Introduction
Methods
Study design and patients
Transplant procedure
Clinical follow-up before and after aHSCT
Immunomonitoring
T cell repertoire and clonality
Statistical analysis
Results
Patients clinical characteristics and response to aHSCT
Group A patients (n = 5) | Group B patients (n = 5) | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
1 | 2 | 3 | 4 | 5 | Mean (±SD) | 1 | 2 | 3 | 4 | 5 | Mean (±SD) | Mean (±SD) | |
Patients characteristics at inclusion | |||||||||||||
Age, years | 40 | 56 | 53 | 47 | 24 | 44 ± 12.7 | 24 | 27 | 52 | 19 | 32 | 30.8 ± 12.7 | 37.4 ± 13.9 |
Sex | M | M | M | F | F | – | M | M | F | F | F | – | – |
Disease duration, monthsb
| 6 | 18 | 29 | 20 | 18 | 18.2 ± 8.2 | 3 | 6 | 27 | 24 | 36 | 19.2 ± 14.1 | 18.7 ± 10.9 |
Steroids at inclusion, mg/day | 7 | 10 | 0 | 10 | 0 | 5.4 ± 5.1 | 0 | 7 | 0 | 0 | 0 | 1.7 ± 3.5 | 3.8 ± 4.6 |
SHAQ (0–3) | – | 0.87 | 2.87 | 1.625 | 2 | 1.8 ± 0.8 | 1.25 | 2 | – | 2.125 | 0.16 | 1.4 ± 0.9 | 1.6 ± 0.8 |
mRSS (0–51) | 26 | 22 | 37 | 29 | 25 | 27.8 ± 5.7 | 16 | 22 | 52 | 42 | 23 | 31 ± 15.2 | 29.4 ± 11.0 |
FVC, % | 56 | 89 | 87 | 108 | 58 | 79.6 ± 22.2 | 52 | 72 | 63 | 56 | – | 60.7 ± 8.8 | 71.2 ± 19.3 |
DLCO, % predicted | 45 | 75 | 72 | 56 | 48 | 59.2 ± 13.7 | 56 | 47 | 72 | 46 | 30 | 50.2 ± 15.4 | 54.7 ± 14.5 |
LVEF, % | 58 | 82 | 62 | 61 | 73 | 67.2 ± 10.0 | 60 | 63 | – | 67 | 70 | 65 ± 4.4 | 66.2 ± 7.7 |
Serum creatinine, μmol/L | 67 | 76 | 77 | – | 51 | 67.8 ± 12.0 | 52 | 73 | 60 | 59 | 71 | 63 ± 8.8 | 65.1 ± 10.0 |
CRP level, mg/L | 62 | 2 | 15 | 20 | 2 | 20.2 ± 24.7 | 9 | 51 | 66 | 13 | 10 | 35 ± 27.8 | 26.8 ± 25.6 |
Anti-Scl-70 antibodies, U/ml | 120 | + | 0 | 10.2 | + | 43.3 ± 66.5 | 0 | + | 39.1 | 130 | 21.3 | 47.6 ± 57.2 | 45.8 ± 55.8 |
Graft characteristics and engraftment duration | |||||||||||||
CD34+ cells × 106 infused/kgc
| 4.9 | 2.9 | 4.9 | 2.5 | 5.3 | 4.1 ± 1.3 | 5.8 | 6.3 | 5.19 | 8.79 | 7.2 | 6.9 ± 2.0 | 5.5 ± 2.2 |
CFU-GM cells × 104 infused/kgd
| 12.37 | 2.7 | – | – | 88 | 34.3 ± 46.7 | 23 | 48 | 9.97 | 52.56 | 91 | 44.9 ± 31.2 | 40.9 ± 34.7 |
Days to 0.5 × 109 neutrophils/L | 10 | 10 | 11 | 10 | 10 | 10.2 ± 0.4 | 10 | 7 | 10 | 9 | 9 | 9 ± 1.2 | 9.6 ± 1.1 |
Days to 20 × 109 platelets/L | 8 | 10 | 10 | 9 | 7 | 8.8 ± 1.3 | 8 | 7 | 10 | 12 | 6 | 8.6 ± 2.4 | 8.7 ± 1.8 |
Days to 50 × 109 platelets/L | 10 | 10 | 13 | 9 | 10 | 10.4 ± 1.5 | 9 | 7 | Not reached | 14 | 9 | 9.7 ± 3.0 | 10.1 ± 2.1 |
Phenotypic analysis of lymphocyte populations after HSCT
Lymphocyte population | Normal range (cell counts/ml) | At inclusion | 2–3 years | 4–5 years | Long term | ||||
---|---|---|---|---|---|---|---|---|---|
Group A | Group B | Group A | Group B | Group A | Group B | Group A | Group B | ||
Total | 1718–2620 | 1862 ± 764 | 1318 ± 748 | 1348 ± 777 | 1034 ± 584 | 1408 ± 937 | 1135 ± 482 | 1579 ± 616 | 1316 ± 624 |
T cells (CD3+) | 1008–1647 | 1135 ± 485 | 957 ± 629 | 937 ± 569 | 713 ± 477 | 917 ± 561 | 749 ± 440 | 1417 ± 187 | 1143 ± 527 |
CD4 T cells (CD3+CD4+) | 587–1009 | 730 ± 163 | 563 ± 373 | 409 ± 269 | 405 ± 305 | 510 ± 315 | 412 ± 269 | 678 ± 345 | 576 ± 367 |
Naive CD4 T cells (CD4 + CD45RA+) | 161–529 | 195 ± 161 | 145 ± 44 | 197 ± 171 | 152 ± 221 | 187 ± 193 | 158 ± 218 | 372 ± 175 | 290 ± 271 |
CD8 T cells (CD3+CD8+) | 313–644 | 459 ± 182 | 345 ± 228 | 453 ± 259 | 282 ± 171 | 410 ± 245 | 299 ± 153 | 571 ± 39 | 443 ± 185 |
B cells (CD19+) | 121–267 | 70 ± 53* | 119 ± 91* | 300 ± 391 | 137 ± 137 | 175 ± 56 | 208 ± 214 | 188 ± 63 | 197 ± 217 |
NK cells (CD3-CD16+CD56+) | 82–340 | 176 ± 108 | 112 ± 34 | 151 ± 64* | 92 ± 113* | 115 ± 55 | 132 ± 100 | 150 ± 92 | 135 ± 101 |
Group A patients | Group B patients | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
1 | 2 | 3 | 4 | 5 | 1 | 2 | 3 | 4 | 5 | |
Anti-Scl-70 antibodies, U/ml | ||||||||||
Baseline | 120 | +a
| 0 | 10.2 | +a
| 0 | +a
| 39.1 | 130 | 21.3 |
2–3 years | 32.9 | 0 | 0 | 0 | 390 | 0 | 240 | 31.1 | 106.5 | 0 |
4–5 years | 11.6 | 0 | 0 | 0 | 257 | 0 | 352 | 15.9 | +a
| 0 |
Long term | 0 | 0b
| 0b
| 0 | >8b
| 0 | 3.8b
| >8b
| 250 | 0 |