Protective Conditioning for Acute Graft-versus-Host Disease
Robert Lowsky, M.D., Tsuyoshi Takahashi, M.D., Ph.D., Yin Ping Liu, M.D., Sussan Dejbakhsh-Jones, M.S., F. Carl Grumet, M.D., Judith A. Shizuru, M.D., Ph.D., Ginna G. Laport, M.D., Keith E. Stockerl-Goldstein, M.D., Laura J. Johnston, M.D., Richard T. Hoppe, M.D., Daniel A. Bloch, Ph.D., Karl G. Blume, M.D., Robert S. Negrin, M.D., and Samuel Strober, M.D.
Background Conditioning with total lymphoid irradiation plusantithymocyte serum protects mice against acute graft-versus-hostdisease (GVHD) after hematopoietic-cell transplantation. Wetested this strategy in humans.
Methods Thirty-seven patients with lymphoid malignant diseasesor acute leukemia underwent an experimental conditioning regimenwith 10 doses of total lymphoid irradiation (80 cGy each) plusantithymocyte globulin, followed by an infusion of HLA-matchedperipheral-blood mononuclear cells from related or unrelateddonors who received granulocyte colony-stimulating factor.
Results Of the 37 transplant recipients, only 2 had acute GVHDafter hematopoietic-cell transplantation. Potent antitumor effectsin patients with lymphoid malignant diseases were shown by thechange from partial to complete remission. In the transplantrecipients who underwent conditioning with total lymphoid irradiationand antithymocyte globulin, the fraction of donor CD4+ T cellsthat produced interleukin-4 after in vitro stimulation increasedby a factor of five, and the proliferative response to alloantigensin vitro was reduced, as compared with normal control subjectsand control subjects who underwent conditioning with a singledose of total-body irradiation (200 cGy).
Conclusions A regimen of total lymphoid irradiation plus antithymocyteglobulin decreases the incidence of acute GVHD and allows graftantitumor activity in patients with lymphoid malignant diseasesor acute leukemia treated with hematopoietic-cell transplantation.
Source Information
From the Departments of Medicine (R.L., T.T., Y.P.L., S.D.-J., J.A.S., G.G.L., K.E.S.-G., L.J.J., K.G.B., R.S.N., S.S.), Pathology (F.C.G.), Radiation Oncology (R.T.H.), and Health Research and Policy (D.A.B.), Stanford University School of Medicine, Stanford, Calif.
Address reprint requests to Dr. Strober at the Center for Clinical Sciences Research Building, Rm. 2215, 269 W. Campus Dr., Stanford, CA 94305-5290.
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A correction has been published: N Engl J Med 2006;354(8):884.
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