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

Br J Haematol. 2002 Dec;119(3):726-39. doi: 10.1046/j.1365-2141.2002.03895.x.


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/m2) and recombinant human granulocyte colony-stimulating factor (5 micro g/kg/d) and reinfused after positive CD34+ selection. Conditioning used cyclophosphamide (200 mg/kg) or melphalan (140 mg/m2) 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.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Agents, Alkylating / therapeutic use
  • Bone Marrow Transplantation / methods*
  • CD4-Positive T-Lymphocytes / transplantation
  • Cyclophosphamide / therapeutic use
  • Feasibility Studies
  • Female
  • Follow-Up Studies
  • Graft Survival
  • Granulocyte Colony-Stimulating Factor / therapeutic use
  • Hematopoietic Stem Cell Mobilization / adverse effects
  • Hematopoietic Stem Cell Mobilization / methods
  • Hematopoietic Stem Cell Transplantation / adverse effects
  • Hematopoietic Stem Cell Transplantation / methods*
  • Humans
  • Immunomagnetic Separation
  • Immunosuppressive Agents / therapeutic use
  • Lymphocyte Depletion / methods
  • Male
  • Melphalan / therapeutic use
  • Middle Aged
  • Recurrence
  • Scleroderma, Systemic / therapy*
  • Survival Analysis
  • Transplantation, Autologous
  • Treatment Failure


  • Antineoplastic Agents, Alkylating
  • Immunosuppressive Agents
  • Granulocyte Colony-Stimulating Factor
  • Cyclophosphamide
  • Melphalan