Donor lymphocyte infusions can result in sustained remissions in patients with residual or relapsed lymphoid malignancy following allogeneic haemopoietic stem cell transplantation

Abstract

Summary:We treated 17 patients with refractory (n ¼ 7) or relapsed lymphoid malignancy (n ¼ 10) following allogeneic HSCT with donor lymphocyte infusions (DLI). Patients with lowgrade disease received DLI alone (n ¼ 7) or following radiotherapy (n ¼ 1). Patients with aggressive disease (n ¼ 9) received prior chemotherapy. Nine out of 15 patients receiving DLI from sibling donors responded after one (n ¼ 6), two (n ¼ 2) and three (n ¼ 1) infusions. Both MUD recipients achieved CR after two and three DLI. In all, 10/17 patients achieved CR including 3/4 patients with chronic lymphatic leukaemia (CLL), 4/4 with mantle cell lymphoma (MCL), 3/4 with follicular NHL but 0/5 with aggressive NHL/Richters. The median CD3 cell dose to achieve CR for siblings was 2 Â 10 7 /kg. One patient with CLL had a second transplant following DLI-induced aplasia and is in CR at 14 months giving a final CR rate of 64%. Grade II-IV acute GVHD developed in 45% and chronic GVHD in 8/9 evaluable patients. Of the 11 patients finally achieving CR, one patient with MCL relapsed at 18 months post-DLI but all others remain in remission with a median follow-up of 40 months (range 12-64 months). Low-grade NHL and MCL have a high response rate and sustained remissions following DLI. Aggressive disease responds poorly however, despite pre-DLI chemotherapy.

The outcome of reduced intensity allogeneic stem cell transplantation and autologous stem cell transplantation when performed as a first transplant strategy in relapsed follicular lymphoma: an analysis from the Lymphoma Working Party of the EBMT

“…The existence of a GVL effect in FL has been demonstrated by the ability of DLIs to induce remissions in disease relapsing post allograft. [25][26][27] This study is not able to determine which of these mechanisms underlies the lower relapse rate, although both mechanisms are likely to be active. In this study, we were not able to demonstrate an impact of T-cell depletion on the relapse rate following an allo-SCT as suggested by others.…”

The role of high-dose therapy and stem cell rescue in the management of T-cell malignant lymphomas: a BSBMT and ABMTRR study

“…23 One potential way to reduce the high transplant-related mortality rate would be to employ an RIC, which would facilitate engraftment as a platform upon which to develop the GvLy effect, including the programmed use of donor lymphocyte infusions. 19,24 Corradini et al 12 reported prospectively on 17 patients with relapsed/primary refractory T-cell lymphomas treated with RIC Allo-SCT. Estimated 3-year OS and PFS were promising at 81 and 64%, respectively, with low NRM estimated 6% at 2 years.…”

Long-term progression-free survival after early autologous transplantation for mantle-cell lymphoma

“…26 Furthermore, reduced-intensity conditioning regimens allow allogeneic transplantation of a broader group of patients, and available data suggest that durable responses may be achieved in a substantial proportion of patients with relapsed or refractory MCL, suggesting that MCL is subject to potent GVL effects. 14,[27][28][29][30] Historically, MCL has been characterized by relatively brief remissions and short survival times relative to other non-Hodgkin's lymphoma subtypes. The developments of more aggressive induction chemotherapy regimens and monoclonal antibody therapy and advances in both transplantation and supportive care have improved the outlook for patients with MCL.…”