title: [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.affiliation: Department of Hematology, Zhongda Hospital of Southeast University, Nanjing 210009, China.
authors.forename: Bao-An
authors.initials: BA
authors.lastname: Chen
authors.forename: Wei-Min
authors.initials: WM
authors.lastname: Dong
authors.forename: Jia-Hua
authors.initials: JH
authors.lastname: Ding
authors.forename: Xue-Mei
authors.initials: XM
authors.lastname: Sun
authors.forename: Xiao-Jing
authors.initials: XJ
authors.lastname: Deng
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yan-Zhi
authors.initials: YZ
authors.lastname: Bi
authors.forename: Gang
authors.initials: G
authors.lastname: Zhao
authors.forename: Chong
authors.initials: C
authors.lastname: Gao
authors.forename: Yun-Yu
authors.initials: YY
authors.lastname: Sun
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Jian
authors.initials: J
authors.lastname: Cheng
authors.forename: M
authors.initials: M
authors.lastname: Schmitt
authors.forename: A
authors.initials: A
authors.lastname: Schmitt
mesh_terms: 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
chemical_list: D003520:Cyclophosphamide