Korean J Hematol 2002; 37(1):

Published online March 31, 2002

© The Korean Society of Hematology

재생불량성빈혈 환자에서 항림프구 글로불린과 Cyclosporine A 병합요법 후 T 림프구 면역표현형 분석

박은정, 민우성, 민창기, 이석, 김동욱, 이종욱, 박수정, 김유진, 박윤희, 김춘추

가톨릭대학교 의과대학 조혈모세포이식센터

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

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

Catholic Hemopoietic Stem Cell Transplantation Center, College of Medicine, The Catholic University of Korea, Seoul, Korea

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-cytometry after gathering the peripheral blood from 17 aplastic anemia patients, who were treated with
a combining therapy of ALG and cyclosporine 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 donors 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). Reagarding 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 lymphocyte 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 wer believed to be the factors that caused marrow failure among others. The ratio between CD4+ T lymphocytes and 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.

Keywords Aplastic anemia; Antilymphocyte globulin (ALG);

Article

Korean J Hematol 2002; 37(1): 38-45

Published online March 31, 2002

Copyright © The Korean Society of Hematology.

재생불량성빈혈 환자에서 항림프구 글로불린과 Cyclosporine A 병합요법 후 T 림프구 면역표현형 분석

박은정, 민우성, 민창기, 이석, 김동욱, 이종욱, 박수정, 김유진, 박윤희, 김춘추

가톨릭대학교 의과대학 조혈모세포이식센터

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

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

Catholic Hemopoietic Stem Cell Transplantation Center, College of Medicine, The Catholic University of Korea, Seoul, Korea

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-cytometry after gathering the peripheral blood from 17 aplastic anemia patients, who were treated with
a combining therapy of ALG and cyclosporine 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 donors 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). Reagarding 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 lymphocyte 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 wer believed to be the factors that caused marrow failure among others. The ratio between CD4+ T lymphocytes and 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.

Keywords: Aplastic anemia, Antilymphocyte globulin (ALG),

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