Clinical relevance of recipient leukocyte infusion as antitumor therapy following nonmyeloablative allogeneic hematopoietic cell transplantation.
OBJECTIVE
Graft-versus-leukemia effects of donor lymphocytes have been considered to be central to the therapeutic benefit of nonmyeloablative allogeneic hematopoietic cell transplantation (HCT) for malignant diseases. Surprisingly, some patients who reject donor grafts following nonmyeloablative HCT have sustained remissions of advanced, chemorefractory hematologic malignancies. In murine mixed chimeras prepared with nonmyeloablative conditioning, we previously showed that recipient leukocyte infusions (RLIs) induce loss of donor chimerism and mediate antitumor responses against host-type tumors. We assessed the clinical relevance of our mouse model.


METHODS
Mixed chimeric mice were generated by a nonmyeloablative protocol and some of them received host-derived tumor cells and/or RLIs or donor lymphocyte infusion (DLI). We examined chimerism, graft-versus-host disease (GVHD), and tumor survival.


RESULTS
RLI is still effective when the leukocytes are obtained from tumor-bearing mice. Established mixed chimerism is required prior to the induced rejection to achieve maximum antitumor effects. The antitumor effects of RLI are not dependent on a specific donor strain or conditioning protocol. In contrast to DLI, RLI leads to donor cell rejection without the risk of GVHD.


CONCLUSIONS
Together, these data reinforce the clinical potential of RLI therapy as a new HCT strategy that does not carry the risk of GVHD.
Saito
Toshiki I
TI
Bone Marrow Transplantation Section, Transplantation Biology Research Center, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts 02129, USA.
Rubio
Marie T
MT
Sykes
Megan
M
D000818:Animals; D002986:Clinical Trials as Topic; D006086:Graft vs Host Disease / Q000209:etiology / Q000473:pathology; D020544:Graft vs Leukemia Effect; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods; D006801:Humans; D007938:Leukemia / Q000150:complications / Q000473:pathology / Q000628:therapy*; D017710:Lymphocyte Transfusion / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D012307:Risk Factors; D013045:Species Specificity; D018183:Transplantation Chimera; D019172:Transplantation Conditioning / Q000379:methods; D014184:Transplantation, Homologous