Table 4 Autologous stem cell transplant studies in patients with systemic sclerosis
Trial | ASSIST [52] (2011) | ASTIS [51] (2014) | SCOT [50] (2018) | Del Papa et. al. [53] (2017) | NISSC1 [54] (2021) |
|---|---|---|---|---|---|
Biological effect of ASCT | Non-myeloablative | Lymphoablative | Myeloablative | Unspecified | Non- myeloablative |
Design | Single center, prospective, randomized | Multicenter, prospective, randomized | Multicenter, prospective, randomized | Single center, retrospective, observational | Multicenter, prospective, observational |
Inclusion criteria | Age < 60, cutaneous involvement proximal to elbow or knee with mRSS > 14, internal organ involvement (DLCO < 80%, decrease in FVC by ≥ 10% in 12 months, pulmonary fibrosis, abnormal ECG, or GI tract involvement) | Age 18–65, diffuse cutaneous SSc for < 4 years, mRSS > 14, cardiac, pulmonary, or renal involvement | Age 18–69 with SSc for ≤ 5 years with pulmonary or renal involvement | SSc for < 4 years, mRSS ≥ 14, European Scleroderma Study Group (ESSG) clinical activity score ≥ 3 | Age 18–65, established SSc, autologous HSCT |
ASCT participants | 10 | 79 | 36 | 18 | 80 |
Control participants | 9 | 77 | 39 | 36 | NA |
Total body irradiation | No | No | Yes | No | No |
CD34 + cell mobilization | CYC 2 g/m2 IV × 1 d plus G-CSF 10 µg/kg SC from day 5 post CYC until apheresis | CYC 4 g/m2 IV ~ 100 mg/Kg for 2 days G-CSF 10 µg/Kg/day | G-CSF 16 µg/kg/day for 4 days | CYC 4 g/m2 for 2 days and G-CSF 10 µg/kg | CYC 1–4 g/m2 and G-CSF, dose unspecified |
Conditioning regimen | CYC 200 mg/Kg IV plus mesna day − 5 to day − 2, ATG 0.5 mg/Kg IV day − 5, 1.5 mg/Kg day − 4 to day − 1 plus GC 1000 mg | CYC 200 mg/Kg IV for 4 days ATG 7.5 mg/Kg for 3 days GC 1 mg/Kg | CYC 120 mg/Kg IV plus mesna for days − 3 to − 2 and ATG 90 mg/Kg on days − 5, − 3, − 1, + 1, + 3, + 5 | CYC 200 mg/kg IV with mesna day − 5 to − 2 and ATG 7.5 mg/kg with GC IV 1 mg/kg day − 3 to − 1 | CYC 200 mg/kg IV (4 patients received thiotepa 10 mg/kg and CYC 100 mg/kg) ATG (varied dosing) ± GC at unspecified dose |
Controls | 1.0 g/m2 IV CYC plus mesna monthly for 6 mo | 750 mg/m2 IV CYC monthly for 12 mo | 500 mg/m2 IV CYC at baseline followed by 750 mg/m2 IV CYC and mesna for 11 mo | 1 g IV CYC monthly for ≥ 6 mo. plus 5–10 mg prednisone or MTX (10–20 mg w.) or AZA (100–200 mg/day), plus low-dose prednisone (5–10 mg/day), or pulse methylprednisolone followed by low-dose AZA, unspecified dose | Not applicable |
Primary outcome | mRSS decrease or FVC increase at 12 months after treatment randomization | Event-free survival, defined as the time in days from randomization until the occurrence of death due to any cause or development of persistent major organ failure—heart, lung, or kidney | Global rank composite score (ranking system that accounts for death, failure of event free survival, FVC, HAQ-DI, and mRSS) at 54 months | mRSS, DLco, and disease activity, according to European Scleroderma Study Group scoring system (ESSG) | Progression-free survival defined as survival after ASCT without death or progression of SSc |
Follow-up | 5 y | median 5.8 y | Up to 6 y | Up to 5 y | Median 2 y |
Results | All patients in HSCT group improved at, or before, 12 mo | Increased treatment-related mortality in first year, but long-term event-free survival benefit | Superiority in transplant group | Higher survival rate, reduced skin involvement and disease activity, and preservation of lung diffusing capacity in treatment group | Progression- free survival rate of 81.8% at 2 y |