Table 1.
SCT studies and effect on ILD.
| Studies (N) | Regimen | Effect on lung function | Effect on HRCT | |
|---|---|---|---|---|
| FVC | DLco | |||
|
ASSIST28 n = 10 (SCT) (70%*) n = 9 (CYC) (89%*) Mean FU: 2.6 years Primary outcome: improvement at 12 months |
Mobilisation: CYC 2 g/m2, G-CSF Conditioning: CYC (200 mg/kg), rabbit ATG CD34 selection: no Comparator; CYC i.v. 6 months |
Baseline (median): SCT: 62% (range 53–70) CYC: 67% (range 43–84) Median change in 1 year: SCT: +20% CYC: −9% |
Baseline (median): SCT: 58% (range 29–82) CYC: 75% (range 29–111) Median change in 1 year: SCT: +9% CYC: −7% |
Baseline (ILD on scan): SCT: 70% CYC: 89% Change at 2 years: extent of ILD decreased after SCT but increased in controls |
|
ASTIS29
n = 79 (SCT) (86%*) n = 77 (CYC) (86%*) Median FU: 5.8 years Primary outcome: EFS at 24 months |
Mobilisation: CYC 4 g/m2, G-CSF Conditioning: CYC (200 mg/kg), rabbit ATG CD34 selection: yes Comparator; CYC i.v. 6 months |
Baseline (mean): SCT: 82% (SD 19) CYC: 81% (SD 18) Mean change in 2 years SCT: +6.3% (SD 18.3) CYC: −2.8 (SD 17.2) |
Baseline (mean):
SCT: 59% (SD 14) CYC: 58% (SD 14) Mean change in 2 years SCT: −4.7% (SD 13.7) CYC: −4.1 (SD 17.6) |
Baseline (ILD on scan): SCT: 87% CYC: 80% |
|
SCOT30 n= 36 (SCT) (100%*) n = 39 (CYC) (100%*) Mean FU: 54 months Primary outcome: GRCS at 54 months |
Mobilisation: G-CSF Conditioning: CYC (120 mg/kg), equine ATG TBI (800 cGy) CD34 selection: yes Comparator; CYC i.v. 6 months |
Baseline (mean): SCT: 74% (SD 15) CYC: 74% (SD 17) Change ITT group at 54 months: SCT n = 13 improvement** n = 10 no change n = 4 worsening** CYC n = 7 improvement n = 6 no change n = 8 worsening |
Baseline (mean): SCT: 54% (SD 8) CYC: 53% (SD 8) Change ITT group at 54 months: SCT n = 4 improvement*** n = 19 no change n = 13 worsening*** CYC n = 5 improvement n = 10 no change n = 24 worsening |
Baseline (ILD on scan): SCT: 100% CYC: 95% Change at 54 months:36 SCT Decreased ILD scores Stable fibrosis CYC No change ILD score Increased fibrosis |
|
Nash et al.34 N = 34 (79%*) Median follow-up 4 (range 1–6) years Primary outcome: improvement of mRSS and HAQ-DI |
Mobilisation: G-CSF
Conditioning: TBI (800 cGY), CYC (120 mg/kg), and equine ATG (90 mg/kg) CD34 selection: yes Comparator; none |
Baseline (median): 71 (range 27–103)
Mean change in 4 years +2.1% [95% CI −5.2 to 9.3, (p = 0.560)] +1.7 per year (95% CI 0.4–3.0, p = 0.010) |
Baseline (median): 62 (range 40–83) Mean change in 4 years −2.3% (95% CI −9.9 to 4.9, p = 0.310) +0.4 per year (95% CI 1.4–0.7, p = 0.50) |
Baseline HRCT (n = 34): Normal: 21% Ground-glass: 35% Fibrosis: 74% Change: 18%: ILD reactivation 18%: decreased ground-glass, increased fibrosis |
|
Bijnen et al.37 N = 92 (36%*) Median FU: 5 years (IQR 2–12 years) Primary outcome: EFS |
Mobilisation: CYC 2–4 g/m2, G-CSF Conditioning: CYC (200 mg/kg), rabbit ATG CD34 selection: yes Comparator; none |
Baseline (median, n = 66): 84% (range 68–102%) Median at 5 years (n = 40) 94% (range 81–107) +2.5 (1.9–3.0) per year |
Baseline (median, n = 67): 55% (range 42–67%) Median at 5 years (n = 38) 61% (range 53–73) +1.6 (1.0–2.2) per year |
Median Goh scores Baseline (median, n = 39) 14% (range 7–34%) At 5 years (median, n = 16) 8% (range 3–23%) −1.0 (−1.9 to 0.0) per year |
|
Henes et al.25 N = 80 (86%*) FU: 2 years Primary outcome: PFS at 2 years |
Mobilisation: CYC 1–4 g/m2, G-CSF Conditioning: CYC (50–240 mg/kg), rabbit ATG, thiotepa 10 mg/kg CD34 selection: both Comparator; none |
Baseline (mean, n = 37) 74% (SD 16.9) Mean at 1 year: 80% (SD 17) Mean at 2 years: 81% (SD 19) |
Baseline (mean, n = 35) 60% (SD 19.3) Mean at 1 year: 60% (SD 18) Mean at 2 year: 60% (SD 19) |
– |
|
Henrique-Neto et al.32 N = 70 (84%*) FU: 8 years Primary outcome: – |
Mobilisation: CYC 2 g/m2, G-CSF Conditioning: 200 mg/kg CYC and 4.5 mg/kg ATG CD34 selection: yes Comparator; none |
Baseline (median, n = 70): 70 (range 35–122) n = 66 stabilisation Median at 5 years (n = 51) 75% (range 48–110, p = 0.020) |
Baseline (median, n = 70): 70 (range 48–125) n = 66 stabilisation Change at 5 years (n = 51) 76% (range 50–115, p = 0.030) |
– |
|
Farge et al.33 N = 57 (57%*) FU: 36 months |
Mobilisation: CYC 4 g/m2, +/−G-CSF Conditioning: CYC (150–200 mg/kg), other chemotherapy, rabbit ATG, TBI CD34 selection: both Comparator; none |
Baseline (n = 47): 57% had FVC <70% No significant change during 36 months of FU |
Baseline (n = 47): 64% had DLco <70% No significant change during 36 months of FU |
|
|
Del Papa et al.35 N = 18 (67%*) FU: 60 months Primary outcome: – |
Mobilisation: CYC 4 g/m2, G-CSF Conditioning: CYC (200 mg/kg), rabbit ATG CD34 selection: yes |
Baseline (median): 68% (range 51–100) Median at 60 months 62% (range 30–85) |
– | |
*
Percentage of patients with ILD.
**
⩾10%.
***
⩾15%
ASSIST, American Scleroderma Stem Cell versus Immune Suppression Trial; ASTIS, Autologous Stem Cell Transplantation International Scleroderma; ATG, anti-thymocyte globulin; CI, confidence interval; CYC, cyclophosphamide; DLco, diffusing capacity of the lungs for carbon monoxide; EFS, event free survival; FU, follow-up; FVC, forced vital capacity; G-CSF, granulocyte colony-stimulating factor; GRCS, global rank composite scores; HAQ-DI, Health Assessment Questionnaire-Disability Index; HRCT, high resolution computed tomography; ILD, interstitial lung disease; IQR, interquartile range; ITT, intention-to-treat; i.v., intravenous; mRSS, modified Rodnan skin score; PFS, progression-free survival; SCOT, Scleroderma: Cyclophosphamide Or Transplantation; SCT, stem cell transplantation; SD, standard deviation; TBI, total body irradiation.