Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands.
Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, The Netherlands.
Bone Marrow Transplant. 2014 Feb;49(2):287-91. doi: 10.1038/bmt.2013.111. Epub 2013 Aug 12.
The prognosis of adult patients with ALL remains unsatisfactory. AlloSCT is associated with a beneficial GVL response mediated by donor T cells. However, GVHD results in substantial mortality and long-term morbidity. T-cell depletion (TCD) of the graft reduces the severity of GVHD, but is associated with an increased relapse rate after alloSCT. Therefore, early sequential donor lymphocyte infusion (DLI) is likely to be necessary for a successful GVL reaction. Twenty-five adult ALL patients (10 Ph(+)ALL) were eligible for early DLI after initial disease control with myeloablative TCD-alloSCT in first CR (CR1), if active GVHD was absent at 3-6 months after alloSCT. Patients with a sibling donor or an unrelated donor were scheduled for 3.0 × 10(6) CD3(+) cells/kg or 1.5 × 10(6) CD3(+) cells/kg, respectively, at 6 months after alloSCT. Three patients died before evaluation (one early relapse). Five patients had active GVHD. Fourteen of the remaining seventeen patients received DLI (median time-to-DLI: 185 days). Overall, only 17% required long-term systemic immunosuppression for GVHD. With a median follow-up after TCD-alloSCT of 50 months, 2-year survival probability was 68% (95% confidence interval (CI) 49-87%). In conclusion, myeloablative TCD-alloSCT with early sequential DLI is an efficient and safe post-remission treatment for adult ALL patients in CR1.
成人 ALL 患者的预后仍然不理想。AlloSCT 与供体 T 细胞介导的有益 GVL 反应相关。然而,GVHD 导致大量死亡和长期发病。移植物中 T 细胞的耗竭(TCD)可降低 GVHD 的严重程度,但与 alloSCT 后复发率增加相关。因此,对于成功的 GVL 反应,早期序贯供者淋巴细胞输注(DLI)可能是必要的。25 例成人 ALL 患者(10 例 Ph(+)ALL)在首次完全缓解(CR1)时接受清髓性 TCD-alloSCT 初始疾病控制后符合早期 DLI 的条件,如果 alloSCT 后 3-6 个月无活动性 GVHD。有同胞供体或无关供体的患者分别计划在 alloSCT 后 6 个月时给予 3.0×10(6) CD3(+)细胞/kg 或 1.5×10(6) CD3(+)细胞/kg。3 例患者在评估前死亡(1 例早期复发)。5 例患者有活动性 GVHD。其余 17 例患者中的 14 例接受了 DLI(DLI 的中位时间:185 天)。总体而言,只有 17%的患者因 GVHD 需要长期系统免疫抑制。在 TCD-alloSCT 后中位随访 50 个月时,2 年生存率为 68%(95%置信区间 49-87%)。总之,清髓性 TCD-alloSCT 联合早期序贯 DLI 是 CR1 成人 ALL 患者缓解后高效、安全的治疗方法。