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: Mehdi Hamadani, William Blum, Gary Phillips, Patrick Elder, Leslie Andritsos, Craig Hofmeister, Lynn O'Donnell, Rebecca Klisovic, Sam Penza, Ramiro Garzon, David Krugh, Thomas Lin, Thomas Bechtel, Don M Benson, John C Byrd, Guido Marcucci, Steven M Devine
• Journal: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation (Biol Blood Marrow Transplant) Vol. 15 Issue 11 Pg. 1422-30 (Nov 2009) ISSN: 1523-6536 [Electronic] United States
• PMID: 19822302 (Publication Type: Clinical Trial, Journal Article)

Chemical References

• Anti-Infective Agents
• Antilymphocyte Serum
• Immunosuppressive Agents
• Myeloablative Agonists
• Vidarabine
• Busulfan
• fludarabine
• Tacrolimus
• Methotrexate

Topics

• Adult
• Aged
• Animals
• Anti-Infective Agents (therapeutic use)
• Antilymphocyte Serum (administration & dosage, adverse effects)
• Busulfan (administration & dosage)
• Disease Susceptibility
• Female
• Graft vs Host Disease (drug therapy, etiology, prevention & control)
• Hematologic Neoplasms (mortality, surgery)
• Hematopoietic Stem Cell Transplantation (adverse effects, mortality, statistics & numerical data)
• Humans
• Immunocompromised Host
• Immunosuppressive Agents (administration & dosage, adverse effects)
• Infection Control
• Infections (epidemiology, etiology)
• Male
• Medical Audit
• Methotrexate (administration & dosage)
• Middle Aged
• Myeloablative Agonists (administration & dosage)
• Patient Isolation
• Postoperative Complications (epidemiology, etiology, prevention & control)
• Rabbits
• T-Lymphocytes
• Tacrolimus (administration & dosage)
• Transplantation Conditioning (methods)
• Transplantation, Homologous
• Vidarabine (administration & dosage, analogs & derivatives)
• Young Adult