01.12.2017 | Rapid communication | Ausgabe 1/2017 Open Access

Long-term immune reconstitution and T cell repertoire analysis after autologous hematopoietic stem cell transplantation in systemic sclerosis patients
- Zeitschrift:
- Journal of Hematology & Oncology > Ausgabe 1/2017
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, months
b
|
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
|
DL
CO, % 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 × 10
6 infused/kg
c
|
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 × 10
4 infused/kg
d
|
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 × 10
9 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 × 10
9 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 × 10
9 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
|
0
b
|
0
b
|
0
|
>8
b
|
0
|
3.8
b
|
>8
b
|
250
|
0
|