Department of Hematology, Radboud University Nijmegen Medical Centre, Geert Grooteplein 8, Nijmegen, The Netherlands.
Biol Blood Marrow Transplant. 2010 Mar;16(3):320-32. doi: 10.1016/j.bbmt.2009.10.006. Epub 2009 Oct 14.
Allogeneic stem cell transplantation (SCT) in multiple myeloma (MM) may induce a curative graft-versus-myeloma (GVM) effect. Major drawback in unmanipulated reduced-intensity conditioning (RIC) SCT is the risk of severe and longstanding graft-versus-host-disease (GVHD). This study demonstrates that transplantation with a partial T cell-depleted graft creates a platform for boosting GVM immunity by preemptive donor lymphocyte infusion (DLI) and recipient dendritic cell (DC) vaccination, with limited GVHD. All 20MM patients engrafted successfully. Chimerism analysis in 19 patients evaluable at 3 months revealed that 7 patients were complete donor, whereas 12 patients were mixed chimeric. Grade II acute GVHD (aGVHD) occurred in 7 patients (35%) and only 4 patients (21%) developed chronic GVHD (cGVHD). Fourteen patients received posttransplantation immunotherapy, 8 preemptive DLI, 5 patients both DLI and DC vaccination, and 1 patient DC vaccination only. DC vaccination was associated with limited toxicity, and none of these patients developed GVHD. Importantly, overall treatment-related mortality (TRM) at 1 year was low (10%). Moreover, the overall survival (OS) is 84% with median follow-up of 27 months, and none of the patients died from progressive disease. These findings illustrate that this novel approach is associated with limited GVHD and mortality, thus creating an ideal platform for adjuvant immunotherapy.
异基因造血干细胞移植（SCT）在多发性骨髓瘤（MM）中可能诱导出治愈性移植物抗骨髓瘤（GVM）效应。未处理的减低强度预处理（RIC）SCT 的主要缺点是发生严重和长期移植物抗宿主病（GVHD）的风险。本研究表明，使用部分 T 细胞耗竭的移植物进行移植为通过抢先供者淋巴细胞输注（DLI）和受者树突状细胞（DC）疫苗接种来增强 GVM 免疫创造了一个平台，同时GVHD 有限。所有 20 例 MM 患者均成功植入。在可评估 3 个月的 19 例患者中进行嵌合分析，发现 7 例患者完全为供者，而 12 例患者为混合嵌合。7 例（35%）患者发生 II 级急性 GVHD（aGVHD），仅 4 例（21%）患者发生慢性 GVHD（cGVHD）。14 例患者接受移植后免疫治疗，8 例患者接受抢先 DLI，5 例患者同时接受 DLI 和 DC 疫苗接种，1 例患者仅接受 DC 疫苗接种。DC 疫苗接种与有限的毒性相关，这些患者均未发生 GVHD。重要的是，1 年时总治疗相关死亡率（TRM）较低（10%）。此外，中位随访 27 个月时的总生存率（OS）为 84%，无患者死于进展性疾病。这些发现表明，这种新方法与有限的 GVHD 和死亡率相关，从而为辅助免疫治疗创造了一个理想的平台。
