Drs. Khanna, Clements Summarize Four Scleroderma Studies Presented at Medical Conference

Philip Clements, M.D. and Dinesh Khanna, M.D.

Below is a summary of four scleroderma studies presented at the annual American College of Rheumatology meeting last month.

Dinesh Khanna, M.D., and Philip Clements, M.D., moderators of "Systemic Sclerosis: An Update on Stem Cell Transplantation"

"Autologous non-myeloablative Peripheral Blood Stem Cell Transplantation in Patients with Systemic Sclerosis." Barr et al.

In this preliminary 10 patient report, systemic scleroderma patients (SSc) patients were treated with a regimen of cyclophosphamide (cytoxan) and bone marrow stimulant followed by rabbit anti-thymocyte globulin (to increase immunosuppression) for their systemic sclerosis. This is the same myeloablative regimen (the Europeans call this regimen myeloablative), which is being used in Europe as part of the ASTIS multicenter trial. Patient entrance criteria required a skin score (measure of skin thickness) and presence of scleroderma lung disease, elevated ESR, renal involvement, or abnormal electrocardiogram. Skin improved and pulmonary function remained relatively stable. Functional disability was not measured. Encouragingly, there were no transplant related deaths but three out of the ten patients relapsed (2) or died from progression (1). Apparently, the relapses were stabilized with use of mycophenolate mofetil. In this abstract, the two-year "event free" survival (survival without mortality, relapse or progression of SSc, resulting in major organ dysfunction) was 70%. This myeloablative regimen, not including radiation, deserves further study, as is being done in Europe.

"High Dose Cyclophosphamide Without Stem Cell Transplantation in Systemic Sclerosis." Tehlirian et al.

In an early study of four patients with severe SSc, high dose cyclophosphamide (200mg/kg) plus bone marrow stimulant were used. No myeloablative regimen or radiation was used. Out of the four patients, three patients improved their skin and daily function while pulmonary function remained stable. One of the four patients died secondary to infection and one patient relapsed after about 12 months. While very early data, "event free" survival was 50% by one year. More patients need to be tested with this particular regimen before any conclusions are reached.

"Marked Improvement in Skin and Overall Function in High-Risk Patients with Severe Systemic Sclerosis (SSc) Who Underwent High-Dose Immunosuppressive Therapy (HDIT) and Stem Cell Transplantation." Nash et al.

Dr. Richard Nash and colleagues presented results of a pilot study in which 34 patients with severe SSc and internal organ involvement underwent HDIT regimen and radiation. In this study, HDIT includes a high dose of chemotherapy with cyclophosphamide, anti-thymocyte globulin, and low dose total body irradiation (TBI). The TBI increased the necessary immunosuppression and has been safe thus far in SSc and was the major difference compared to Barr abstract. Results revealed significant improvements in SSc and in physical function persisting at eight years post transplant. Skin scores showed marked improvement and skin biopsies revealed normalization of tissue. Lung, heart, and kidney function remained stable. The survival rate was 64% at five years. From this pilot study, researchers instituted changes to the transplant regimen to improve outcome. Using these design modifications, survival in the pilot study patients eligible for Scleroderma: Cyclophosphamide or Transplantation (SCOT) was 91% at three years. SCOT is a NIH-sponsored, multicenter, randomized clinical trial comparing HDIT and transplant to monthly cyclophosphamide.

"Long-Term Follow-Up Results After Autologous Hematopoietic Stem Cell Transplantation for Severe Systemic Sclerosis." Vonk et al.

Twenty-six patients were entered: patients with diffuse SSc of less than two years duration and SSc patients with longer duration of SSc who had increasing skin thickening and worsening organ involvement. They underwent stem cell stimulation with cyclophosphamide 4 gram/m2 and bone marrow stimulant. No rabbit anti-thymocyte globulin was given. After stem cells were harvested, patients received a myeloablative dose of 200 mg/kg of CYC. Stem cells were then infused.

After a median follow-up of 5.3 years, 81% had demonstrated a positive response. The Kaplan-Meier survival curve predicted seven-year survival of 85% and event-free survival at seven years was 57%. A significant improvement in functional performance and in skin score was noted at six months and continued throughout follow-up. Lung, kidney, and heart function remained stable.