Department and CIC, CHU Hotel Dieu, Nantes, France.
Biol Blood Marrow Transplant. 2013 Jun;19(6):934-9. doi: 10.1016/j.bbmt.2013.03.009. Epub 2013 Mar 21.
Recent advances in allogeneic stem cell transplantation (allo-HSCT) have included the advent of reduced-intensity conditioning (RIC) regimens to decrease the toxicity of myeloablative allo-SCT and the use of double umbilical cord blood (dUCB) units as a graft source in adults lacking a suitable donor. The FB2A2 regimen (fludarabine 30 mg/kg/day for 5-6 days + i.v. busulfan 3.6 mg/kg/day for 2 days + rabbit antithymocyte globulin 2.5 mg/kg/day for 2 days) supported by peripheral blood stem cells (PBSCs) and the TCF regimen (fludarabine 200 mg/m² for 5 days + cyclophosphamide 50 mg/kg for 1 day + low-dose [2 Gy] total body irradiation) supported by dUCB units are currently the most widely used RIC regimens in many centers and could be considered standard of care in adults eligible for an RIC allo-SCT. Here we compared, retrospectively, the outcomes of adults patients who received the FB2A2-PBSC RIC regimen (n = 52; median age, 59 years; median follow-up, 19 months) and those who received the dUCB-TCF RIC regimen (n = 39; median age, 56 years; median follow-up, 20 months) for allo-SCT between January 2007 and November 2010. There were no significant between-group differences in patient and disease characteristics. Cumulative incidences of engraftment, acute grade II-IV and chronic graft-versus-host disease were similar in the 2 groups. The median time to platelet recovery, incidence of early death (before day +100), and 2-year nonrelapse mortality were significantly higher in the dUCB-TCF group (38 days versus 0 days [P <.0001]; 20.5% versus 4% [P = .05], and 26.5% versus 6% [P = .02], respectively). The groups did not differ in terms of 2-year overall survival (62% for FB2A2-PBSC versus 61% for dUCB-TCF), disease-free survival (59% versus 50.5%), or relapse incidence (35.5% versus 23%). In multivariate analysis, the presence of a lymphoid disorder was associated with a significantly higher 2-year overall survival (hazard ratio, 0.42; 95% confidence interval, 0.20-0.87; P = .02), whereas patients receiving a FB2A2-PBSC allo-SCT had a significantly lower 2-year nonrelapse mortality (hazard ratio, 0.24; 95% confidence interval, 0.1-0.7; P = .01). There were no factors associated with higher 2-year disease-free survival or lower relapse incidence. This study suggests that the dUCB-TCF regimen provides a valid alternative in adults lacking a suitable donor and eligible for RIC allo-SCT. Prospective and randomized studies are warranted to establish the definitive role of dUCB RIC allo-SCT in adults. In addition, strategies for decreasing nonrelapse mortality after dUCB RIC allo-SCT are urgently needed.
最近异体造血干细胞移植（allo-HSCT）的进展包括出现了降低强度的预处理（RIC）方案，以降低骨髓清除性 allo-SCT 的毒性，以及使用双脐血（dUCB）单位作为缺乏合适供体的成人的移植物来源。FB2A2 方案（氟达拉滨 30mg/kg/天，连用 5-6 天+静脉用白消安 3.6mg/kg/天，连用 2 天+兔抗胸腺细胞球蛋白 2.5mg/kg/天，连用 2 天）联合外周血干细胞（PBSCs）和 TCF 方案（氟达拉滨 200mg/m²，连用 5 天+环磷酰胺 50mg/kg，连用 1 天+低剂量[2Gy]全身照射）联合 dUCB 单位是目前许多中心最广泛使用的 RIC 方案，可被认为是适合 RIC allo-SCT 的成人的标准治疗方法。在此，我们回顾性比较了 2007 年 1 月至 2010 年 11 月期间接受 FB2A2-PBSC RIC 方案（n=52；中位年龄 59 岁；中位随访时间 19 个月）和接受 dUCB-TCF RIC 方案（n=39；中位年龄 56 岁；中位随访时间 20 个月）allo-SCT 的成人患者的结局。两组患者和疾病特征无显著差异。两组间植入、急性 II-IV 级和慢性移植物抗宿主病的累积发生率相似。dUCB-TCF 组血小板恢复的中位时间、早期死亡（+100 天前）的发生率和 2 年非复发死亡率显著较高（38 天与 0 天[P<.0001]；20.5%与 4%[P=.05]，26.5%与 6%[P=.02]）。两组在 2 年总生存率（FB2A2-PBSC 为 62%，dUCB-TCF 为 61%）、无病生存率（59%与 50.5%）或复发率（35.5%与 23%）方面无差异。多变量分析显示，存在淋巴细胞疾病与 2 年总生存率显著相关（危险比，0.42；95%置信区间，0.20-0.87；P=0.02），而接受 FB2A2-PBSC allo-SCT 的患者 2 年非复发死亡率显著较低（危险比，0.24；95%置信区间，0.1-0.7；P=0.01）。没有与更高的 2 年无病生存率或更低的复发率相关的因素。本研究表明，dUCB-TCF 方案为缺乏合适供体且适合 RIC allo-SCT 的成人提供了一种有效的替代方案。需要前瞻性和随机研究来确定 dUCB RIC allo-SCT 在成人中的明确作用。此外，迫切需要制定降低 dUCB RIC allo-SCT 后非复发死亡率的策略。
