Graft-versus-leukemia effects from donor lymphocyte infusion after nonmyeloablative allogeneic bone marrow transplantation in mice.
BACKGROUND
Nonmyeloablative allogeneic bone marrow transplantation has been used since the 1990s as a new hematological stem cell transplantation strategy for treating hematological diseases. The purpose of this study was to explore the graft-versus-leukemia (GVL) effects of donor lymphocyte infusions (DLIs) after nonmyeloablative allogeneic bone marrow transplantations, while assessing the declines in treatment-associated morbidity, mortality, and graft-versus-host disease (GVHD).


METHODS
A total of 615 (H-2k) mice were injected with L615 tumor cells and received 500 cGy (60Co gamma-ray) irradiation three days later, followed by an allogeneic bone marrow transplantation (allo-BMT). The allo-grafts consisted of 3 x 10(7) bone marrow cells and 1 x 10(7) spleen cells from BALB/C (H-2d) donor mice. Two days after the allo-BMT, the recipient mice were given 200 mg/kg of cyclophosphamide. Subsequently, recipient mice were infused with either donor spleen cells (2 x 10(7)) on day 14 or 21, or donor spleen cells (5 x 10(7)) pretreated with hydrocortisone and cyclosporin A (CsA) in vitro on day 14 post-BMT.


RESULTS
The median survival time of mice that received DLI on day 21 and pretreated DLI on day 14 post-BMT was longer than that of controls and the day 14 DLI group (P < 0.01). No evidence of severe GVHD was observed in the day 21 DLI group nor in the day 14 treated DLI group. Mixed chimerism was confirmed in the day 14 DLI group, the day 14 treated DLI group, and the day 21 DLI group on the thirteenth day post-transplantation; full donor chimerism was observed two weeks after DLI.


CONCLUSIONS
Donor lymphocyte infusion after nonmyeloablative bone marrow transplantation may reduce transplantation-associated morbidity and mortality while strengthening graft-versus-leukemia effects.
Du
Bing
B
Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China.
Li
De-peng
DP
Xu
Kai-lin
KL
Pan
Xiu-ying
XY
D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology*; D016572:Cyclosporine / Q000494:pharmacology; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology; D020544:Graft vs Leukemia Effect / Q000276:immunology*; D006854:Hydrocortisone / Q000494:pharmacology; D008213:Lymphocyte Activation; D017710:Lymphocyte Transfusion; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018183:Transplantation Chimera; D014184:Transplantation, Homologous
D016572:Cyclosporine; D006854:Hydrocortisone