Analysis of T Lymphocyte Subsets Following Antilymphocyte Globulin and Cyclosporine A Therapy in Patients with Aplastic Anemia

Park, Eun Joung; Min, Woo Sung; Min, Chang Ki; Lee, Seok; Kim, Dong Wook; Lee, Jong Wook; Park, Soo Jeong; Kim, Yoo Jin; Park, Yoon Hee; Kim, Chun Choo

Abstract

BACKGROUND: Immunosuppression of hematopoiesis has been regarded as one of the most important pathogenetic mechanisms of idiopathic aplastic anemia. This investigation intended to examine the immunological pathogenesis of aplastic anemia and discover the therapeutic mechanism and predictor factors for the combined therapy of antilymphocyte globulin (ALG) and cyclosporine A through observing the changes of T lymphocyte subsets in the peripheral blood before and after the combining therapy of ALG and cyclosporine A.
METHODS
Comparisons and analyses were made after measuring CD4+ T-lymphocytes and CD8+ T-lymphocytes by the flow-cyto metry after gathering the peripheral blood from 17 aplastic anemia patients, who were treated with a combining therapy of ALG and cyclo sporine A at the Hematopoietic Stem Cell Transplatation Center of St. Mary's hospital, Catholic University, from August 2000 through November 2000. These were conducted prior to treatment, immediately after the therapy and 3 months later. Fifteen healthy bone marrow do nors were selected as a normal control group.
RESULTS
With respect to comparing T lymphocyte subsets between the aplastic anemia patient group and the normal control group in the peripheral blood, the CD4+ T lymphocytes ratio and the absolute numbers decreased significantly for the aplastic anemia patient group, as opposed to that of the normal control group (P=0.0001, P=0.0003). The CD8+ T lymphocytes ratio and the absolute numbers increased significantly for the response group (complete response group and partial response group) than that of the control group (P=0.0003, P=0.0295). Regarding the ratio of CD4+ T lymphocytes to CD8+ T lymphocytes, the aplastic anemia patients group showed a significant decrease comparing to that of the control group with 0.79+/-0.32 and 1.41+/-0.24 respectively (P=0.0001). The therapyresponding rate for ALG and cyclosporine A was 70.59% (complete response rate, 23.53%; partial response rate, 47.06%). There were no critical complications to be considered as limiting factors for the therapy. The CD8+ T lymphocytes ratio and absolute numbers already increased before the therapy for the better response group (P=0.0001, r=0.791; P=0.008, r=0.616). The ratio between CD4+ T lymphocytes and CD8+ T lymphocytes was decreased comparing the other two groups as 0.57+/-0.18 in the complete response group before the treatment was implemented. However, there was no statistically significant difference (P=0.30). The ratio of CD8+ T lymphocytes 3 months after the therapy decreased by three-folds in the response group as compared with that of the non-response group before the therapy. The ratio between CD4+ T lymphocytes and CD8+ T lymphocytes improved more than that of the other two groups (1.00+/-0.70) for the complete response group (P=0.0046).
CONCLUSION
The imbalance of the lympho cyte subset shown as the ratio between the CD4+ T lymphocytes and the CD8+ T lymphocytes decreased secondary to the decrease of CD4+ T lymphocytes as well as the increase of CD8+ T lymphocytes were believed to be the factors that caused marrow failure among others. The ratio between CD4+ T lymphocytes and CD8+ T lymphocytes can be improved by removing CD8+ T lymphocytes, which increased by the combining therapy of ALG and cyclosporine A. These results may help predict the therapeutic effects by way of analyzing the T-lymphocyte subsets in the peripheral blood prior to implementing the therapy.