title: Improved nonrelapse mortality and infection rate with lower dose of antithymocyte globulin in patients undergoing reduced-intensity conditioning allogeneic transplantation for hematologic malignancies.
abstract: We sought to reduce the risk of infectious complications and nonrelapse mortality (NRM) associated with the use of antithymocyte globulin (ATG) without compromising control of acute graft-versus-host disease (aGVHD) in patients undergoing reduced-intensity conditioning (RIC) transplantation. As part of an ongoing quality improvement effort, we lowered the dose of rabbit ATG from 7.5 mg/kg of ATG (R-ATG) (n = 39) to 6.0 mg/kg of ATG (r-ATG) (n = 33) in association with fludarabine (Flu) and busulfan (BU) RIC transplantation and then monitored patients for adverse events, relapse, and survival. Of the 72 mostly high risk (82%) patients studied, 89% received unrelated donor allografts, 25% of which were HLA-mismatched. No differences in posttransplantation full donor-cell chimerism rates were observed between the 2 ATG-dose groups (P > .05). When R-ATG versus r-ATG patients were compared, we observed no significant difference in the cumulative incidence of grade II-IV aGVHD (32% versus 27%; P = .73) or grade III-IV aGVHD (23% versus 11%; P = .28). However, the r-ATG group had significantly less cytomegalovirus (CMV) reactivation (64% versus 30%; P = .005) and bacterial infections (56% versus 18%; P = .001), a better 1-year cumulative incidence of NRM (18% versus 3%; P = .03), and a trend for better 1-year overall survival (OS) (64% versus 84%; P = .07) compared to R-ATG patients. A seemingly modest reduction in the dose of rabbit ATG did not compromise control of aGVHD or achievement of donor chimerism, but led to a significant decrease in the risk of serious infections and NRM in high-risk RIC allograft recipients.
authors.affiliation: Division of Hematology/Oncology, Blood and Marrow Transplantation Section, and Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA. mehdi.hamadani@gmail.com
authors.forename: Mehdi
authors.initials: M
authors.lastname: Hamadani
authors.forename: William
authors.initials: W
authors.lastname: Blum
authors.forename: Gary
authors.initials: G
authors.lastname: Phillips
authors.forename: Patrick
authors.initials: P
authors.lastname: Elder
authors.forename: Leslie
authors.initials: L
authors.lastname: Andritsos
authors.forename: Craig
authors.initials: C
authors.lastname: Hofmeister
authors.forename: Lynn
authors.initials: L
authors.lastname: O'Donnell
authors.forename: Rebecca
authors.initials: R
authors.lastname: Klisovic
authors.forename: Sam
authors.initials: S
authors.lastname: Penza
authors.forename: Ramiro
authors.initials: R
authors.lastname: Garzon
authors.forename: David
authors.initials: D
authors.lastname: Krugh
authors.forename: Thomas
authors.initials: T
authors.lastname: Lin
authors.forename: Thomas
authors.initials: T
authors.lastname: Bechtel
authors.forename: Don M
authors.initials: DM
authors.lastname: Benson
authors.forename: John C
authors.initials: JC
authors.lastname: Byrd
authors.forename: Guido
authors.initials: G
authors.lastname: Marcucci
authors.forename: Steven M
authors.initials: SM
authors.lastname: Devine
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D000890:Anti-Infective Agents / Q000627:therapeutic use; D000961:Antilymphocyte Serum / Q000008:administration & dosage* / Q000009:adverse effects; D002066:Busulfan / Q000008:administration & dosage; D004198:Disease Susceptibility; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000401:mortality / Q000601:surgery*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000401:mortality / Q000706:statistics & numerical data*; D006801:Humans; D016867:Immunocompromised Host; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D017053:Infection Control; D007239:Infections / Q000453:epidemiology* / Q000209:etiology; D008297:Male; D008485:Medical Audit; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000008:administration & dosage*; D010356:Patient Isolation; D011183:Postoperative Complications / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D011817:Rabbits; D013601:T-Lymphocytes; D016559:Tacrolimus / Q000008:administration & dosage; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives; D055815:Young Adult
chemical_list: D000890:Anti-Infective Agents; D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D019653:Myeloablative Agonists; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine; D016559:Tacrolimus; D008727:Methotrexate