Induction of Anti-Tumor Activity Following Autologous Stem Cell Transplantation: Immunotherapeutic Implications G.H. Marin, M.E. Menna, M.I. Bergna, J. Malacalza, C. Martin, M.C. Mendez, G. Klein, L. Montero-Labat, M.A. Gil, S. Saba, L. Gardenal, E. Mansilla, S. Orlando, C. Canepa, and G. Piccinelli S INCE the 1970s, allogeneic bone marrow transplanta- tion (BMT) has been used successfully as a therapeutic option for many patients affected by several malignancies. However, this therapy is limited to those patients in whom an HLA phenothypically matched marrow donor is available. Graft-versus-host disease (GVHD) is one of the most important complications of BMT and becomes the major cause of mortality for this type of treatment. 1 GVHD might also affect recipient tumor cells. Thus, it is often assumed that the high efficiency of BMT for tumor eradication results not only from the high dose of chemotherapy given as a conditioning regimen before transplantation, but also from the role of the immune system in controlling the tumor cells, a process known as graft versus tumor effect (GVT). 2 Unfortunately, only about one of five of the patients will find an appropriate donor for allogeneic BMT. On the other hand, autologous bone marrow transplan- tation or peripheral blood stem cell transplantation (ASCT) is always available for almost all patients. The high relapse rate of hematologic malignancies treated with ASCT may reflect the absence of GVHD/GVT effect. Since the relapse might originate from few cells that escape from the high dose chemotherapy treatment, the goal should be to elim- inate this minimal residual disease immediately after inten- sification. Immune therapy (such as GVT induction) may contribute to prevent disease recurrence after ASCT. We have previously demonstrated that autologous GVHD induction could be possible. 3 GVT effect, usually associated with GVHD, is an autoimmune syndrome initi- ated by autoeffector T cells presumed to be exported from the thymus during cyclosporine A (CsA) treatment. Al- though several reports tried to prove how these cells are alike, this point still remains unknown. Our objective was to demonstrate which are the cells responsible for GVHD reaction and show its resulting impact on patient outcome, we designed a prospective randomized trial that was applied to patients undergoing ASCT. PATIENTS AND METHODS Patients Thirty-two patients undergoing ASCT at CUCAIBA’s UTMO unit were included in a prospective randomized study over the period August 1997 to October 1999. Diagnoses were non-Hodgkin’s lymphomas (NHL) in six cases, Hodgkin’s disease (HD) in 11, multiple myelomas (MM) in four, acute myeloid leukemia (AML) in seven, and chronic myeloid leukemia (CML) in four patients. Upon admission for ASCT, patients were randomly allocated to two groups. Allocation was carried out in a stratified way according to patient diagnoses to balance the disease included in each group. From the C.U.C.A.I.B.A., Ministry of Health, Buenos Aires, Argentina. Address reprint requests to Dr G.H. Marin, Calle 18 No 227, 1900 La Plata, Argentina. Fig 2. Survival according to arm. Fig 1. Disease-free survival according to arm. 0041-1345/01/$–see front matter © 2001 by Elsevier Science Inc. PII S0041-1345(00)02769-X 655 Avenue of the Americas, New York, NY 10010 2004 Transplantation Proceedings, 33, 2004–2007 (2001)