Graft-Versus-Leukemia Reactions After Bone Marrow Transplantation

• Published in: Blood 1990-02, Vol.75 (3), p.555-562
• Main Authors: Horowitz, Mary M., Gale, Robert Peter, Sondel, Paul M., Goldman, John M., Kersey, John, Kolb, Hans-Jochem, Rimm, Alfred A., Ringdén, Olle, Rozman, Ciril, Speck, Bruno, Truitt, Robert L., Zwaan, Ferdinand E., Bortin, Mortimer M.
• Format: Article
• Language: English
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Biological and medical sciences; Bone Marrow Transplantation - immunology; Bone marrow, stem cells transplantation. Graft versus host reaction; Graft vs Host Disease - immunology; Humans; Leukemia, Myeloid, Acute - immunology; Leukemia, Myeloid, Acute - surgery; Medical sciences; Multivariate Analysis; Precursor Cell Lymphoblastic Leukemia-Lymphoma - immunology; Precursor Cell Lymphoblastic Leukemia-Lymphoma - surgery; Risk Factors; T-Lymphocytes - immunology; Transfusions. Complications. Transfusion reactions. Cell and gene therapy
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V75.3.555.555

To determine whether graft-versus-leukemia (GVL) reactions are important in preventing leukemia recurrence after bone marrow transplantation, we studied 2,254 persons receiving HLA-identical sibling bone marrow transplants for acute myelogenous leukemia (AML) in first remission, acute lymphoblastic leukemia (ALL) in first remission, and chronic myelogenous leukemia (CML) in first chronic phase. Four groups were investigated in detail: recipients of non-T-cell depleted allografts without graft-versus-host disease (GVHD), recipients of non-T-cell depleted allografts with GVHD, recipients of T-cell depleted allografts, and recipients of genetically identical twin transplants. Decreased relapse was observed in recipients of non-T-cell depleted allografts with acute (relative risk 0.68, P = .03), chronic (relative risk 0.43, P = .01 ), and both acute and chronic GVHD (relative risk 0.33, P = .0001 ) as compared with recipients of non-T-cell depleted allografts without GVHD. These data support an antileukemia effect of GVHD. AML patients who received identical twin transplants had an increased probability of relapse (relative risk 2.58, P = .008) compared with allograft recipients without GVHD. These data support an antileukemia effect of allogeneic grafts independent of GVHD. CML patients who received T-cell depleted transplants with or without GVHD had higher probabilities of relapse (relative risks 4.45 and 6.91, respectively, P = .0001 ) than recipients of non-T-cell depleted allografts without GVHD. These data support an antileukemia effect independent of GVHD that is altered by T-cell depletion. These results explain the efficacy of allogeneic bone marrow transplantation in eradicating leukemia, provide evidence for a role of the immune system in controlling human cancers, and suggest future directions to improve leukemia therapy.