Autologous bone marrow transplantation in the treatment of refractory systemic sclerosis: early results from a French multicentre phase I-II study

被引:100
作者
Farge, D
Marolleau, JP
Zohar, S
Marjanovic, Z
Cabane, J
Mounier, N
Hachulla, E
Philippe, P
Sibilia, J
Rabian, C
Chevret, S
Gluckman, E
机构
[1] Hop St Louis, Serv Med Interne, F-75010 Paris, France
[2] AP HP, Etab Transfus Sanguine, Paris, France
[3] AP HP, INSERM, U444, Dept Biostat & Med Informat, Paris, France
[4] Hop St Antoine, Serv Med Interne, F-75571 Paris, France
[5] Serv Oncohematol, Paris, France
[6] CHU Claude Huriez, Serv Med Interne, Lille, France
[7] Hop Hotel Dieu, Serv Med Interne, Clermont Ferrand, France
[8] Hop Haute Pierre, Serv Rhumatol, Strasbourg, France
[9] Hop St Louis, Lab Immunol Histocompatibil, Paris, France
[10] Hop St Louis, Serv Greffe Moelle, Paris, France
关键词
autologous bone marrow transplantation; systemic sclerosis; haematopoietic stem cell transplantation; CD34(+) cell selection; Bayesian method;
D O I
10.1046/j.1365-2141.2002.03895.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:726 / 739
页数:14
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