title: Adult recipients of matched related donor blood cell transplants given myeloablative regimens including pretransplant antithymocyte globulin have lower mortality related to graft-versus-host disease: a matched pair analysis.
abstract: Because pretransplantation anti-thymocyte globulin (ATG) seems to reduce graft-versus-host-disease (GVHD) and treatment-related mortality (TRM) after unrelated donor bone marrow transplantation (BMT), we investigated this agent in matched related donor (MRD) blood cell transplantation (BCT). Fifty-four adults receiving rabbit ATG, cyclosporine A, and methotrexate with myeloablative conditioning and undergoing first MRD BCT were matched for disease and stage with 54 patients not given ATG. Most ATG-treated patients had fludarabine with oral (7) or i.v. busulfan (46) with total body irradiation (TBI) in 10. Control patients largely received TBI with VP16 (28) or oral busulfan with cyclophosphamide (15) or fludarabine (7). The ATG was given at a total dose of 4.5 mg/kg over 3 d, finishing on day 0. Rates of acute GVHD (aGVHD) grade II-IV, aGVHD grade III-IV, and chronic GVHD (cGVHD) were 19 +/- 5% versus 32 +/- 6% (P = .1), 6 +/- 3% versus 13 +/- 5% (P = NS), and 55 +/- 8% versus 96 +/- 3% (P = .002) in the ATG and control groups, respectively. Patients given ATG had fewer sites involved by cGVHD compared with the control group (mean 2.1 +/- 0.2 versus 2.8 +/- 0.2, P = .04). Non-relapse mortality (NRM) with and without ATG, respectively, was 4 +/- 3% versus 17 +/- 5% at 100 d and 9 +/- 4% versus 34 +/- 7% at 4 yr (P = .002). Deaths were GVHD related in 3 ATG-treated patients versus 14 controls (P = .007). Despite a trend to more relapse with ATG (43 +/- 7% versus 22 +/- 7% at 4 yr, P = 0.05), survival was 66 +/- 7% in the patients given ATG versus 50 +/- 7% in the controls (P = 0.046). This study indicates that myeloablative regimens incorporating fludarabine and oral or i.v. busulfan with pretransplantation ATG given to recipients undergoing MRD BCT may result in less cGVHD, lower TRM, and probably improved quality of life in survivors compared with previous protocols.
authors.affiliation: Alberta Blood and Bone Marrow Transplant Program and Departments of Medicine and Oncology, Foothills Hospital, Calgary, Alberta, Canada. jamesrus@cancerboard.ab.ca <jamesrus@cancerboard.ab.ca>
authors.forename: James A
authors.initials: JA
authors.lastname: Russell
authors.forename: A Robert
authors.initials: AR
authors.lastname: Turner
authors.forename: Loree
authors.initials: L
authors.lastname: Larratt
authors.forename: Ahsan
authors.initials: A
authors.lastname: Chaudhry
authors.forename: Donald
authors.initials: D
authors.lastname: Morris
authors.forename: Christopher
authors.initials: C
authors.lastname: Brown
authors.forename: Diana
authors.initials: D
authors.lastname: Quinlan
authors.forename: Douglas
authors.initials: D
authors.lastname: Stewart
mesh_terms: D000293:Adolescent; D000328:Adult; D000961:Antilymphocyte Serum / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002066:Busulfan / Q000627:therapeutic use; D006086:Graft vs Host Disease / Q000401:mortality / Q000473:pathology / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000401:mortality / Q000628:therapy*; D006648:Histocompatibility; D006801:Humans; D016555:Matched-Pair Analysis; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000627:therapeutic use; D036102:Peripheral Blood Stem Cell Transplantation / Q000379:methods*; D015996:Survival Rate; D019172:Transplantation Conditioning / Q000379:methods*; D014740:Vidarabine / Q000031:analogs & derivatives / Q000627:therapeutic use; D014916:Whole-Body Irradiation
chemical_list: D000961:Antilymphocyte Serum; D019653:Myeloablative Agonists; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine