[Selective elimination of alloreactive donor lymphocytes by using TBI and cyclophosphamide].
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.
Chen
Bao-An
BA
Department of Hematology, Zhongda Hospital of Southeast University, Nanjing 210009, China.
Dong
Wei-Min
WM
Ding
Jia-Hua
JH
Sun
Xue-Mei
XM
Deng
Xiao-Jing
XJ
Zhang
Yan
Y
Bi
Yan-Zhi
YZ
Zhao
Gang
G
Gao
Chong
C
Sun
Yun-Yu
YY
Wang
Jun
J
Cheng
Jian
J
Schmitt
M
M
Schmitt
A
A
D000818:Animals; D003520:Cyclophosphamide / Q000627:therapeutic use; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control*; D020350:Graft vs Tumor Effect; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D007941:Leukemia P388 / Q000628:therapy*; D008212:Lymphocyte Depletion; D008214:Lymphocytes / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D014916:Whole-Body Irradiation
D003520:Cyclophosphamide