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自体干细胞移植治疗滤泡性淋巴瘤:无论移植前是否使用利妥昔单抗,均有良好的长期生存获益。

Autologous Stem Cell Transplantation for Follicular Lymphoma: Favorable Long-Term Survival Irrespective of Pretransplantation Rituximab Exposure.

机构信息

Hospital Universitario 12 de Octubre, Madrid, Spain.

Hospital Universitario 12 de Octubre, Madrid, Spain.

出版信息

Biol Blood Marrow Transplant. 2017 Oct;23(10):1631-1640. doi: 10.1016/j.bbmt.2017.05.021. Epub 2017 May 19.

Abstract

High-dose chemotherapy supported by autologous stem cell transplantation (HDT/ASCT) has contributed to modify the natural history of follicular lymphoma (FL); however, an overall survival (OS) benefit has been demonstrated at relapse only after a rituximab-free chemotherapy regimen. A total of 655 patients with FL were reported to the Spanish GELTAMO (Grupo Español de Linfomas y Trasplantes de Médula Ósea) registry and underwent first ASCT between 1989 and 2007. A total of 203 patients underwent ASCT in first complete response (CR1), 174 in second complete response (CR2), 28 in third complete response (CR3), 140 in first partial response (PR1), 81 in subsequent PR, and 29 with resistant/refractory disease; 184 patients received rituximab before ASCT. With a median follow-up of 12 years from ASCT, median progression-free survival (PFS) and overall survival (OS) were 9.7 and 21.3 years, respectively. Actuarial 12-year PFS and OS were 63% (95% confidence interval [CI], 58%-68%) and 73% (95% CI, 68%-78%), respectively, for patients in CR (with a plateau in the curve beyond 15.9 years), 25% (95% CI, 19%-28%) and 49% (95% CI 42%-56%), respectively, for patients in PR, and 23% (95% CI, 8%-48%) and 28% (95% CI, 9%-45%), respectively, for patients with resistant/refractory disease (P < .001). In patients who received rituximab before ASCT, the estimated 9-year PFS and OS from ASCT were 59.5% (95% CI, 51%-67%) and 75% (95% CI, 68%-83%), respectively. Interestingly, for patients who underwent transplantation in CR ≥2 or PR ≥2 who had received rituximab before ASCT (n = 90), 9-year PFS and OS were 61% (95% CI, 51%-73%) and 75% (95% CI, 65%-80%), respectively, with no relapses occurring beyond 5.1 years after ASCT. The cumulative incidence of second malignancies in the global series was 6.7% at 5 years and 12.8% at 10 years. This analysis strongly suggests that ASCT is a potentially curative option for eligible patients with FL. In the setting of relapse, it is of especial interest in pretransplantation rituximab-sensitive patients with FL.

摘要

高剂量化疗联合自体干细胞移植(HDT/ASCT)有助于改变滤泡性淋巴瘤(FL)的自然病程;然而,仅在接受利妥昔单抗治疗后,无化疗方案的缓解才显示出总生存(OS)获益。西班牙 GELTAMO(Grupo Español de Linfomas y Trasplantes de Médula Ósea)登记处报告了 655 例 FL 患者,他们在 1989 年至 2007 年间接受了首次 ASCT。共有 203 例患者在首次完全缓解(CR1)时接受 ASCT,174 例在第二次完全缓解(CR2)时接受 ASCT,28 例在第三次完全缓解(CR3)时接受 ASCT,140 例在首次部分缓解(PR1)时接受 ASCT,81 例在随后的部分缓解时接受 ASCT,29 例患者耐药/难治;184 例患者在 ASCT 前接受了利妥昔单抗治疗。ASCT 后中位随访 12 年,无进展生存(PFS)和总生存(OS)的中位时间分别为 9.7 年和 21.3 年。对于 CR 患者(曲线在 15.9 年之后达到平台),12 年时的估计 PFS 和 OS 分别为 63%(95%CI,58%-68%)和 73%(95%CI,68%-78%),对于 PR 患者,分别为 25%(95%CI,19%-28%)和 49%(95%CI 42%-56%),对于耐药/难治患者,分别为 23%(95%CI,8%-48%)和 28%(95%CI,9%-45%)(P<0.001)。在接受 ASCT 前接受利妥昔单抗治疗的患者中,从 ASCT 开始的估计 9 年 PFS 和 OS 分别为 59.5%(95%CI,51%-67%)和 75%(95%CI,68%-83%)。有趣的是,对于在 CR≥2 或 PR≥2 且接受过 ASCT 前利妥昔单抗治疗的患者(n=90),9 年 PFS 和 OS 分别为 61%(95%CI,51%-73%)和 75%(95%CI,65%-80%),ASCT 后 5.1 年以上无复发。在全球系列中,5 年时的二次恶性肿瘤累积发生率为 6.7%,10 年时为 12.8%。这项分析强烈表明,ASCT 是适合 FL 患者的潜在治愈选择。在缓解时,对于接受移植前利妥昔单抗敏感的 FL 患者,这一点尤其有趣。

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