Failure of Donor Lymphocyte Infusion to Prevent Graft Rejection in Dogs Given DLA-Identical Marrow after 1 Gy of Total Body Irradiation

Abstract

We investigated in a preclinical canine model of hematopoietic cell transplantation (HCT) whether preemptive donor lymphocyte infusion (DLI) given 1 month after HCT could prevent late graft rejection that was the rule in historical dogs given suboptimal conditioning with 1 Gy of total body irradiation (TBI) before and immunosuppression with cyclosporine (CSP) and either mycophenolate mofetil (MMF; n = 6) or rapamycin (n = 5) after dog leukocyte antigen (DLA)-identical marrow transplantation. Nine dogs given DLA-identical marrow after 1 Gy of TBI followed by postgrafting MMF and CSP were studied. A single DLI was given 28-36 days after HCT, either with (n = 5) or without (n = 4) preceding treatment with the immunosuppressive drug pentostatin. Two of the 4 dogs given DLI only maintained stable mixed donor–host chimera beyond 30 weeks after HCT, whereas 2 rejected their grafts, on weeks 10 and 15 after HCT. One of the 5 dogs given pentostatin before DLI maintained a stable mixed donor–host chimera beyond 30 weeks, whereas 4 rejected their grafts, at weeks 8, 12, 12, and 16 after HCT. The 30-week probability of stable mixed chimerism was 33% among dogs given DLI, versus 0% among 11 historical dogs ( P = .003). In conclusion, DLI was only moderately effective in preventing graft rejection in this model. Additional immunosuppression with pentostatin did not improve that outcome. The model might be useful in developing potential strategies aimed at preventing graft rejection in patients with low donor chimerism levels.