Table 1: Characteristics of HCT recipients at first transplantation
|
No BSI
N = 913
(66.9%)
|
BSI
N = 451 (33.06%)
|
Overall
N = 1 364
(100%)
|
p- value
|
Male gender
|
543 (59.5)
|
291 (64.5)
|
834 (61.1)
|
0.072
|
Age at 1st HCT, years (IQR)
|
53 (42 – 61)
|
53 (41 – 61)
|
53 (42 – 61)
|
0.96
|
Karnofsky Score
|
|
|
|
|
≥ 90
|
763 (83.6)
|
358 (79.4)
|
1 121 (82.2)
|
0.11
|
Underlying condition
|
|
|
|
0.39
|
Acute leukaemia
|
479 (52.5)
|
246 (54.5)
|
725 (53.2)
|
|
Chronic leukaemia
|
54 (5.9)
|
28 (6.2)
|
82 (6.0)
|
|
Lymphoma
|
101 (11.1)
|
45 (10.0)
|
146 (10.7)
|
|
MDS/ MPN
|
204 (22.3)
|
86 (19.1)
|
290 (21.3)
|
|
Plasma cell disorders
|
54 (5.9)
|
28 (6.2)
|
82 (6.0)
|
|
Other°
|
21 (2.3)
|
18 (4.0)
|
39 (2.9)
|
|
Number of allogeneic HCT
|
|
|
|
<0.001
|
1
|
894 (97.9)
|
404 (89.6)
|
1 298 (95.2)
|
|
2
|
17 (1.9)
|
47 (10.4)
|
64 (4.7)
|
|
3
|
2 (0.2)
|
0
|
2 (0.1)
|
|
Interval from 1st to 2nd transplant, days (IQR)
|
578 (461 – 785)
|
418 (246 – 663)
|
517 (258 – 665)
|
0.096
|
Graft source
|
|
|
|
0.17
|
Peripheral blood
|
806 (88.3)
|
385 (85.4)
|
1 191 (87.3)
|
|
Bone marrow
|
104 (11.4)
|
62 (13.7)
|
166 (12.2)
|
|
Cord blood
|
3 (0.3)
|
4 (0.9)
|
7 (0.5)
|
|
Donor:
|
|
|
|
0.038
|
Related
|
429 (47.0)
|
189 (41.9)
|
618 (45.3)
|
|
Unrelated
|
478 (52.4)
|
262 (58.1)
|
740 (54.3)
|
|
Syngeneic
|
6 (0.7)
|
0
|
6 (0.4)
|
|
Regimen
|
|
|
|
0.010
|
Myeloablative conditioning
|
454 (49.7)
|
258 (57.2)
|
712 (52.2)
|
|
Reduced conditioning
|
458 (50.2)
|
193 (42.8)
|
651 (47.7)
|
|
Engraftment (day 0 – 100)
|
|
|
|
0.15
|
Yes
|
858 (94.0)
|
413 (91.6)
|
1 271 (93.2)
|
|
No
|
11 (1.2)
|
12 (2.7)
|
23 (1.7)
|
|
Never below/ missing
|
44 (4.8)
|
26 (5.8)
|
70 (5.1)
|
|
Time to engraftment, median days (IQR)
|
15 (12 – 18)
|
16 (14 – 19)
|
15 (13 – 18)
|
<0.001
|
Acute Graft vs. Host Disease
|
|
|
|
<0.001
|
Grade I/ II
|
321 (35.2)
|
135 (29.9)
|
456 (33.4)
|
|
Grade III/ IV
|
73 (8.0)
|
82 (18.2)
|
155 (11.4)
|
|
Present, grade unknown
|
9 (1.0)
|
5 (1.1)
|
14 (1.0)
|
|
Not evaluated/ missing
|
33 (3.6)
|
35 (7.8)
|
68 (5.0)
|
|
Follow-up time, person-years (IQR)
|
2.03
(0.9 – 4.1)
|
1.4
(0.5 – 3.2)
|
1.8
(0.7 – 4.0)
|
0.001
|
Data are n (%) or median (IQR) if indicated, HCT haematopoetic cell transplantation, MDS/ MPN myelodysplastic syndrome/myeloproliferative neoplasm
°Other: bone marrow failure n=28 (2.1%), inherited disorders n=7 (0.5%), hemoglobinopathies n=1 (0.1%), Infection n=1 (0.1%), other n=2 (0.1%).
