Blood and Marrow Transplant Program, H. Lee Moffitt Cancer and Research Center, Tampa, Florida, USA.
Biol Blood Marrow Transplant. 2011 Jul;17(7):1051-7. doi: 10.1016/j.bbmt.2010.11.004. Epub 2010 Nov 10.
Patients with follicular lymphoma (FL) typically experience an indolent course; however, the disease is rarely curable with conventional chemotherapy. Autologous hematopoietic cell transplantation (HCT) can extend progression-free survival (PFS) and overall survival (OS), but relapse is the primary cause of failure. Allogeneic HCT confers lower relapse rates due to a graft-versus-lymphoma effect. Reduced-intensity conditioning (RIC) allows the performance of allogeneic HCT with lower toxicity. The Blood and Marrow Transplant Clinical Trials Network conducted a prospective multicenter trial comparing these two strategies in patients with relapsed, chemotherapy-sensitive FL. Patients were assigned to a treatment arm based on the availability of an HLA-matched sibling donor (MSD). Those with an MSD underwent allogeneic HCT (n = 8) with the FCR preparative regimen (fludarabine, cyclophosphamide [Cy], rituximab [RTX]) and received tacrolimus and methotrexate for graft-versus-host disease (GVHD) prophylaxis. Those without an MSD (n = 22) underwent mobilization with Cy, RTX, and filgrastim and received a conditioning regimen of either CBV (Cy, carmustine, Etoposide [VP16]) or total body irradiation with Cy and VP16. Patients undergoing autologous HCT received 4 doses of weekly maintenance RTX (375 mg/m²) starting on day +42 post-HCT. Sixteen patients were in complete remission, 10 patients were in partial remission, and 1 patient had stable disease after salvage therapy and before HCT. Median follow-up was 36 months (range, 1-51 months). OS was 73% in autologous HCT versus 100% in allogeneic HCT, and PFS was 63% in autologous HCT versus 86% in allogeneic HCT. No patient had grade II-IV acute GVHD; two patients developed extensive chronic GVHD. Three autologous recipients died from nonrelapse causes. This trial closed early because of slow accrual. We show that the FCR regimen is well tolerated, and that both allogeneic and autologous HCT result in promising 3-year OS and PFS in patients with relapsed FL.
滤泡性淋巴瘤 (FL) 患者通常表现为惰性病程;然而,常规化疗很少能治愈这种疾病。自体造血细胞移植 (HCT) 可以延长无进展生存期 (PFS) 和总生存期 (OS),但复发是失败的主要原因。异基因 HCT 由于移植物抗淋巴瘤效应而降低复发率。由于毒性较低,因此采用低强度预处理方案 (RIC) 进行异基因 HCT。血液和骨髓移植临床研究网络在复发的化疗敏感型 FL 患者中进行了一项比较这两种策略的前瞻性多中心试验。患者根据是否有 HLA 匹配的同胞供体 (MSD) 分配到治疗组。有 MSD 的患者接受异基因 HCT(n = 8),预处理方案为 FCR(氟达拉滨、环磷酰胺 [Cy]、利妥昔单抗 [RTX]),并接受他克莫司和甲氨蝶呤预防移植物抗宿主病 (GVHD)。没有 MSD 的患者(n = 22)接受 Cy、RTX 和非格司亭动员,并接受 CBV(Cy、卡莫司汀、依托泊苷 [VP16])或全身照射加 Cy 和 VP16 的预处理方案。接受自体 HCT 的患者在 HCT 后第 42 天开始接受每周 4 次维持性 RTX(375 mg/m²)。16 例患者在挽救治疗后和 HCT 前达到完全缓解,10 例患者达到部分缓解,1 例患者疾病稳定。中位随访时间为 36 个月(范围,1-51 个月)。自体 HCT 的 OS 为 73%,异基因 HCT 的 OS 为 100%,自体 HCT 的 PFS 为 63%,异基因 HCT 的 PFS 为 86%。没有患者发生 II-IV 级急性 GVHD;两名患者发生广泛的慢性 GVHD。3 名自体受者因非复发原因死亡。由于入组缓慢,该试验提前关闭。我们表明,FCR 方案具有良好的耐受性,并且在复发的 FL 患者中,异基因和自体 HCT 都能带来有希望的 3 年 OS 和 PFS。