Peking University Peoples Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China; Collaborative Innovation Center of Hematology, Beijing, China.
Nanfang Hospital, Southern Medical University, Beijing, China.
Biol Blood Marrow Transplant. 2017 Aug;23(8):1311-1319. doi: 10.1016/j.bbmt.2017.04.028. Epub 2017 May 5.
Patients with refractory/relapsed acute leukemia who have received allogeneic hematopoietic stem cell transplantation (allo-HSCT) are still at a high risk for relapse post-transplant. To investigate the impact of prophylactic donor lymphocyte infusion (DLI) followed by minimal residual disease (MRD) test and graft-versus-host disease (GVHD)-guided multiple DLIs to prevent relapse and improve survival in patients with refractory/relapsed acute leukemia who received allo-HSCT. A multicenter prospective study was designed. In total, 100 patients who achieved complete remission at 30 days post-transplant and had no uncontrolled infection, organ failure, or active GVHD were eligible First, prophylactic DLI was administered at 30 days after HLA-matched related HSCT or 45 to 60 days after HLA-matched unrelated HSCT or haploidentical HSCT. Subsequently, multiple DLIs were administered based on the results of MRD test and whether they developed GVHD. In addition to DLI, chemotherapy was also given to patients who had a positive MRD test. Three-year cumulative incidence of relapse, leukemia-free survival, and survival post-transplant were 32.4% (95% confidence interval, 22.4% to 42.4%), 50.3% (95% confidence interval, 40.3% to 60.3%), and 51.4% (95% confidence interval, 41.2% to 61.6%), respectively. In multivariate analysis, a positive MRD test (HR, 3.840; 95% confidence interval, 1.678 to 5.784; P= .001) and receiving 1 course of DLI (HR, 4.346; 95% confidence interval, 1.223 to 9.450, P= .023) were associated with an increased relapse risks. These data suggest that prophylactic DLI followed by MRD test and GVHD-guided multiple DLIs reduced relapse and increased survival post-transplant in patients with refractory/relapsed acute leukemia who received allo-HSCT. The study is registered at www.ClinicalTrials.gov as NCT01455272.
接受异基因造血干细胞移植（allo-HSCT）的难治/复发急性白血病患者在移植后仍有很高的复发风险。为了研究预防性供者淋巴细胞输注（DLI）继以微小残留病（MRD）检测和移植物抗宿主病（GVHD）指导的多次 DLI 预防复发和改善难治/复发急性白血病患者allo-HSCT 后的生存情况，进行了一项多中心前瞻性研究。共纳入 100 例移植后 30 天达完全缓解且无未控制感染、器官衰竭或活动性 GVHD 的患者。首先，在 HLA 匹配的相关 HSCT 后 30 天或 HLA 匹配的无关 HSCT 或单倍体 HSCT 后 45-60 天给予预防性 DLI。随后，根据 MRD 检测结果和是否发生 GVHD 给予多次 DLI。除 DLI 外，MRD 检测阳性的患者还给予化疗。3 年累积复发率、无白血病生存率和移植后生存率分别为 32.4%（95%可信区间，22.4%至 42.4%）、50.3%（95%可信区间，40.3%至 60.3%）和 51.4%（95%可信区间，41.2%至 61.6%）。多变量分析显示，MRD 检测阳性（HR，3.840；95%可信区间，1.678 至 5.784；P=0.001）和接受 1 疗程 DLI（HR，4.346；95%可信区间，1.223 至 9.450，P=0.023）与复发风险增加相关。这些数据表明，难治/复发急性白血病患者接受 allo-HSCT 后，预防性 DLI 继以 MRD 检测和 GVHD 指导的多次 DLI 可降低复发率，提高移植后生存率。该研究在 www.ClinicalTrials.gov 注册，编号为 NCT01455272。
