Immunotherapy with Donor Leukocyte Infusions (DLIS) in Relapsed Hodgkin’s Disease (HD) Following Allogeneic Stem Cell Transplantation (ALLO-SCT): CD3+ Cell Dose, GVHD and Disease Response.

Background: There is paucity of data on DLIs for the management of recurrent HD following allo-SCT, and on whether CD3+ cell dose is relevant to response (and the development of GVHD) as is the case in chronic myeloid leukemia.

Patients: Nine patients with advanced HD who had undergone allo-SCT received DLIs as immunotherapy for treatment of progressive disease (PD). A total of fifteen DLIs were performed, with four patients receiving more than one DLI. Their median age was 30 years (18–42), and 7/9 had failed a prior autologous SCT. In four patients prior chemotherapy was administered.. Seven had a matched sibling donor and two a matched unrelated donor, and in all but one case the conditioning regimen included fludarabine plus cyclophosphamide or melphalan (plus/minus antithymocyte globulin). The pre-DLI chimerism status was 2/9 mixed and 7/9 full donor.

Results: The CD3+ cell dose administered was 77.5 x 10E6/kg (5–285). GVHD developed following the DLI in all but one patient and after 9/15 DLIs (60%). The response rate (complete/partial response) was 4/9 (44%). Three of these four responders developed GVHD and 3/4 had received chemotherapy. After the DLI mixed chimerism (n=2) was converted to complete (or near-complete) donor chimerism. The median response duration was 7 months (range 4-9+). No correlation (or threshold) was observed between CD3+ cell dose infused and disease response. The correlation between CD3+ cell dose and GVHD could not be evaluated statistically as all but one patient developed GVHD. At the latest follow-up three patients are alive (one in ongoing complete remission) and six have expired (PD n=3, non-relapse mortality n=3).

Conclusions: These data suggest that DLIs for immunotherapy of recurrent HD following allo-SCT have significant activity, although they frequently lead to GVHD (and, if not already present, full donor chimerism). The small sample size does not allow any firm conclusion as to whether chemotherapy administration increases the chance of response. The CD3 cell dose infused does not seem to correlate with disease response.