Stadler Michael, Venturini Letizia, Bünting Ivonne, Dammann Elke, Weissinger Eva M, Schwarzer Adrian, Schultze-Florey Christian, Ehrlich Steve, Markel Dominik, Lueck Catherina, Gladysz Alexandra, Fröhlich Tabea, Damrah Nouraldin, Beutel Gernot, Eder Matthias, Ganser Arnold, Hambach Lothar
Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
Front Oncol. 2022 Aug 17;12:867356. doi: 10.3389/fonc.2022.867356. eCollection 2022.
Preemptive and therapeutic donor lymphocyte infusions (preDLI and tDLI) are widely used in relapsing and relapsed hematopoietic malignancies after allogeneic stem cell transplantation (alloSCT) to enhance the graft-versus-malignancy effect. However, in advanced myeloid malignancies, long-term survival after preDLI and tDLI remains low, reflecting our inability to master the double-edged sword of alloreactivity, balancing anti-neoplastic activity versus graft-versus-host disease (GvHD). We previously evaluated a quantitative PCR-based high-sensitivity chimerism (hs-chimerism) based on insertion/deletion polymorphisms instead of short tandem repeats, where increasing host chimerism in peripheral blood predicts relapse more than a month before clinical diagnosis, and declining host chimerism signals anti-host alloreactivity. Here we report 32 consecutive patients with advanced myeloid malignancies receiving preDLI or tDLI "navigated" by hs-chimerism ("navigated DLI"). We compared them to a historical cohort of 110 consecutive preDLI or tDLI recipients, prior to implementation of hs-chimerism at our institution ("controls"). Both groups were comparable regarding age, gender, conditioning, donor type, and time to DLI. With longer median follow-up of the navigated DLI group (8.5 versus 5 months), their landmark overall (64%) and disease-free survival (62%) at 2 years from first DLI compared favorably with controls (23% and 21%, respectively). Improved survival of navigated DLI was due to both reduced relapse incidence (38% versus 60%) and non-relapse mortality (17% versus 44%) at 2 years. Early relapse prediction by hs-chimerism allowed a preemptive approach in 28% of navigated DLI versus 7% in controls. Our results confirm hs-chimerism as a highly valuable tool for monitoring and steering immune interventions after alloSCT.
预防性和治疗性供体淋巴细胞输注（preDLI和tDLI）广泛应用于异基因干细胞移植（alloSCT）后复发和难治性血液系统恶性肿瘤，以增强移植物抗恶性肿瘤效应。然而，在晚期髓系恶性肿瘤中，preDLI和tDLI后的长期生存率仍然很低，这反映出我们无法掌控同种异体反应性这把双刃剑，难以平衡抗肿瘤活性与移植物抗宿主病（GvHD）。我们之前评估了一种基于插入/缺失多态性而非短串联重复序列的定量PCR高灵敏度嵌合分析（hs-嵌合分析），外周血中宿主嵌合率增加预示着临床诊断前一个多月会复发，而宿主嵌合率下降则表明存在抗宿主同种异体反应性。在此，我们报告了32例接受基于hs-嵌合分析“导航”的preDLI或tDLI（“导航DLI”）的晚期髓系恶性肿瘤患者。我们将他们与我们机构在实施hs-嵌合分析之前连续110例接受preDLI或tDLI的患者组成的历史队列（“对照组”）进行比较。两组在年龄、性别、预处理方案、供体类型和接受DLI的时间方面具有可比性。导航DLI组的中位随访时间更长（8.5个月对5个月），其从首次DLI起2年时的标志性总生存率（64%）和无病生存率（62%）优于对照组（分别为23%和21%）。导航DLI生存率的提高归因于2年时复发率降低（38%对60%）和非复发死亡率降低（17%对44%）。hs-嵌合分析对早期复发的预测使得28%的导航DLI患者能够采取抢先治疗方法，而对照组这一比例为7%。我们的结果证实hs-嵌合分析是alloSCT后监测和指导免疫干预的极有价值的工具。
