Graft-versus-tumor induction with donor leukocyte infusions as primary therapy for patients with malignancies

purpose: Histocompatible allogeneic donor leukocyte infusions (DLIs) were a dministered as primary cancer therapy in a phase I trial to determine (1) w hether mixed chimerism could be detected without a prior allogeneic transpl antation, (2) the toxicity of primary DLI, and (3) whether a graft-versus-t umor (GVT) reaction could be observed. Patients and Methods: Eighteen patients were studied, Patients received int erferon alfa-ab for a minimum of 4 weeks, followed by DLI (level 1). Patien ts with no toxicity or engraftment were eligible to receive cytarabine or c yclophosphamide followed by another course of DLI (level 2). Engraftment wa s determined using polymerase chain reaction amplification of donor and hos t-specific DNA polymorphisms. Results: Donor cells were detected in the blood in 14 of 16 assessable pati ents within 1 hour of DLI. Chimerism detectable 4 weeks after DLI was obser ved in four patients, and five patients were not assessable. Prior autologo us transplantation was associated with late chimerism (P =.0014). Acute gra ft-versus-host disease (GVHD) occurred in four of 16 assessable patients (g rade 1, two patients; grade 2, one patient; grade 4, one patient). One pati ent with grade 4 acute GVHD developed pancytopenia. Only the four patients treated after prior autologous transplantation developed acute GVHD (P =.00 05). Three of four patients with acute GVHD and late chimerism responded to primary DLI, and one patient was not assessable for response. Conclusion: Allogeneic adoptive immunotherapy resulted in sustained chimeri sm, acute GVHD, and a GVT response in heavily pretreated patients, This ind icates that it may be possible to generate a direct GVT response for patien ts with malignancies without the need for intensive conditioning therapy im mediately before DLI. Immunosuppression may be required for sustained donor cell engraftment. (C) 1999 by American Society of Clinical Oncology.