Department of Nuclear Medicine, University Hospital Münster, Münster, Germany.
Department of Medicine A, Hematology, Oncology and Pulmonary Medicine, University Hospital Münster, Münster, Germany.
Transplant Cell Ther. 2021 Jul;27(7):603-610. doi: 10.1016/j.jtct.2021.04.011. Epub 2021 Apr 25.
Graft-versus-host disease (GVHD) is a common complication that increases morbidity and mortality after allogeneic stem cell transplantation (allo-SCT). Fluorodeoxyglucose F 18 (F-FDG)-positron emission tomography (PET) imaging has been demonstrated to be highly informative for evaluating and mapping of intestinal GVHD. To corroborate and extend existing findings and to investigate whether glucose metabolism assessed by F-FDG-PET might be an effective diagnostic tool to predict corticosteroid-refractory acute GVHD and overall survival. In this retrospective analysis, 101 patients with clinically suspected acute intestinal GVHD underwent F-FDG-PET between June 2011 and February 2019. Seventy-four of these patients with clinically and/or histologically proven acute intestinal GVHD as well as positive F-FDG-PET findings were analyzed in detail to assess the predictive value of F-FDG-PET regarding the response to immunosuppressive therapy and survival. Quantitative PET parameters, particularly the maximum standard uptake value (SUVmax), of patients with a fast response (ie, clinical improvement and decreased GVHD activity by at least 1 stage after 1 week of GVHD treatment) or slow/no response (ie, persistent disease activity for more than 1 week or increasing GVHD activity following first-line immunosuppressive therapy) were evaluated. F-FDG-PET detected intestinal GVHD with a sensitivity of 93% (95% confidence interval [CI], 85% to 97%) and specificity of 73% (95% CI, 45% to 91%). Patients with a fast response to immunosuppressive therapy had a mean SUVmax of 13.7 (95% CI, 11.0 to 16.5) compared with 7.6 (95% CI, 7.0 to 8.3; P = .005) observed in patients with prolonged or no response. The median overall survival (OS) was 573.0 days (95% CI, 539.5 to 606.5 days) for patients with fast response versus 255 days (95% CI, 161.0 to 349.0 days; P = .009) for patients with slow or no responses. A SUVmax threshold >8.95 applied to F-FDG-PET performed within 100 days after transplantation identified patients with a median OS of 390 versus 117 days for patients with SUVmax ≤8.95 (P = .036). SUVmax threshold and donor type were independent factors for OS. Our results indicate that F-FDG-PET is highly accurate in identifying patients with acute intestinal GVHD and may predict responses to immunosuppressive therapy as well as survival, particularly when applied within the first 100 days after transplantation. These results provide a strong rationale to integrate PET imaging in future prospective trials evaluating new therapies for acute GVHD.
移植物抗宿主病(GVHD)是异基因造血干细胞移植(allo-SCT)后常见的并发症,增加发病率和死亡率。氟脱氧葡萄糖 F18(F-FDG)-正电子发射断层扫描(PET)成像已被证明对评估和定位肠道 GVHD 具有高度信息性。为了证实和扩展现有发现,并研究葡萄糖代谢评估 F-FDG-PET 是否可以成为预测皮质类固醇难治性急性 GVHD 和总生存的有效诊断工具。在这项回顾性分析中,101 例临床疑似急性肠道 GVHD 患者在 2011 年 6 月至 2019 年 2 月期间接受了 F-FDG-PET 检查。对其中 74 例具有临床和/或组织学证实的急性肠道 GVHD 以及 F-FDG-PET 阳性发现的患者进行了详细分析,以评估 F-FDG-PET 对免疫抑制治疗反应和生存的预测价值。评估了快速反应(即,在 GVHD 治疗后 1 周内临床改善和 GVHD 活动至少降低 1 期)或缓慢/无反应(即,持续疾病活动超过 1 周或在一线免疫抑制治疗后 GVHD 活动增加)患者的定量 PET 参数,特别是最大标准摄取值(SUVmax)。
F-FDG-PET 检测肠道 GVHD 的敏感性为 93%(95%置信区间[CI],85%至 97%),特异性为 73%(95% CI,45%至 91%)。与对免疫抑制治疗无反应或反应缓慢的患者相比(SUVmax 为 7.6[95% CI,7.0 至 8.3]),对免疫抑制治疗有快速反应的患者 SUVmax 均值为 13.7(95% CI,11.0 至 16.5)。对免疫抑制治疗有快速反应的患者的中位总生存(OS)为 573.0 天(95% CI,539.5 至 606.5 天),而对免疫抑制治疗缓慢或无反应的患者的中位 OS 为 255 天(95% CI,161.0 至 349.0 天;P=.009)。在移植后 100 天内进行的 F-FDG-PET 中 SUVmax 阈值>8.95 可识别出中位 OS 为 390 天的患者,而 SUVmax≤8.95 的患者为 117 天(P=.036)。SUVmax 阈值和供体类型是 OS 的独立因素。
我们的研究结果表明,F-FDG-PET 对急性肠道 GVHD 的识别具有高度准确性,并且可以预测对免疫抑制治疗的反应以及生存,尤其是在移植后 100 天内应用时。这些结果为在评估急性 GVHD 新疗法的未来前瞻性试验中整合 PET 成像提供了强有力的理由。