The Blood and Marrow Transplant Program at Northside Hospital, Bone Marrow Transplant Group of Georgia, Atlanta, GA, USA.
Department of Mathematics and Statistics, Georgia State University, Atlanta, GA, USA.
Bone Marrow Transplant. 2014 May;49(5):616-21. doi: 10.1038/bmt.2014.2.
Although pretransplant alemtuzumab can reduce GVHD following allogeneic transplantation, it may also increase the risk of mixed donor T-cell chimerism and infections. We hypothesized that the early use of DLI without withdrawal of immunosuppressive drugs in patients with mixed T-cell chimerism would lower the risk of relapse without significantly increasing the risk of GVHD post DLI. Thirty-six patients (median age 59 years) were treated in this phase II trial using reduced-intensity conditioning including s.c. alemtuzumab (total dose 43 mg) and a PBSC graft from a matched unrelated donor (UD). DLI without withdrawal of immunosuppressive drugs was administered to all 25 patients with <50% donor T-cell chimerism on day +60. The cumulative risks of acute and chronic GVHD were 42% and 59%, respectively. Estimated probabilities of non-relapse mortality (NRM) at day 100 and 1 year were 3% and 14%, respectively. With a median follow up 2.4 years, estimated survivals at day 100, 1 and 2 years were 97%, 71% and 57%, respectively. In multivariate analysis, the occurrence of acute GVHD was associated with an increased risk of mortality, whereas the occurrence of chronic GVHD had a protective effect, associated with decreased relapse and improved disease-free survival. Low-dose alemtuzumab and preemptive DLI provides favorable transplant outcomes including low NRM in an older patient population with high-risk malignancies undergoing UD transplantation.
虽然移植前阿仑单抗可降低异基因移植后的移植物抗宿主病（GVHD），但它也可能增加混合供体细胞嵌合和感染的风险。我们假设，在混合 T 细胞嵌合患者中，早期使用不撤回免疫抑制药物的 DLI 会降低复发风险，而不会显著增加 DLI 后 GVHD 的风险。在这项 II 期试验中，36 名患者（中位年龄 59 岁）接受了包括皮下注射阿仑单抗（总剂量 43mg）和来自匹配的无关供体（UD）的 PBSC 移植物在内的低强度预处理。在第+60 天，所有 25 名混合嵌合率<50%的患者均给予不撤回免疫抑制药物的 DLI。急性和慢性 GVHD 的累积风险分别为 42%和 59%。100 天和 1 年的非复发死亡率（NRM）估计概率分别为 3%和 14%。中位随访 2.4 年后，100 天、1 年和 2 年的估计生存率分别为 97%、71%和 57%。在多变量分析中，急性 GVHD 的发生与死亡率增加相关，而慢性 GVHD 的发生具有保护作用，与降低复发和改善无病生存相关。低剂量阿仑单抗和预防性 DLI 为老年高危恶性肿瘤患者接受 UD 移植提供了有利的移植结果，包括低 NRM。
