[Selective elimination of alloreactive donor lymphocytes by using TBI and cyclophosphamide].

Abstract

This study was aimed to investigate a new method of avoiding graft-vs-host disease (GVHD) through selective elimination of alloreactive donor lymphocytes by using total body irradiation (TBI) and cyclophosphamide (Cy). Female (BALB/c x C57BL/6) F1 mice (H-2(d/b)) as recipients received (60)Co gamma-ray sublethal TBI of 4 Gy on day 0 followed by being inoculated with P388D1 leukemia cell line on day 1, injection of allogeneic splenocytes from C57BL/6 male mice (H-2(b)) was carried out for induction of graft-vs-leukemia (GVL) effect prior to stem cell transplantation (SCT), intraperitoneally injection of cyclophosphamide (Cy) (200 mg/kg) and TBI (9 Gy) was given on day 6. One day later, treated mice were rescued with bone marrow hematopoietic stem cells from (BALB/c x C57BL/6) F1 male mice (H-2(d/b)). The results showed that recipients had no occurrence of leukemia and GVHD through selective elimination of alloreactive donor lymphocytes by Cy and TBI, survived more than 210 days, the complete-donor chimerism occurred on day 21 after transplantation. The ratio of chimerism descended subsequently, but still displayed mixed-chimerism at 90 days. Control mice died of GVHD, leukemia or other death-related-transplantation within 20 to 36 days (P<0.01). It is concluded that to induce GVL effects by MHC mismatched splenocytes given before syngeneic bone marrow transplantation followed by selective elimination of alloreactive donor lymphocytes through TBI and Cy, graft-vs-host disease was thus avoided.

• Authors: Bao-An Chen, Wei-Min Dong, Jia-Hua Ding, Xue-Mei Sun, Xiao-Jing Deng, Yan Zhang, Yan-Zhi Bi, Gang Zhao, Chong Gao, Yun-Yu Sun, Jun Wang, Jian Cheng, M Schmitt, A Schmitt
• Journal: Zhongguo shi yan xue ye xue za zhi (Zhongguo Shi Yan Xue Ye Xue Za Zhi) Vol. 15 Issue 2 Pg. 332-6 (Apr 2007) ISSN: 1009-2137 [Print] China
• PMID: 17493342 (Publication Type: English Abstract, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cyclophosphamide

Topics

• Animals
• Cyclophosphamide (therapeutic use)
• Female
• Graft vs Host Disease (prevention & control)
• Graft vs Tumor Effect
• Hematopoietic Stem Cell Transplantation (adverse effects)
• Leukemia P388 (therapy)
• Lymphocyte Depletion
• Lymphocytes (immunology)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Whole-Body Irradiation