title: Autologous bone marrow transplantation in the treatment of refractory systemic sclerosis: early results from a French multicentre phase I-II study.
abstract: 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.
authors.affiliation: Service de Médecine Interne, site transfusionnel de Saint-Louis, France. dominique.farge-bancel@sls.ap-hop-paris.fr
authors.forename: Dominique
authors.initials: D
authors.lastname: Farge
authors.forename: Jean Pierre
authors.initials: JP
authors.lastname: Marolleau
authors.forename: Sarah
authors.initials: S
authors.lastname: Zohar
authors.forename: Zora
authors.initials: Z
authors.lastname: Marjanovic
authors.forename: Jean
authors.initials: J
authors.lastname: Cabane
authors.forename: Nicolas
authors.initials: N
authors.lastname: Mounier
authors.forename: Eric
authors.initials: E
authors.lastname: Hachulla
authors.forename: Pierre
authors.initials: P
authors.lastname: Philippe
authors.forename: Jean
authors.initials: J
authors.lastname: Sibilia
authors.forename: Claire
authors.initials: C
authors.lastname: Rabian
authors.forename: Sylvie
authors.initials: S
authors.lastname: Chevret
authors.forename: Eliane
authors.initials: E
authors.lastname: Gluckman
mesh_terms: D000293:Adolescent; D000328:Adult; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D016026:Bone Marrow Transplantation / Q000379:methods*; D015496:CD4-Positive T-Lymphocytes / Q000637:transplantation; D003520:Cyclophosphamide / Q000627:therapeutic use; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006085:Graft Survival; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D019650:Hematopoietic Stem Cell Mobilization / Q000009:adverse effects / Q000379:methods; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D018189:Immunomagnetic Separation; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008212:Lymphocyte Depletion / Q000379:methods; D008297:Male; D008558:Melphalan / Q000627:therapeutic use; D008875:Middle Aged; D012008:Recurrence; D012595:Scleroderma, Systemic / Q000628:therapy*; D016019:Survival Analysis; D014182:Transplantation, Autologous; D017211:Treatment Failure
chemical_list: D018906:Antineoplastic Agents, Alkylating; D007166:Immunosuppressive Agents; D016179:Granulocyte Colony-Stimulating Factor; D003520:Cyclophosphamide; D008558:Melphalan