Background
Methods
Study design and data collection
Statistical analysis
Results
Patient, disease, and transplant characteristics
Patient characteristics | HLA 10/10 | HLA 9/10 | HLA 8/10 |
p value |
---|---|---|---|---|
Number of patients | 2567 | 723 | 108 | |
Recipient age at SCT (years, range) | 61 (50–78) | 61 (50–77) | 60 (50–73) | 0.584 |
Recipient gender, n (%) | 0.707 | |||
Male | 1386 (54 %) | 387 (53.7 %) | 62 (58 %) | |
Female | 1177 (46 %) | 334 (46.3 %) | 45 (42 %) | |
Year of SCT (median), year (%) | 2011 (00–13) | 2011 (02–13) | 2009 (00–13) | 0.001 |
Interval from diagnosis to SCT (days) | 212 | 250 | 295 | 0.0001 |
Median follow-upa (months, range) | 24 (1–150) | 24 (1–139) | 34 (3–117) | 0.042 |
Donor age (years, range) | 33 (16–61) | 36 (20–61) | 35 (20–55) | 0.02 |
Donor gender, n (%) | <10−4
| |||
Male | 1845 (73 %) | 463 (65.2 %) | 69 (64.5 %) | |
Female | 682 (27 %) | 247 (34.8 %) | 38 (35.5 %) | |
Female donor to male recipient, n (%) | 281 (11.1 %) | 106 (15 % ) | 17 (16 % ) | 0.01 |
Diagnosis, n (%) | 0.001 | |||
De novo AML | 1805 (70.3 %) | 527 (72.9 %) | 60 (55.6 %) | |
Secondary AML | 762 (29.7 %) | 196 (27.1 %) | 48 (44.4 %) | |
Cytogenetics in de novo AML, n (% of available data) | 0.235 | |||
Good | 75 (9.2 %) | 15 (5.9 %) | 2 (7.1 %) | |
Intermediate | 545 (67.2 %) | 183 (72 %) | 23 (82 %) | |
Poor | 191 (23.5 %) | 56 (22 %) | 3 (10.7 %) | |
Not available/failed | 994 (55 %) | 273 (51.8 %) | 32 (53.3 %) | |
Disease status at SCT, n (%) | 0.0002 | |||
CR1 | 1413 (55 %) | 333 (46.1 %) | 48 (44.4 %) | |
≥CR2 | 504 (19.7 %) | 171 (23.6 %) | 25 (23.2 %) | |
Active disease | 650 (25.3 %) | 219 (30.3 %) | 35 (32.4 %) | |
Source of SC, n (%) | 0.173 | |||
BM | 154 (6 %) | 56 (7.8 %) | 9 (8.3 %) | |
PB | 2413 (94 %) | 667 (92.2 %) | 99 (91.7 %) | |
Conditioning, n (%) | 0.02 | |||
Chemo alone | 1836 (71.5 %) | 550 (76.1 %) | 84 (77.8 %) | |
Low TBI | 731 (28.5 %) | 173 (23.9 %) | 24 (22.2 %) | |
In vivo T cell depletion, n (%) | <10−4
| |||
No | 672 (26.4 %) | 121 (16.9 %) | 15 (14.0 %) | |
ATG | 1460 (57.5 %) | 468 (65.2 %) | 59 (55.1 %) | |
Campath | 409 (16.1 %) | 129 (18.0 %) | 33 (30.8 %) | |
Post-transplant GVHD prophylaxis | 0.07 | |||
CsA | 504 (19.9 %) | 135 (18.8 %) | 27 (25.5 %) | |
CsA/FK 506 + MTX | 517 (20.4 %) | 177 (24.7 %) | 16 (15.1 %) | |
