Autologous bone marrow transplantation in the treatment of refractory systemic sclerosis: early results from a French multicentre phase I-II study
Autologous bone marrow transplantation in the treatment of refractory systemic sclerosis: early results from a French multicentre phase I-II study
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DOI：
10.1046/j.1365-2141.2002.03895.x
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发表时间：
2002-12-01
影响因子：
6.5
通讯作者：
Gluckman, E
中科院分区：
文献类型：
--
作者：
Farge, D;Marolleau, JP;Gluckman, E
造血干细胞移植（HSCT）已被提议用于难治性自身免疫性疾病，包括系统性硬化症（SSc）。在SSc患者中进行了序贯贝叶斯I-II期临床试验，以评估自体HSCT的可行性、耐受性和疗效。使用环磷酰胺（4 g/m2）和重组人粒细胞集落刺激因子（5 μ g/kg/d）收集外周血干细胞（PBSC），并在CD 34（+）选择阳性后回输。预处理根据心功能使用环磷酰胺（200 mg/kg）或美法仑（140 mg/m2）。主要终点是手术失败，定义为PBSC动员、CD 34（+）选择或强化手术失败，或手术相关死亡。在12例入组患者中，发生了3例失败：1例PBSC动员，1例CD 34（+）选择和1例CD 34（+）强化。移植物失效的概率估计为0.286（95%置信区间：0.095-0.54）。11例患者实际进行了自体PBSC（n = 10）或骨髓（n = 1）移植，其中1例手术相关死亡。中性粒细胞（> 0.5 × 10（9）/l）和血小板（> 25 × 10（9）/l）造血重建的中位时间分别为12天和10天。18个月后（范围1-26），11例患者中有8例显示出主要或部分缓解。非清髓性预处理，然后是T细胞耗尽的自体PBSC或骨髓移植，似乎是可行的，毒性低，在严重的SSc与短期的临床效益。
Haematopoietic stem cell transplantation (HSCT) has been proposed for refractory autoimmune diseases, including systemic sclerosis (SSc). A sequential Bayesian phase I-II clinical trial was conducted in SSc patients to assess the feasibility, the tolerance and the efficacy of autologous HSCT. Peripheral blood stem cells (PBSC) were collected using cyclophosphamide (4 g/m(2)) and recombinant human granulocyte colony-stimulating factor (5 mug/kg/d) and reinfused after positive CD34(+) selection. Conditioning used cyclophosphamide (200 mg/kg) or melphalan (140 mg/m(2)) according to cardiac function. The main end-point was the failure of the procedure, defined by failure of either PBSC mobilization, CD34(+) selection or intensification procedure, or by procedure-related death. Among the 12 enrolled patients, three failures occurred: one PBSC mobilization, one CD34(+) selection and one CD34(+) intensification. Probability of graft failure was estimated at 0.286 (95% confidence interval: 0.095-0.54). Autologous PBSC (n = 10) or bone marrow (n = 1) transplantation was actually performed in 11 patients with one procedure-related death. Median time to neutrophil (> 0.5 x 10(9)/l) and platelet (> 25 x 10(9)/l) haematopoietic reconstitution was 12 and 10 d respectively. After 18 months ( range 1-26), eight out of 11 patients have shown major or partial response. Non-myeloablative conditioning, followed by a T cell-depleted autologous PBSC or bone marrow transplantation, appears feasible with low toxicity in severe SSc with short-term clinical benefits.