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Background: Anti-thymocyte globulin (ATG) may be used as part of the conditioning regimen in allogeneic stem cell transplant to reduce severe graft-versus-host disease (GVHD) and to improve engraftment. However, the use of ATG in this setting has been associated with delayed immune reconstitution that may lead to reactivation of viral infections. Here, we investigated the effect of ATG on the reactivation of multiple viral infections and the incidence of acute and chronic GVHD in those who received matched-unrelated donor (MUD), matched-related donor (MRD) or double umbilical cord blood transplants (CB).
Methods: We reviewed the medical records of 117 patients undergoing allogeneic stem cell transplants at University Hospitals Seidman Cancer Center between 2010 and 2013. The data collected include demographics, graft source, conditioning regimen, ATG (types/total dose: rabbit: 3 mg/kg, 6 mg/kg or 7.5 mg/kg and equine: 60 mg/kg or 90 mg/kg), GVHD prophylaxis regimen, viral infection status before and after transplant, acute and chronic GVHD, death and relapse. ATG was only administered to MUD and CB, but not MRD recipients. The cumulative incidence of CMV, EBV, HHV-6 or HHV-8 viremia (PCR copy > 1000), acute and chronic GVHD was estimated with death as the competing risk. Two-sided p-values ² 0.05 were considered statistically significant. Serum viral load was prophylactically monitored by PCR weekly.
Results: Of 117 allogeneic stem cell transplants, 39 were MUD, 31 were MRD and 47 were CB. 77 transplants received reduced-intensity conditioning regimen while others were myeloablative. 12 graft failures were excluded from the analysis. Among the remaining 105 transplants, there was no significant difference in the reactivation of CMV, EBV or HHV-8 in patients treated with ATG compared with patients not receiving ATG. Cumulative incidence of HHV-6 reactivation was significantly higher in ATG recipients by day 100 post-transplant (42.9 vs 13.9, p=0.002) (Figure 1). HHV-6 reactivation in CB transplants was higher as early as by day 30 when compared with MUD or MRD recipients (43 vs 10.5 vs 6.7, p<0.0001). No central nervous system manifestations of HHV-6 was observed. Cumulative incidence for overall acute GVHD and grade III-IV acute GVHD in patients receiving ATG and those who did not by day 100 was 42.5 versus 50.6 (p=0.128) and 4.8 versus 12.5 (p=0.145), respectively. In addition, cumulative incidence of chronic GVHD was lower in the ATG group by day 365 (32.1 vs 55.6) although not statistically significant (p=0.192).
Figure 1. Cumulative incidence of HHV-6 in ATG and non-ATG recipients
Conclusion: ATG use as part of a conditioning regimen in our allogeneic stem cell transplant cohort was associated with post-transplant HHV-6 reactivation, but not CMV, EBV or HHV-8 although the clinical significance of this finding was unclear.