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Anti-thymocyte globulin (ATG) is often incorporated into allogeneic stem cell transplant (alloHCT) conditioning regimens to prevent graft-versus-host disease (GVHD). Literature regarding the effect of ATG on outcomes is mixed; some data suggests an improvement in GVHD control with ATG use, but other data shows a reduction in overall survival, particularly in the reduced intensity setting. This study evaluates the impact of ATG on infection, GVHD, relapse, and mortality rates in adult alloHCT patients.
Methods
A retrospective review of 250 adult alloHCT patients at our institution (125 unrelated/mismatched donor recipients received ATG, 125 matched related donors did not) between 2006 and 2013 was performed. Charts were reviewed for ATG use, demographics, infections (bacterial, viral, fungal), infection source, GVHD, day-180 relapse, and day-180 mortality. The primary endpoint was infection rate; secondary endpoints included mortality and GVHD.
Results
Factors with significant impact on infection incidence were conditioning type (Myeloablative (MAC) > Reduced Intensity (RIC), p=0.0105), age (p=0.0245), and use of ATG (p=0.0185). MAC was associated with greater incidence of infection (median 3 infections vs. RIC median 2 infections, p=0.0001). Infection incidence was significantly increased in patients receiving ATG compared to those not receiving ATG (median 3 vs. 2, p=0.0003). The relative increase in infections with ATG was more pronounced in RIC (+ATG median 3 vs –ATG median 1) than in MAC (+ATG median 4 vs. –ATG median 3). In both RIC and MAC, ATG use was associated with increased numbers of CMV (112 vs. 61), HHV6 (47 vs. 13), and HSV (32 vs. 8) infections. The relative increase in infection incidence for +ATG patients in RIC (CMV 2.5-fold, HHV6 10.5-fold, HSV 6.5-fold increase) was greater than the increase seen for +ATG patients in MAC (CMV 1.46-fold, HHV6 2.36-fold, HSV 3.17-fold increase).
Similar rates of severe (grade 3-4) aGVHD were observed in + ATG patients compared to –ATG patients (17.5% vs. 14.95%, p=0.72) through day 180, indicating a potential protective effect of ATG in unrelated/mismatched transplants. In RIC, a nonsignificantly greater proportion of +ATG patients developed severe aGVHD (19.4%) compared to –ATG patients (12.9%).
The rates of relapse/death were not different between ATG groups (29.91% for –ATG and 39.68% for +ATG), and groups had similar mean times to relapse (148 days for –ATG and 138 days for +ATG). At 180 days, survival was 83.2% for –ATG and 71.4% for +ATG (p=0.0426).
Conclusion
Our study demonstrates that ATG use increases infection rates in alloHCT patients, with greater impact in the RIC setting. Although relapse rates were similar between groups, the 180-day mortality for +ATG was significantly greater than –ATG, suggesting that infectious complications may impact mortality associated with ATG.