Fluorine-18-Fluorodeoxyglucose Positron Emission Tomography for the Assessment of Acute Intestinal GvHD and Prediction of Response to Immunosuppressive Therapy

Introduction: Graft-versus-Host disease (GvHD) is a common complication significantly increasing morbidity and mortality after allogeneic stem cell transplantation (allo-SCT). ¹⁸F-FDG-PET imaging has demonstrated to be highly informative for evaluating and mapping of intestinal GvHD (Stelljes et al., BLOOD 2008). We hypothesized that this diagnostic tool might have predictive value with regard to response to therapies and overall outcome for patients with acute intestinal GvHD.

Methods: In this retrospective analysis, 101 patients at our center with clinically suspected acute intestinal GvHD were studied using ¹⁸F-FDG-PET between 6/2011 and 2/2019. 74 of these patients with clinically and/or histologically proven acute intestinal GVHD as well as positive ¹⁸F-FDG-PET findings were analyzed in detail, to assess the predictive value of ¹⁸F-FDG-PET regarding response to immunosuppressive therapy and survival. Quantitative PET parameters, particular the maximum standard uptake value (SUVmax), of patients with fast (clinical improved with decreased GvHD activity of at least 1 stage within one week after start of GvHD treatment) or slow/no responses (persisting activity for more than 1 week or increasing GvHD activity following first line therapy to immunosuppressive therapy) were evaluated.

Results: ¹⁸F-FDG-PET detected clinically proven intestinal GvHD with a sensitivity of 93% (95% CI: 85-97%) and a specificity of 73% (95% CI: 45-91%). Patients that responded to first line treatment of GvHD had mean SUVmax of 13.7 (95% CI: 11.0-16.5) compared mean SUVmax 7.6 (95% CI: 7.0-8.3) observed in patients with prolonged or no response. Consequently, ¹⁸F-FDG-PET had a statistically significant predictive value (p .005) with regard to response to immunosuppressive treatment. Overall survival (OS) at 12 months after allo-SCT for patients with fast response to immunosuppressive therapy was 67% (95% CI: 45-89%) and 33% (95% CI: 20.4-46.0; p .005) in patients with slow or no responses. In addition, a SUVmax threshold of greater than 8.95 applied to ¹⁸F-FDG-PET performed within 100 days after transplantation might identify patients with a higher OS, with a median OS of 390 days versus 117 days for patients with SUVmax ≤ 8.95 (p .036). In multivariate analyses, the SUVmax threshold (hazard ratio, 0.47; 95% CI, 0.23 to 0.95) and related versus unrelated donor (hazard ratio, 0.22; 95% CI, 0.05 to 0.90) were independent factors for survival outcome in our cohort.

Conclusion: Our results indicate that ¹⁸F-FDG-PET is highly sensitive and specific in identifying patients with acute intestinal GvHD and might predict responses to immunosuppressive therapy as well as survival outcome, particularly when applied within the first 100 days after transplant. These results provide a strong rationale to integrate PET-imaging in future prospective trials evaluating new therapies for acute GvHD.