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.

Figures

Figure 1

Cumulative incidence of GVHD according to the ATG dosage group. (A) cumulative incidence of grade II–IV acute GVHD, (B) cumulative incidence of grade III–IV acute GVHD, (C) cumulative incidence of chronic GVHD and (D) cumulative incidence of extensive chronic GVHD. Solid curves represent patients receiving ATG at 6.0mg/kg, while the dashed curves represent patient getting the 7.5mg/kg ATG dose.

Figure 2

(A) Cumulative incidence of non-relapse mortality according to the ATG dosage group. (B) Cumulative incidence of disease relapse according to the ATG dosage group. Solid curves represent patients receiving ATG at 6.0mg/kg, while the dashed curves represent patient getting the 7.5mg/kg ATG dose.

Figure 3

Overall survival and progression free survival according to ATG dosage group. (A) Kaplan-Meier estimates of overall survival following allogeneic transplantation, (B) Kaplan-Meier estimates of progression free survival following allogeneic transplantation. Solid curves represent patients receiving ATG at 6.0mg/kg, while the dashed curves represent patient getting the 7.5mg/kg ATG dose.