CsA/FK 506 + MMF | 1353 (53.4 %) | 353 (49.2 %) | 53 (50 %) | |
Other | 160 (6.3 %) | 53 (7.4 %) | 10 (9.4 %) | |
Missing | 33 | 5 | 2 | |
Karnosky at SCT, n (%) | 0.47 | |||
≤80 % | 173 (6.7 %) | 42 (5.8 %) | 9 (8.4 %) | |
>80 % | 2231 (86.9 %) | 641 (88.7 %) | 91 (84.2 %) | |
Missing | 163 (6.4 %) | 40 (5.5 %) | 8 (7.4 %) | |
Patient positive CMV serology, n (%) | 1634 (64.9 %) | 492 (69.1 %) | 67 (63.8 %) | 0.10 |
CMV risk, n (%) | 0.029 | |||
Low | 695 (27.8 %) | 155 (21.9 %) | 26 (24.8 %) | |
Intermediate | 1072 (42.8 %) | 316 (44.7 %) | 47 (44.8 %) | |
High | 734 (29.4 % ) | 236 (33.4 %) | 32 (30.5 %) |
Engraftment and GVHD
HLA 10/10 | HLA 9/10 | HLA 8/10 |
p value | |
---|---|---|---|---|
Total number of patients | 2567 | 723 | 108 | |
Engraftment, n (%) | 2458 (97.3 %) | 678 (96.3 %) | 101 (97.12 %) | 0.313 |
No engraftment, n (%) | 67 (2.7 %) | 26 (3.7 %) | 3 (2.9 %) | |
Missing, n
| 42 | 19 | 5 | |
Median time ANC >0.5 G/L (days, range) | 16 (0–103) | 16 (1–165) | 15.5 (1–33) | 0.538 |
Acute GVHD, | ||||
Grade 0–I, n (%) | 1826 (74.4 %) | 469 (67.2 %) | 67 (65.7 %) | 0.0002 |
Grades II–IV, n (%) | 629 (25.6 %) | 229 (32.8 %) | 35 (34.3 %) | |
Grades III–IV, n (%) | 234 (9.5 %) | 90 (12.9 %) | 11 (10.8 %) | 0.035 |
Missing, n
| 75 | 21 | 3 | |
Chronic GVHDa
| ||||
All grades | 35.0 % [32.9–37.2] | 35.1 % [31.2–39] | 44.4 % [33.6–54.6] | 0.138 |
Extensive | 17.1 % [15.4–18.9] | 15.2 % [12.3–18.5] | 26.1 % [16.8–36.4] | 0.047 |
Limited, n
| 369 | 109 | 14 | |
Extensive, n
| 324 | 80 | 21 | |
Missing, n
| 38 | 18 | 5 |
Disease status | Patients group and p value | RI | NRM | LFS | OS | cGVHD | Extensive cGVHD |
---|---|---|---|---|---|---|---|
All | 10/10 | 30.1 % [28.2–32.1] | 24.2 % [16.4–32.9] | 45.6 % [43.5–47.7] | 50.6 % [48.5–52.8] | 35.0 % [32.9–37.2] | 17.1 % [15.4–18.9] |
9/10 | 32.5 % [28.9–36.3] | 31.6 % [23–40.5] | 35.8 % [32–39.7] | 41.3 % [37.3–45.3] | 35.1 % [31.2–39] | 15.2 % [12.3–18.5] | |
8/10 | 24.2 % [16.4–32.9] | 35.5 % [26.6–44.4] | 40.3 % [30.6–50] | 43.5 % [33.6–53.3] | 44.4 % [33.6–54.6] | 26.1 % [16.8–36.4] | |
p value | 0.152 | 0.002 | 0.0001 | 0.0001 | 0.138 | 0.047 | |
CR1 | 10/10 | 24.8 % [22.4–27.3] | 22.5 % [11.6–35.7] | 52.6 % [49.7–55.5] | 56.7 % [53.8–59.6] | 37.6 % [34.7–40.5] | 18.1 % [15.8–20.5] |
9/10 | 31.6 % [26.3–37.2] | 26.8 % [14.8–40.2] | 41.6 % [35.7–47.5] | 46.1 % [40.1–52.2] | 35.9 % [30–41.9] | 13 % [9.1–17.7] | |
