Background
Methods
Study design and randomization
Patients and eligibility criteria
Conditioning and transplants
GVHD prophylaxis
CMV-DNA and EBV-DNA monitoring
Pre-emptive therapy for EBV and CMV DNAemia
Immune reconstitution
Evaluation points and definition
Statistical analysis
Results
Study population
7.5 mg group (N = 203) | 10.0 mg group (N = 205) |
P
| |
---|---|---|---|
Patient age, median (range), years | 28 (14–59) | 26 (14–57) | 0.324 |
Gender, male/female, n (%) | 139 (68.5)/64 (31.5) | 139 (67.5)/66 (32.2) | 0.885 |
Primary diseases, n (%) | 0.483 | ||
AML (cytogenetics) | 99 (48.8) | 95 (46.3) | |
Better risk | 8 (8.1) | 7 (7.4) | |
Intermediate risk | 41 (41.4) | 41 (43.1) | |
Poor risk | 36 (36.4) | 32 (33.7) | |
Unknown | 14 (14.1) | 15 (15.8) | |
ALL | 94 (46.3) | 94 (45.6) | |
Ph positive | 29 (30.9) | 31 (33.0) | |
Ph negative | 65 (69.1) | 63 (67.0) | |
ABL/ALAL | 10 (4.9) | 16 (7.8) | |
Number of courses of chemotherapy before transplantation, median (range) | 3 (3–9) | 3 (3–7) | 0.875 |
Status of primary disease, n (%) | 0.318 | ||
CR1 | 155 (76.4) | 143 (69.7) | |
≥ CR2 | 10 (4.9) | 12 (5.9) | |
Non-CR | 38 (18.7) | 50 (24.4) | |
Conditioning, n (%) | 0.164 | ||
Standard myeloablative regimen | 165 (81.3) | 155 (75.6) | |
Intensified conditioning | 38 (18.7) | 50 (24.3) | |
No. of HLA mismatched, n (%) | 0.479 | ||
1 | 14 (6.9) | 15 (7.3) | |
2–3 | 51 (25.1) | 62 (30.2) | |
4–5 | 138 (68.0) | 128 (62.1) | |
Donor age, median (range), years | 38 (10–59) | 40 (15–59) | 0.326 |
Donor–recipient sex match, n (%) | 0.850 | ||
Male–male | 90 (44.3) | 92 (44.9) | |
Male–female | 41 (20.2) | 47 (22.9) | |
Female–male | 55 (27.1) | 52 (25.4) | |
Female–female | 17 (8.4) | 14 (6.8) | |
CMV serostatus, n (%) | 0.906 | ||
D−/R− | 8 (3.9) | 10 (4.9) | |
D+/R− | 7 (3.4) | 7 (3.4) | |
D−/R+ | 5 (2.5) | 7 (3.4) | |
D+/R+ | 183 (90.1) | 181 (88.3) | |
EBV serostatus, n (%) | 0.940 | ||
D−/R− | 9 (4.4) | 10 (4.9) | |
D+/R− | 47 (23.2) | 50 (24.3) | |
D−/R+ | 34 (16.7) | 30 (14.6) | |
D+/R+ | 113 (55.7) | 115 (56.1) | |
Median CD34+ cells per graft, × 106/kg (range) | 2.26 (0.32–7.37) | 2.58 (0.71–7.39) | 0.205 |
Engraftment
EBV and CMV infections
Risk factors | EBV DNAemia | EBV-associated disease | CMV DNAemia | CMV-associated diseases | ||||
---|---|---|---|---|---|---|---|---|
HR(95%CI) |
P
| HR, 95%CI |
P
| HR, 95%CI | P | HR, 95%CI |
P
| |
Patient gender | ||||||||
Male | 1 | 0.084 | 1 | 0.110 | 1 | 0.140 | 1 | 0.560 |
Female | 0.70 (0.47–1.05) | 0.35(0.10–1.26) | 1.18 (0.95–1.48) | 0.71 (0.23–2.23) | ||||
Patient age | ||||||||
< 27 years | 1 | 0.570 | 1 | 0.300 |
1
|
0.003
| 1 | 0.470 |
≥ 27 years | 0.90 (0.63–1.29) | 1.58,(0.67–3.74) |
1.39 (1.11–1.73)
| 0.69 (0.24–1.93) | ||||
Conditioning | ||||||||
BuCy |
1
|
0.005
|
1
| 0.061 | 1 | 0.380 | 1 | 0.420 |
Intensified |
1.73 (1.18–2.54)
|
2.28 (0.96–5.42)
| 0.88 (0.67–1.17) | 1.55 (0.54–4.45) | ||||
EBV serostatus, | – | – | ||||||
Other | 1 | 0.046 |
1
|
0.038
| – | – | ||
D−/R+ | 1.58 (1.01–2.46) |
2.85 (1.06–7.670
| ||||||
CMV serostatus | – | – | ||||||
Other | – | – | 1 | 0.420 | 1 | 0.051 | ||
D−/R+ | 0.79 (0.44–1.41) | 4.54 (0.99–20.78) | ||||||
ATG dose, | ||||||||
7.5 mg/kg |
1
|
< 0.001
|
1
| 0.065 |
1
|
0.013
|
1
|
0.050
|
10.0 mg/kg |
2.02 (1.37–2.97)
|
2.45 (0.95–6.33)
|
1.31 (1.06–1.62)
|
3.65 (1.00–13.32)
|
aGVHD and cGVHD
Immune reconstitution
Months after transplantation | EBV-CTLs (spots/105 cells) | CMV-CTLs (spots/105 cells) | ||||
---|---|---|---|---|---|---|
7.5 mg/kg group, mean counts (range) | 10.0 mg/kg group, mean counts (range) |
P
| 7.5 mg/kg group, mean counts (range) | 10.0 mg/kg group, mean counts (range) |
P
| |
1st | 50.08 (23–136) | 38.61 (16–110) | 0.249 | 57.38 (20–163) | 45.56 (19–131) | 0.312 |
2nd | 89.23 (34–254) | 47.28 (20–173) |
0.046
| 131.08 (75–465) | 69.72 (21–311) | 0.050 |
3rd | 166.08 (45–528) | 97.17 (26–364) | 0.189 | 167.08 (30–501) | 110.67 (29–399) | 0.229 |
6th | 122.38 (38–458) | 108.94 (24–453) | 0.752 | 84.38 (35–258) | 75.44 (24–301) | 0.698 |