Randomised controlled trials of autologous HSCT in autoimmune diseases
| Disease | Trial | Number of patients | Mobilisation regimen | Conditioning regimen | Comparator arm | Results | Reference (number) |
|---|---|---|---|---|---|---|---|
| MS | ASTIMS | 21 | Cy 4 g/m2 + G-CSF | BEAM + rATG | Mitoxantrone + methylprednisolone
monthly for 6 months | aHSCT significantly superior to mitoxantrone in reducing MRI activity in severe MS (79% reduction in T2 lesions). No difference in disease progression. No TRM | 12 |
| MS | MIST | 110
Interim analysis | Cy 2 g/m2 + G-CSF | Cy 200 mg/kg + rATG | Standard of DMT care (interferons, glatiramer acetate, dimethyl fumarate, fingolimod, natalizumab, but not alemtuzumab), | aHSCT statistically superior to continued DMTs in terms of disability scores (EDSS) and progression in patients with RRMS with >2 relapses a year. No TRM | 13 |
| SSc | ASSIST | 19 | Cy 2g/m2 + G-CSF | Cy 200 mg/kg + rATG | Cy 1 g/m2 monthly for 6 months | All aHSCT (10/10) patients improved in skin score and lung function at 12 months compared to 0/9 in control. No TRM | 14 |
| SSc | ASTIS | 156 | Cy 4 g/m2 + G-CSF | Cy 200 mg/kg + rATG | Cy 750 mg/m2
monthly for 12 months | EFS and OS favoured aHSCT at 5.8 years. TRM 10% | 15 |
| SSc | SCOT | 75 | G-CSF | Cy 200 mg/kg + hATG + TBI 800 cGy (with lung and kidney shielding) | Cy 500 mg/m2 for 1 month, then 750 mg/m2 for 11 months | Superiority of aHSCT for GRCS (at 54 months), and EFS and OS (at 72 months). TRM 3% at 54 months and 6% at 72 months. Three malignancies in aHSCT group (possibly TBI related) compared with one in control group | 16 |
| CD | ASTIC | 45 | Cy 4 g/m2 + G-CSF | Cy 200 mg/kg + rATG | Early versus late aHSCT | Failed primary endpoint (sustained clinical remission off medication with no evidence of active disease on endoscopy or imaging). TRM in 1 patient | 18 |
| CD | ASTIC secondary analysis | 38 | Cy 4 g/m2 + G-CSF | Cy 200 mg/kg + rATG | Open label cohort of all patients undergoing aHSCT in ASTIC trial | 3 months steroid-free remission at 1 year: 38%, 95% CI 22–55. Complete endoscopic healing: 50%, 95% CI 34–66 | 19 |
ASSIST = American Scleroderma Stem Cell versus Immune Suppression Trial; ASTIC = Autologous Stem Cell Transplantation International Crohn's disease; ASTIMS = Autologous Stem Cell Transplantation International MS; ASTIS = Autologous Stem Cell Transplantation International Scleroderma; BEAM = BCNU/Etoposide/ARA-C/Melphalan; Cy = cyclophosphamide; EDSS = expanded disability status scale; EFS = event-free survival; G-CSF = granulocyte colony-stimulating factor; GRCS = global rank composite score; hATG = horse antithymocyte globulin; MIST = Multiple Sclerosis International Stem cell Transplant trial; OS = overall survival; rATG = rabbit antithymocyte globulin; SCOT = Scleroderma: Cyclophosphamide or Transplantation; TBI = total body irradiation; TRM = transplant-related mortality