Reduced‐intensity conditioning for allogeneic haematopoietic stem cell transplantation in relapsed and refractory Hodgkin lymphoma: impact of alemtuzumab and donor lymphocyte infusions on long‐term outcomes

Abstract

The introduction of reduced‐intensity conditioning (RIC) has enabled the role of allogeneic transplantation to be re‐evaluated in Hodgkin lymphoma (HL). While T‐cell depletion reduces graft‐versus‐host disease (GvHD), it potentially abrogates graft‐versus‐tumour activity and increases infective complications. We compared the results in 67 sibling donor transplantations following RIC in multiply relapsed patients from two national phase II studies conditioned with fludarabine/melphalan. One used cyclosporine/alemtuzumab (MF‐A, n = 31), the other used cyclosporine/methotrexate (MF, n = 36) as GvHD prophylaxis. There was a small excess of chemorefractory cases in the MF cohort (P = NS). MF‐A resulted in significantly lower incidences of non‐relapse mortality, acute and chronic GvHD, but no significant excess of relapse/progression. Post donor lymphocyte infusion (DLI) disease responses occurred in 8/14 (57%) and 6/11 (55%) patients in the MF‐A and MF groups, respectively. Current progression‐free survival (CPFS) was superior with MF‐A (univariate analysis), with durable responses to DLI contributing to the favourable outcome (43% vs. 25%, P = 0·0356). Disease status at transplantation significantly influenced overall survival (P = 0·0038) and CPFS (P = 0·0014), retaining significance in multivariate analyses, which demonstrated a trend towards improved CPFS with T‐cell depletion (P = 0·0939). These data suggest that alemtuzumab significantly reduced GvHD without resulting in a deleterious impact on survival outcomes following RIC in HL, and that durable responses to DLI may be more common following the inclusion of alemtuzumab in the conditioning protocol.