+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Donor lymphocyte infusion-mediated graft-versus-leukemia effects in mixed chimeras established with a nonmyeloablative conditioning regimen: extinction of graft-versus-leukemia effects after conversion to full donor chimerism



Donor lymphocyte infusion-mediated graft-versus-leukemia effects in mixed chimeras established with a nonmyeloablative conditioning regimen: extinction of graft-versus-leukemia effects after conversion to full donor chimerism



Transplantation 76(2): 297-305



Background: We investigated an approach to separating graft-versus-lymphoma (GVL) effects from graft-versus-host disease (GVHD) in mice receiving a nonmyeloablative conditioning regimen allowing establishment of mixed hematopoietic chimerism. Methods: We evaluated the ability of donor lymphocyte infusions (DLI) to mediate GVL effects without GVHD in mixed chimeras prepared with cyclophosphamide, anti-T-cell antibodies, and thymic irradiation. To examine the fate of GVH-reactive donor CD8+ T cells, we used the 2C T-cell receptor (TCR) transgenic mouse strain, which carries an Ld-specific transgenic TCR on the B6 background. Results: Administration of DLI on day 35 post-BMT led to conversion from mixed to full donor chimerism and mediated a powerful GVL effect with complete protection (100% survival) against mortality induced by a host-type lymphoma (EL4) administered 7 days later (100% mortality in non-DLI controls; P<0.001). No GVHD occurred in DLI recipients. Rechallenging the surviving DLI recipients, which had converted to full chimerism, with the same tumor dose 17 weeks later led to rapid tumor mortality. Long-term DLI recipients had anti-host proliferative responses, but not CTL responses in vitro. When given as DLI together with wild-type spleen cells, marked expansion of GVH-reactive 2C CD8+ T cells was observed on day 10, followed by a marked decline in their numbers by week 10 post-DLI. Conclusions: Nonmyeloablative induction of mixed chimerism followed by administration of DLI can mediate powerful GVL effects. The late loss of DLI-mediated GVL effects may reflect the eventual loss of do nor-derived GVH-reactive CTL, which occurs in association with conversion to full donor chimerism.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 010493310

Download citation: RISBibTeXText

PMID: 12883182

DOI: 10.1097/01.tp.0000072014.83469.2d


Related references

Graft-versus-leukemia effect of donor lymphocyte infusion without GVHD in mixed chimeras prepared with non-myeloablative conditioning Can recipient leukocyte infusion also induce GVL effects?. Blood 96(11 Part 1): 177a, 2000

Administration of donor lymphocyte infusions leads to superior graft-versus-leukemia-reactions in mixed hematopoietic chimeras than in full donor chimeras. Blood 96(11 Part 1): 176a, 2000

Graft-versus-leukemia effects, mixed chimerism and early T-cell reconstitution in two patients with advanced stage chronic lymphocytic leukemia after bone marrow transplantation with a novel nonmyeloablative conditioning regimen. Blood 94(10 Suppl. 1 Part 1): 349a, 1999

Donor lymphocyte infusion for mixed chimerism or residual disease after reduced-intensity T Cell depleted stem cell transplantation results in conversion to full donor chimerism combined with graft versus tumor responses and limited GVHD. 2007

Graft-versus-leukemia effects from donor lymphocyte infusion after nonmyeloablative allogeneic bone marrow transplantation in mice. Chinese Medical Journal 118(6): 474-479, 2005

Study on graft-versus-leukemia effects of donor lymphocyte infusion after nonmyeloablative allogeneic bone marrow transplantation. Zhonghua Xue Ye Xue Za Zhi 22(8): 403-407, 2001

Graft-versus-host-reactive donor CD4 cells can induce T cell-mediated rejection of the donor marrow in mixed allogeneic chimeras prepared with nonmyeloablative conditioning. Blood 103(2): 732-739, 2004

Effects of sensitized donor lymphocyte infusion on the chimerism and graft-versus-host disease after nonmyeloablative allogeneic stem cell transplantation. Zhongguo Shi Yan Xue Ye Xue Za Zhi 14(1): 102-106, 2006

Donor T cells primed on leukemia lysate-pulsed recipient APCs mediate strong graft-versus-leukemia effects across MHC barriers in full chimeras. Blood 113(18): 4440-4448, 2009

Mixed chimerism and graft failure following conditioning with the fludarabine and cyclophosphamide nonablative regimen; conversion to full donor chimerism. American Journal of Hematology 82(6): 419-426, 2007

Impact of pretransplant conditioning and donor T cells on chimerism, graft-versus-host disease, graft-versus-leukemia reactivity, and tolerance after bone marrow transplantation. Blood 77(11): 2515-2523, 1991

Donor lymphocyte infusions mediate superior graft-versus-leukemia effects in mixed compared to fully allogeneic chimeras: a critical role for host antigen-presenting cells. Blood 100(5): 1903-1909, 2002

Graft-versus-leukemia and graft-versus-host reactions after donor lymphocyte infusion are initiated by host-type antigen-presenting cells and regulated by regulatory T cells in early and long-term chimeras. Biology of Blood and Marrow Transplantation 12(4): 397-407, 2006

Influence of Conditioning Regimens with Total Body Irradiation (Tbi) on Graft Versus Host Disease and Graft Versus Leukemia Effect Following Donor Lymphocyte Infusions (Dli). Biology of Blood and Marrow Transplantation 25(3): S176-S177, 2019

Graft-versus-host disease, the graft-versus-leukemia effect, and mixed chimerism following nonmyeloablative stem cell transplantation. International Journal of Hematology 78(3): 195-207, 2003