Treatment of chronic neutropenia associated with large granular lymphocytosis with cyclosporine a and filgrastim

Abstract

A patient with neutropenia and life-threatening infections secondary to T-gamma lymphoproliferative disease, who did not respond to treatment with recombinant human G-CSF (filgrastim), was treated with filgrastin plus cyclosporine A (CyA). The patient achieved a good response in the absolute neutrophil count and subsequently required a dose reduction in the filgrastim. The patient was eventually discontinued from the CyA but continues on filgrastim alone. While on therapy, the large granular lymphocytes disappeared from the circulation and the beta-TCR rearrangement, which was present prior to beginning therapy, became undetectable. The patient had no significant toxicity to the CyA or the filgrastim and he has not experienced any serious infections or required hospitalization. Filgrastim has proven to be relatively nontoxic and of some benefit to patients with this disease and should probably be utilized first when treatment is necessary. However, if improvement is not observed, these findings suggest that a trial of the combination of CyA plus filgrastim may be beneficial.

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].…”

Induction of clinical remission in T-large granular lymphocyte leukemia with cyclosporin A, monitored by use of immunophenotyping with Vβ antibodies

“…[12][13][14][15] Although low-dose methotrexate was recently demonstrated to be effective in 50% of patients with T-LGL leukemia (n = 10), 16 further evaluation of cyclosporin A treatment in LGl appears to be of interest.…”

Treatment of refractory large granular lymphocytic leukemia with 2-chlorodeoxyadenosine

“…Although LGL leukemia is frequently described as an indolent disorder, profound neutropenia with consequent sepsis and death are frequent [1]. Treatment of the disorder is largely anecdotal and has consisted primarily of immunosuppressive regimens with prednisone [1], low-dose methotrexate [3], and cyclosporine [4]. G-CSF has also been used [5].…”