title: Total lymphoid irradiation to prevent graft rejection in recipients of HLA non-identical T cell-depleted allogeneic marrow.
abstract: Patients who undergo transplantation with genotypically non-identical T cell-depleted bone marrow are at high risk of graft failure. We have previously shown that graft failure in this setting is an active immunologic process in which CD3+ CD8+ host T cells specifically cytotoxic for donor hematopoietic cells mediate rejection of the graft. In order to reduce the incidence of graft rejection in these patients, we conducted a pilot trial of total lymphoid irradiation (TLI) as an adjunct to total body irradiation (TBI) in an attempt to suppress the activity of residual host derived alloreactive lymphocytes capable of mediating rejection. Ten adults (ages 17-42 years) with hematologic malignancies were treated with TLI prior to hospitalization for allogeneic bone marrow transplantation (BMT). The BMT preparative regimen consisted of cyclophosphamide (60 mg/kg x 2) followed by TBI. The majority of patients received 750 cGy TLI delivered to two complementary radiation ports in five equal 150 cGy fractions. Nine of 10 recipients of genotypically non-identical CD6-depleted marrow who were pre-treated with TLI experienced full hematologic engraftment compared with none of four similar patients previously transplanted without TLI (p = 0.001). TLI induced significant lymphopenia in patients prior to marrow infusion, but had no suppressive effects on the reconstitution of donor lymphocytes. TLI, in combination with T cell depletion of donor marrow, may decrease the rate of graft rejection in individuals who lack perfectly matched HLA-identical sibling donors.
authors.affiliation: Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, MA 02115.
authors.forename: R J
authors.initials: RJ
authors.lastname: Soiffer
authors.forename: P
authors.initials: P
authors.lastname: Mauch
authors.forename: N J
authors.initials: NJ
authors.lastname: Tarbell
authors.forename: K C
authors.initials: KC
authors.lastname: Anderson
authors.forename: A S
authors.initials: AS
authors.lastname: Freedman
authors.forename: S N
authors.initials: SN
authors.lastname: Rabinowe
authors.forename: T
authors.initials: T
authors.lastname: Takvorian
authors.forename: C I
authors.initials: CI
authors.lastname: Murrey
authors.forename: F
authors.initials: F
authors.lastname: Coral
authors.forename: L
authors.initials: L
authors.lastname: Bosserman
mesh_terms: D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation / Q000276:immunology* / Q000473:pathology; D003520:Cyclophosphamide / Q000627:therapeutic use; D005260:Female; D006084:Graft Rejection / Q000528:radiation effects*; D006086:Graft vs Host Disease / Q000517:prevention & control*; D006680:HLA Antigens / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D008212:Lymphocyte Depletion; D008221:Lymphoid Tissue / Q000528:radiation effects*; D008297:Male; D010865:Pilot Projects; D013601:T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D014916:Whole-Body Irradiation
chemical_list: D006680:HLA Antigens; D003520:Cyclophosphamide