Transplant Program, Hematology Department, Paoli Calmettes Institute, Marseille, France.
Cancer. 2013 Feb 1;119(3):602-11. doi: 10.1002/cncr.27786. Epub 2012 Aug 14.
The optimal intensity of reduced-intensity conditioning (RIC) before allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains uncertain.
In this centrally randomized phase 2 study, the authors compared 2 different strategies of RIC. In total, 139 patients (median age, 54 years; range, 21-65 years) with hematologic malignancies underwent allo-HSCT from a human leukocyte antigen-identical sibling after conditioning combining fludarabine with either busulfan and rabbit antithymocyte-globulin (BU-rATG) (n = 69) or total body irradiation (TBI) (n = 70). Postgraft immunosuppression consisted of cyclosporin A in all patients with the addition of mycophenolate-mophetil after TBI.
The median follow-up was 54 months (range, 26-88 months). One-year overall survival rate was identical in both groups. Four patients experienced graft-failure after TBI. The incidence of grade 2 through 4 acute graft-versus-host-disease was greater after BU-rATG than after TBI (47% vs 27%; P = .01), whereas no difference was observed with chronic graft-versus-host-disease. The BU-rATG group had a higher objective response rate (65% vs 46%; P = .05) and a lower relapse rate (27% vs 54%; P < .01). However, the nonrelapse mortality rate was higher after BU-rATG than after TBI (38% vs 22%; P = .027). At 5 years, the overall and progression-free survival rates were 41% and 29%, respectively, and did not differ statistically between groups. A detrimental effect on some parameters of quality of life was more pronounced after BU-rATG, but recovery was identical in both groups. The mean total cost per patient, including the cost to treat disease progression post-transplantation, did not differ statistically between groups.
Five years after transplantation, the BU-rATG regimen was associated with greater disease control. However, because of the higher nonrelapse mortality rate, this did not translate into better overall or progression-free survival.
异基因造血干细胞移植（allo-HSCT）前，降低强度的预处理（RIC）的最佳强度仍不确定。
在这项中心随机的 2 期研究中，作者比较了两种不同的 RIC 策略。共有 139 例血液系统恶性肿瘤患者（中位年龄 54 岁，范围 21-65 岁），在接受含氟达拉滨的预处理后，接受 HLA 完全匹配的同胞供者 allo-HSCT，预处理方案分别为马利兰和兔抗胸腺细胞球蛋白（BU-rATG）（n=69）或全身照射（TBI）（n=70）。移植后免疫抑制方案均为环孢素 A，TBI 后加用霉酚酸酯。
中位随访时间为 54 个月（范围 26-88 个月）。两组患者 1 年总生存率相同。4 例患者在 TBI 后发生移植物失败。BU-rATG 组 2-4 级急性移植物抗宿主病发生率高于 TBI 组（47% vs 27%；P=.01），而慢性移植物抗宿主病发生率无差异。BU-rATG 组客观缓解率更高（65% vs 46%；P=.05），复发率更低（27% vs 54%；P<.01）。然而，BU-rATG 组非复发死亡率高于 TBI 组（38% vs 22%；P=.027）。5 年时，总生存率和无进展生存率分别为 41%和 29%，两组间无统计学差异。BU-rATG 组生活质量某些参数的不良影响更为明显，但两组恢复情况相同。包括移植后疾病进展治疗费用在内的每位患者的总费用在两组间无统计学差异。
移植后 5 年，BU-rATG 方案与更好的疾病控制相关。然而，由于非复发死亡率较高，这并未转化为更好的总生存率或无进展生存率。
