Selective elimination of alloreactive donor lymphocytes by using TBI and cyclophosphamide.
- Author:
Bao-An CHEN
1
;
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
Author Information
1. Department of Hematology, Zhongda Hospital of Southeast University, Nanjing 210009, China.
- Publication Type:Journal Article
- MeSH:
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
- From:
Journal of Experimental Hematology
2007;15(2):332-336
- CountryChina
- Language:Chinese
-
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.