Background and Aims; Relapse of primary hematologic malignancy after allogeneic hematopoietic stem cell transplantation (HSCT) reflects a failure of immune-mediated graft-versus-leukemia (GVL) and is invariably terminal with an overall survival (OS) at 2 years of <10%. We have demonstrated that type I Interferons (e.g. IFNα) regulate both GVL and graft versus host disease (GVHD) by sensitizing residual malignancy to cytotoxicity and augmenting donor T and NK cell cytotoxic GVL responses (Robb R et al, Blood 2011, 118:3399 and Robb R et al, Blood 2012, 119:5918).  Based on these preclinical data, we undertook a phase I/II study of pegylated-Inteferon-2α, with or without donor lymphocyte infusion (DLI) in this patient group.

Methods; Patients between 18 and 70 years were treated with Fludarabine and Cytarabine chemotherapy (FLAG) followed by escalating weekly doses of peg-IFN2α for up to 6 months. Those without grade II-IV acute GVHD or progressive chronic GVHD were eligible to receive DLI. The primary endpoint is 2 year OS.

Results and Discussion; Current 2 year OS is 29.598% (median follow-up 803 days).  This represents a clinically significant improvement compared to our historical institutional control cohort (2 yr OS 7%).  77.3% of patients experienced GHVD after administration of peg-IFN2α alone.  Long term survival is observed amongst patients who did develop GVHD.  GVHD developed in only 4 of 10 patients receiving DLI and no long term survivors were seen in this group.  48% of patients have had adverse events; however only 4 were probably or definitely related to per protocol treatment.  Development of GVHD was associated with preservation of a population of Granzyme positive, Interferon γ secreting CD8 T cells.  These data support the safety and efficacy of peg-IFN2α as an effective immunotherapy for patients with relapse after HPCT.