Predicting Risk of Infection and Graft vs. Host Disease (GvHD), and Response to Immunosuppression (ISP) in Allogeneic Hematopoietic Stem Cell Transplant (HSCT) Patients (pts) Using the Cylex®ImmuKnow® Assay: A Pilot Study.

Background: GvHD, intensity of ISP and infection are major causes of toxicity post-HSCT. Yet, no method reliably predicts these complications. A functional assay for immunity, which predicts risk of GvHD and infection and allows tailoring ISP and infection prophylaxis, is needed. The ImmuKnow is an assay of global T-cell function that measures increased ATP production after stimulating CD4+ T-helper cells and has been shown useful for managing ISP therapies in solid-organ transplantation. We hypothesized that ImmuKnow could assist in predicting risk of GvHD and infection and response to ISP post-HSCT.

Patients and Methods: Between January 2003 and May 2006, 34 adult allogeneic HSCT pts [mean age 47 years (range 22–71); 53% females; acute myelogenous leukemia, 8 pts; myeloma, 6 pts;] underwent blood sampling for determining ImmuKnow at various times post-HSCT (238 assays, mean of 7/pt). Results were correlated with clinical course (infection, stable, GvHD, response to ISP).

Results: During the testing period, GvHD was documented in 16 pts [(acute, n=7 pts; chronic, n=9 pts] and 53 infections occurred [CMV viremia (n=20); bacteremia (n=20); others (n=13)]. The median immune function (ng/mL ATP) of GvHD pts was significantly higher than that of clinically stable pts (342 +/−105 vs. 167 ng/mL +/−136 respectively), p<0.001. Pts with infections had a median 89 ng/mL ATP (+/−119), also statistically different (p=0.002) from stable pts. A pt with ATP value ≥ 300 ng/mL was more likely (RR=4) to develop GvHD than one with lower immune response. Similarly, there was a higher risk (RR=5) for infection in pts with an ATP ≤ 80 ng/mL. Relative risk curves for infection and GvHD intersected in the low immune response zone (140 ng/mL ATP). Following therapy for GvHD in 10 pts, ATP values rapidly decreased (193 ng/mL ATP +/−122) over 17 days (range 3–35) and were associated with improvement, while stable or increasing values (50 ng/mL ATP +/−99) were observed among 6 pts who failed to respond to GvHD therapy.

Conclusions: these data suggest that the FDA-approved ImmuKnow assay is an objective marker of risk for infection and GvHD, and of responsiveness to ISP therapy post-HSCT. Tailoring intensity and duration of ISP to risks of GvHD and infection in an individual pt may be possible and may improve outcomes. Validation of these preliminary data is ongoing.