Background: Immune biomarkers such as Quantiferon®-Monitor (QFM) are being evaluated as a novel method for measuring immunosuppression and predicting infection in lung transplant (LT) recipients. Our prior prospective cohort study found low QFM values were associated with more immunosuppression and predicted serious opportunistic infections (OI’s) between 3-12 months post-transplant. The aim of this study was to examine the second post-transplant year and beyond, exploring relationships between QFM and longer-term clinical outcomes including infection, rejection and mortality.
Methods: Patients were prospectively recruited between 2015-2017. QFM was tested before & at 2, 6, 12, 24 & 52 weeks post-LT. Standard immunosuppression included tacrolimus, azathioprine, prednisone & basiliximab in patients with limited renal reserve. Patients were assessed over the second post-transplant year for infection and rejection then for long-term survival. Infections were classified as serious if hospitalization was required and OI if caused by a pathogen that does not usually affect healthy individuals.
Results: 75/80 patients originally recruited who survived beyond the first year were included. Median age was 61 years, 45 (60%) were male, 65 (87%) underwent bilateral LT and 37 (50%) received induction basiliximab. Median QFM values at 12 months were 178 IU/mL (IQR 36-440). 33/75 (44%) died at a median of 4 years post-transplant (IQR 2.5-5.7). Median follow-up amongst the survivors was 6.6 years (IQR 6.5-6.8). Median QFM values were slightly lower amongst patients who later died (162 IU/mL, IQR 39-351 vs. 208, 36-454, p=0.64). 52 patients (69%) experienced total of 139 infection episodes in year 2, including 52 serious infections and 23 OI’s. The most common pathogens were fungi (n=16) and cytomegalovirus (n=31). Serious OI’s were rare in year 2, with 15 episodes in 9 patients. Median QFM values at 12 months were lower in patients who developed serious OI (86, 43-280 vs. 190, 35-458 IU/mL, p=0.40). Patients testing <87 IU/mL were more likely to develop serious OI, although this also did not reach statistical significance (HR 2.46, 95% CI 0.66-9.16, p=0.18). Patients who experienced a serious OI during the first two years post-transplant had higher mortality (58% vs. 31%, HR 2.31, 95% CI 1.13-4.70, p=0.02).
Conclusions: Our prior study demonstrated the potential of QFM to identify overly immunosuppressed patients at risk for serious OI’s within the first year post-transplant. During the second year, serious OI’s were infrequent and therefore while findings were overall consistent with our prior results, there was insufficient power to reach statistical significance. Importantly, serious OI’s were associated with increased long-term mortality. QFM may offer the opportunity to identify these high-risk individuals early with a potential window for intervention that might be able to improve not only their short-term morbidity but also long-term survival.