8/10 | 17.7 % [8.1–30.2] | 33.3 % [20.4–46.8] | 49% [34.3–63.7] | 50.2 % % [35.2–65.1] | 43.4 % [26.4–59.2] | 22.1 % [9.5–37.9] | |
p value | 0.010 | 0.136 | 0.005 | 0.005 | 0.641 | 0.107 | |
≥CR2 | 10/10 | 32.6 % [28.2–37.1] | 24.1 % [8.7–43.5] | 43.3 % [38.5–48.1] | 50.1 % [45.3–55] | 35 % [30.3–39.7] | 13.9 % [10.6–17.7] |
9/10 | 26.3 % [19.5–33.5] | 32.5 % [14.6–51.8] | 41.2 % [33.3–49.2] | 48 % [40–56.1] | 34.7 % [26.8–42.7] | 18.3 % [12.1–25.6] | |
8/10 | 22.4 % [7.7–41.7] | 24.6 % [9.1–44.1] | 53 % [31.3–74.7] | 62 % [40.8–83.3] | 65.5 % [39.6–82.4] | 32.2 % [13.8–52.3] | |
p value | 0.304 | 0.089 | 0.290 | 0.253 | 0.010 | 0.020 | |
Act. dis. | 10/10 | 39.7 % [35.7–43.7] | 28 % [13.8–44] | 32.3 % [28.4–36.3] | 37.9 % [33.8–42] | 29.4 % [25.5–33.4] | 17.5 % [14–21.5] |
9/10 | 38.4 % [31.6–45.3] | 38 % [22.3–53.6] | 23.6 % [17.4–29.7] | 29.1 % [22.5–35.7] | 33.9 % [27.1–40.8] | 16.1 % [10.7–22.5] | |
8/10 | 34.3 % [19–50.2] | 45.7 % [29.7–60.4] | 20 % [6.7–33.3] | 22.9 % [8.9–36.8] | 30 % [14.4–47.4] | 26.1 % [10.1–45.5] | |
p value | 0.902 | 0.062 | 0.107 | 0.139 | 0.587 | 0.578 | |
In vivo | No | 28.8 % [25.4–32.3] | 27.1 % [23.7–30.7] | 44 % [40.1–48] | 47.7 % [43.7–51.8] | 45 % [40.8–49] | 26.4 % [22.5–30.4] |
T cell | Yes | 30.7 % [28.8–32.6] | 25.9 % [22.5–29.4] | 43.4 % [41.3–45.5] | 48.8 % [46.7–50.9] | 32.9 % [30.9–34.9] | 14.6 % [13–16.2] |
Depletion |
p value | 0.920 | 0.448 | 0.613 | 0.448 | 1.0483e-05 | 1.337e-09 |
HLA 10/10 | HLA 9/10 | HLA 8/10 | |
---|---|---|---|
Relapse | 552 (47.5 %) | 173 (43.4 %) | 21 (36.2 %) |
Infection | 249 (21.3 %) | 100 (25.1 %) | 21 (36.2 %) |
GVHD | 202 (17.3 %) | 80 (20.1 %) | 10 (17.2 %) |
Graft failure/rejection | 11 (0.9 %) | 1 (0.3 %) | 0 |
Cardiac toxicity | 8 (0.7 %) | 4 (1 %) | 1 (1.7 %) |
Haemorhage | 14 (1.2 %) | 5 (1.3 %) | 1 (1.7 %) |
VOD | 12 (1 %) | 8 (2 %) | 0 |
Idiopathic pneumonia | 25 (2.1 %) | 9 (2.3 %) | 0 |
Second malignancy | 24 (2.1 %) | 5 (1.3 %) | 0 |
Other SCT-related | 70 (6 %) | 14 (3.5 %) | 4 (6.9 %) |
Relapse | NRM | Acute GVHD | Chronic GVHD | LFS | OS | |||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
p value | HR (95 % CI) |
p value | HR (95 % CI) |
p value | OR (95 % CI) |
p value | HR (95 % CI) |
p value | HR (95 % CI) |
p value | HR (95 % CI) | |
