Graft-versus-tumor induction with donor leukocyte infusions as primary therapy for patients with malignancies.
OBJECTIVE
Histocompatible allogeneic donor leukocyte infusions (DLIs) were administered as primary cancer therapy in a phase I trial to determine (1) whether mixed chimerism could be detected without a prior allogeneic transplantation, (2) the toxicity of primary DLI, and (3) whether a graft-versus-tumor (GVT) reaction could be observed.


METHODS
Eighteen patients were studied. Patients received interferon alfa-2b for a minimum of 4 weeks, followed by DLI (level 1). Patients with no toxicity or engraftment were eligible to receive cytarabine or cyclophosphamide followed by another course of DLI (level 2). Engraftment was determined using polymerase chain reaction amplification of donor and host-specific DNA polymorphisms.


RESULTS
Donor cells were detected in the blood in 14 of 16 assessable patients within 1 hour of DLI. Chimerism detectable 4 weeks after DLI was observed in four patients, and five patients were not assessable. Prior autologous transplantation was associated with late chimerism (P =.0014). Acute graft-versus-host disease (GVHD) occurred in four of 16 assessable patients (grade 1, two patients; grade 2, one patient; grade 4, one patient). One patient with grade 4 acute GVHD developed pancytopenia. Only the four patients treated after prior autologous transplantation developed acute GVHD (P =.0005). Three of four patients with acute GVHD and late chimerism responded to primary DLI, and one patient was not assessable for response.


CONCLUSIONS
Allogeneic adoptive immunotherapy resulted in sustained chimerism, acute GVHD, and a GVT response in heavily pretreated patients. This indicates that it may be possible to generate a direct GVT response for patients with malignancies without the need for intensive conditioning therapy immediately before DLI. Immunosuppression may be required for sustained donor cell engraftment.
Porter
D L
DL
Division of Hematology-Oncology, Department of Medicine, University of Pennsylvania Medical Center, Philadelphia 19104, USA. dlporter@mailm.med.upenn.edu
Connors
J M
JM
Van Deerlin
V M
VM
Duffy
K M
KM
McGarigle
C
C
Saidman
S L
SL
Leonard
D G
DG
Antin
J H
JH
D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002678:Chimera; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology; D020350:Graft vs Tumor Effect / Q000276:immunology*; D006801:Humans; D016219:Immunotherapy, Adoptive; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D017708:Leukocyte Transfusion; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins; D012074:Remission Induction; D014019:Tissue Donors; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins