Department of Haematology, University College Hospital, London, UK.
J Clin Oncol. 2010 Aug 10;28(23):3695-700. doi: 10.1200/JCO.2009.26.9100. Epub 2010 Jul 6.
Follicular lymphoma (FL) is an indolent disorder that is treatable but considered incurable with chemotherapy alone. The curative potential of allogeneic transplantation using conventional myeloablative conditioning has been demonstrated, but this approach is precluded in the majority of patients with FL because of excessive toxicity. Thus, reduced-intensity conditioning regimens are being explored.
This study reports the outcome of 82 consecutive patients with FL who underwent transplantation using fludarabine, melphalan, and alemtuzumab for in vivo T-cell depletion. Patients were heavily pretreated, having received a median of four lines of prior therapy, and 26% had experienced treatment failure with previous autologous transplantation. Median patient age was 45 years, and 52% of patients received stem cells from unrelated donors.
With a median follow-up time of 43 months, the nonrelapse mortality was 15% at 4 years (8% for sibling and 22% for unrelated donor transplantations), acute grade 2 or 3 graft-versus-host disease (GVHD) occurred in 13%, and the incidence of extensive chronic GVHD was only 18%. Although relapse risk was 26%, this was significantly reduced where mixed chimerism had been converted to full donor chimerism by the use of donor lymphocyte infusion (DLI; P = .03). In addition, 10 (77%) of 13 patients given DLI for relapse after transplantation experienced remission, with nine of these responses being sustained. Current progression-free survival at 4 years was 76% for the whole cohort (90% for those with sibling donors and 64% for those with unrelated donors).
The excellent long-term survival with associated low rates of GVHD and the frequency and durability of DLI responses make this an extremely encouraging strategy for the treatment and potential cure of FL.
滤泡性淋巴瘤（FL）是一种惰性疾病，虽然可以通过化疗进行治疗，但单独使用化疗被认为无法治愈。使用常规清髓性预处理的异基因移植已显示出治愈潜能，但由于毒性过大，大多数 FL 患者无法采用这种方法。因此，正在探索减量化预处理方案。
本研究报告了 82 例连续 FL 患者接受氟达拉滨、美法仑和阿仑单抗进行体内 T 细胞耗竭后移植的结果。患者预处理程度较重，中位数接受了四线以上的既往治疗，26%的患者既往接受自体移植后治疗失败。中位患者年龄为 45 岁，52%的患者接受了无关供者的干细胞。
中位随访时间为 43 个月，4 年时非复发死亡率为 15%（同胞供者为 8%，无关供者为 22%），急性 2 或 3 级移植物抗宿主病（GVHD）发生率为 13%，广泛慢性 GVHD 的发生率仅为 18%。尽管复发风险为 26%，但使用供者淋巴细胞输注（DLI）将混合嵌合体转换为完全供者嵌合体可显著降低复发风险（P =.03）。此外，移植后因复发而接受 DLI 的 13 例患者中有 10 例（77%）获得缓解，其中 9 例缓解持续。整个队列的 4 年无进展生存率为 76%（同胞供者为 90%，无关供者为 64%）。
长期生存情况良好，GVHD 发生率低，DLI 反应的频率和持久性高，这使得该策略成为治疗和潜在治愈 FL 的极具前景的策略。