HLA 10/10 (ref) | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 | ||||||
HLA 9/10 versus 10/10 | 0.038 | 1.18 (1.01–1.38) | 0.001 | 1.34 (1.13–1.58) | 0.0001 | 1.47 (1.21–1.79) | 0.418 | 1.07 (0.91–1.26) | 0.0001 | 1.25 (1.11–1.40) | 0.0001 | 1.27 (1.13–1.44) |
HLA 8/10 versus 9/10 | 0.064 | 0.67 (0.43–1.02) | 0.398 | 1.17 (0.81–1.68) | 0.952 | 1.01 (0.63–1.62) | 0.145 | 1.31 (0.91–1.88) | 0.432 | 0.90 (0.68–1.18) | 0.557 | 0.92 (0.69–1.22) |
Age at SCT (10 years) | 0.701 | 1.02 (0.91–1.15) | <10−5
| 1.41 (1.24–1.59) | 0.465 | 1.05 (0.91–1.22) | 0.501 | 1.04 (0.93–1.17) | 0.0001 | 1.18 (1.09–1.29) | <10−5
| 1.25 (1.14–1.37) |
Interval diag. to SCTa
| 0.007 | 0.96 (0.93–0.99) | 0.636 | 1.01 (0.98–1.03) | 0.306 | 0.98 (0.95–1.02) | 0.833 | 1.00 (0.97–1.02) | 0.108 | 0.98 (0.96–1.00) | 0.122 | 0.98 (0.96–1.00) |
Disease status at SCT | ||||||||||||
CR1 (ref) | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 | ||||||
CR2 versus CR1 | 4.10−5
| 1.50 (1.24–1.82) | 0.713 | 1.04 (0.85–1.28) | 0.728 | 1.04 (0.82–1.32) | 0.558 | 1.06 (0.88–1.28) | 0.002 | 1.25 (1.09–1.44) | 0.016 | 1.20 (1.03–1.39) |
Act.dis. versus CR1 | <10−5
| 2.06 (1.76–2.42) | 0.001 | 1.35 (1.14–1.60) | 0.004 | 1.34 (1.1–1.63) | 0.019 | 1.22 (1.03–1.45) | <10−5
| 1.69 (1.51–1.90) | <10−5
| 1.63 (1.44–1.84) |
Secondary AML | 0.699 | 0.97 (0.83–1.13) | 0.0004 | 1.32 (1.13–1.54) | 0.418 | 1.08 (0.90–1.30) | 0.196 | 1.11 (0.95–1.29) | 0.029 | 1.13 (1.01–1.26) | 0.021 | 1.14 (1.02–1.28) |
Karnofsky ≥80 % | 0.149 | 0.83 (0.64–1.07) | <10−5
| 0.55 (0.43–0.70) | 0.838 | 0.97 (0.70–1.33) | 0.318 | 0.86 (0.64–1.16) | 10−5
| 0.68 (0.57–0.81) | <10−5
| 0.63 (0.58–0.76) |
TBI | 0.005 | 1.26 (1.07–1.48) | 0.767 | 1.03 (0.85–1.24) | 0.088 | 0.83 (0.67–1.03) | 0.610 | 1.04 (0.88–1.24) | 0.019 | 1.16 (1.02–1.30) | 0.022 | 1.16 (1.02–1.32) |
In vivo T cell depletion | 0.483 | 1.07 (0.89–1.27) | 0.253 | 0.90 (0.74–1.08) | <10−5
| 0.61 (0.49–0.75) | 0.0001 | 0.72 (0.61–0.85) | 0.790 | 0.98 (0.86–1.12) | 0.72 | 0.98 (0.85–1.12) |
Female D to male R | 0.112 | 0.84 (0.68–1.04) | 0.172 | 1.15 (0.94–1.42) | 0.063 | 1.26 (0.99–1.61) | 0.078 | 1.19 (0.98–1.45) | 0.846 | 0.99 (0.85–1.14) | 0.896 | 1.01 (0.87–1.18) |
High CMV risk (R+/D−) | 0.665 | 1.04 (0.87–1.24) | 0.002 | 1.35 (1.11–1.65) | 0.028 | 1.28 (1.03–1.60) | 0.814 | 0.98 (0.82–1.17) | 0.019 | 1.17 (1.03–1.33) | 0.001 | 1.25 (1.09–1.43) |