Donor Leukocyte Infusions (DLIs) for Recurrent Hodgkin Lymphoma (HL) Following Allogeneic Stem Cell Transplantation (allo-SCT): Ten-Year Experience at the M.D. Anderson Cancer Center

The role of DLIs in the management of recurrent HL following allo-SCT is not well established. Response rates in the 30–50% range have been reported (as high as 79% in a recent report), but their durability and impact on patient survival are not always clear (Peggs et al, BJH 2008; 143:468 and JCO 2011; 29: 971). We wish to update our initial report on this issue (Anderlini et al, BMT 2004; 34: 511). For more details on response criteria definitions, please refer to our original report.

Between 1999 and 2010, 27 consecutive patients with relapsed/refractory HL following unmanipulated allo-SCT received a total of 55 DLIs as immunotherapy for treatment of progressive disease (PD). Their median age was 30 years (19–60; M/F 19/8), and 21/27 (78%) had a history of prior autologous SCT. Seventeen patients received more than one DLI (range 2–5). Seventeen had a matched sibling/parent donor and ten a matched unrelated donor. In all but two cases the conditioning regimen included fludarabine plus cyclophosphamide or melphalan plus/minus antithymocyte globulin. The median time to PD after allo-SCT was 5 months (range 1–21). In ten patients (37%) prior salvage chemotherapy was administered prior to at least one of their DLIs. The pre-DLI chimerism status was 2/27 mixed and 25/27 full donor.

Ten of 27 (37%) patients had a complete/partial response (CR/PR) following at least one of their DLIs. Six of 27 patients (22%) achieved CR/CRU (complete response, unknown), and four of 27(15%) achieved a PR. The median response duration was 7.5 months (range 0.5–20). Of all these ten responders, 100% developed graft-vs-host disease (GVHD) and half of them (50%) had received concomitant chemotherapy. Of the ten patients who received only one DLI, two (20%) had chemotherapy prior to their DLIs. One (10%) had a CRU and the other had stable disease (SD) (10%). Of the remaining eight that did not have chemo prior to DLI, 2 (20%) had CRU, 3 (30%) had PR, 2 (20%) had SD and 1 (10%) had PD. The median CD3+ cell dose administered was 49.8 × 10E6/ kg (range 0.05–285). GVHD developed (or flared) following the DLI in 45/55 cases (82%). After the DLI mixed chimerism (n=2) was converted to complete (or near-complete) donor chimerism. At the latest follow-up (March 2011), five patients (18%) are alive (two in CR). For these five survivors, the follow-up after the 1^st DLI is 42 months (range 4–63). Four of them (80%) did not receive chemotherapy with their DLI(s), while one did. Twenty-two patients expired. Their median survival after the 1^st DLI was 14 months (range 4–64). Causes of death included PD (n=15; 68%) and non-relapse mortality (n=7; 32%).

Despite the limitations related to the small sample size, patient heterogeneity and concomitant chemotherapy administration, these data suggest that (a) DLIs for immunotherapy of recurrent HL following allo-SCT have significant (albeit not always durable) activity, and a subset of patients become long-term survivors (b) administration of multiple DLIs is feasible in selected patients (c) responses are associated with the development of GVHD (d) the role (if any) of concomitant chemotherapy is unclear and, lastly (e) PD remains the main cause of mortality following DLIs. The role of DLIs should be reassessed in the contest of new and effective agents now available in the salvage setting (SGN-35, panobinostat, etc).

Off Label Use: Fludarabine, cyclophosphamide and melphalan as part of conditioning regimen for allogeneic stem cell transplantation.