [WBC] count 6.5 to 7.7 X IO3&) with slight lymphocytosis. The absolute neutrophil count (ANC) was between 2.9 and 3.6 X 103/L. There was no evidence of rheumatoid arthritis or other collagen diseases. Five months before admission, she developed shaking chills, 104°F fever, and pneumonia that required prolonged antibiotic therapy. Anemia and absolute neutropenia (ANC decreasing from 1.9 to 0.8 X 103/L) was observed, and she was treated with ferrous sulfate and prednisone without hematologic response. From this point on, the patient experienced increasingly frequent episodes of respiratory infections, sepsis, acneiform dermatitis, abscesses, and other infectious problems. One month before admission, the patient was again hospitalized at a community hospital with fever, chills, pneumonia associated with chest-wall pain, generalized muscle aches, and joint pain diagnosed as fibromyalgia. Blood counts showed the ANC persistently below 500; the bone marrow showed markedly reduced granulocyte precursors. Treatment with high-dose prednisone, granulocyte-macrophage colony-stimulating factor (GM-CSF), G-CSF, and antibiotics had no effect. She became delirious and was transferred to Cedars-Sinai Medical Center. On admission, the patient exhibited chills, rigor, 103°F fever, perioral ulcerative herpes (HSV l), ulcerative stomatitis, pharyngitis, and swollen large joints. Examination revealed no lymphadenopathy or splenomegaly. Subsequent cultures yielded no growth while on antibiotic therapy. The total WBC count was 0.6 X 103/L with 98% lymphocytes and 2% eosinophils; neutrophils and monocytes were absent from the blood film, and 70% of the lymphocytes exhibited large granular morphology with pale blue cytoplasms and multiple azurophilic granules. The hemoglobin and hematocrit was 9.0 g and 27.7%; the platelet count was 130,000; the reticulocyte count was 2.6% (Table l). A Coombs test was positive, ANA (antinuclear antibodies) was negative, the lactate dehydrogenase (LDH) was elevated, and serum protein electrophoresis, quantitative Igs, serum B12, and serum folic acid levels were within normal range. Immunofixation el...

Large granular lymphocyte leukemia with pure red cell aplasia in a renal transplant recipient

“…Immune suppressive agents, such as CyA, cyclophosphamide, methotrexate, prednisolone, antithymocyte globulin, myleran, azathiopurine, and chrombucil, are the treatment options for patients with PRCA and LGL leukemia. CyA is often used in these patients [7][8][9][10][11][12][13][14], and as an immunosuppressive agent, is believed to inhibit the production of interleukin (IL)-2 and ␥ interferon (IFN) by T-lymphocytes, as well as the activation of cytotoxic T-cells by IL-2 [21]. Both IL-2 and ␥ IFN have been shown to inhibit the growth of hematopoietic progenitor cells [22].…”

“…Large granular lymphocyte (LGL) leukemia is a clonal disorder of T-cells or natural killer cells and is often associated with pure red cell aplasia (PRCA) [6,7]. CyA is an effective treatment for LGL leukemia and PRCA [7][8][9][10][11][12][13][14].…”

T‐cell large granular lymphocyte leukemia

“…Again, synergism with growth factors was documented. Single case reports19, 23, 24, 26 also support the efficacy of CSA and recognize persistence of the LGL clone despite treatment.…”

“…Complete and durable remissions in our series were associated with BM clearance. Evaluation of the effects of CSA and MTX on BM not only confirmed the lack of a correlation between BM disease and hematologic parameters, but also confirmed the underlying resistance of the LGL clone to eradication19, 21, 23–26 and highlighted the importance of immunosuppression rather than cytotoxicity in its management.…”

“…Correction of cytopenias with therapy may be achieved without eradication of the clone,19–26 which often is resistant to treatment. Furthermore, complete normalization of the neutrophil count is not essential for symptomatic improvement.…”