Table 2. Distribution of pathogens and antimicrobial resistance over the two time periods
|
10/09/2009 –04/02/2015
N = 322 (41.2%)
|
05/02/2015 – 09/10/2018
N = 459 (58.7%)
|
Total
N = 781
(100 %)
|
p-value
|
Coagulase-negative staphylococci
|
N = 107 (33.2)
|
N = 103 (22.4)
|
N = 210 (26.9)
|
|
Resistant to oxacillin
|
105 (98.1)
|
100 (97.1)
|
205 (97.6)
|
0.62
|
Staphylococcus aureus
|
N = 4 (1.2)
|
N = 5 (1.1)
|
N = 9 (1.2)
|
|
Resistant to oxacillin
|
0
|
0
|
0
|
|
Streptococcus spp.
|
N = 37 (11.5)
|
N = 40 (8.7)
|
N = 77 (9.9)
|
|
Resistant to penicillin
|
6 (16.2)
|
10 (25.0)
|
16 (20.7)
|
0.41
|
Enterococcus faecium
|
N = 54 (16.8)
|
N = 62 (13.5)
|
N = 116 (14.9)
|
|
Resistant to vancomycin
|
0
|
1 (1.6)
|
1 (0.9)
|
0.35
|
Resistant to daptomycin
|
1 (1.9)
|
2 (3.3)
|
3 (2.6)
|
0.97
|
Enterococcus faecalis
|
N = 9 (2.8)
|
N = 8 (1.7)
|
N = 17 (2.2)
|
|
Resistant to ampicillin
|
2 (22.0)
|
0
|
2 (11.0)
|
0.13
|
Enterobacterales
|
N = 59 (18.3)
|
N = 136 (29.6)
|
N = 195 (25.0)
|
|
Resistant to ciprofloxacin
|
25 (42.4)
|
56 (41.2)
|
81 (41.5)
|
0.85
|
Resistant to cefepime
|
11 (18.6)
|
22 (16.2)
|
33 (16.9)
|
0.68
|
Resistant to piperacillin/ tazobactam
|
10 (16.9)
|
22 (16.2)
|
32 (16.4)
|
0.93
|
Resistant to meropenem
|
2 (3.4)
|
0
|
2 (1.0)
|
|
ESBL-producing
|
13 (22.0)
|
28 (20.6)
|
41 (21.0)
|
0.72
|
Chromosomal AmpC
|
5 (8.5)
|
8 (5.9)
|
13 (6.7)
|
0.52
|
Carbapenemases
|
0
|
0
|
0
|
|
Pseudomonas aeruginosa
|
N = 18 (5.6)
|
N = 31 (6.8)
|
N = 49 (6.3)
|
|
Resistant to ciprofloxacin
|
4 (22.2)
|
7 (22.6)
|
11 (22.4)
|
0.91
|
Resistant to piperacillin/ tazobactam
|
2 (11.1)
|
10 (32.2)
|
12 (24.5)
|
0.12
|
Resistant to cefepime
|
2 (11.1)
|
4 (12.9)
|
6 (12.2)
|
0.91
|
Resistant to meropenem
|
4 (22.2)
|
6 (19.3)
|
10 (20.4)
|
0.82
|
Resistant to piperacillin/ tazobactam, cefepime and carbapenems
|
2 (11.1)
|
2 (6.5)
|
4 (8.2)
|
0.85
|
Anaerobes
|
N = 5 (1.6)
|
N = 21 (4.6)
|
N = 26 (3.3)
|
|
Resistant to penicillin
|
0
|
12 (57.0)
|
12 (46.0)
|
0.05
|
Candida albicans
|
N = 2 (0.6)
|
N = 1 (0.2)
|
N = 3 (0.4)
|
|
Resistant to fluconazol
|
0
|
0
|
0
|
|
Candida non-albicans
|
N = 11 (3.4)
|
N = 9 (2.0)
|
N = 20 (2.6)
|
|
Resistant to fluconazol
|
8 (72.7)
|
7 (77.7)
|
15 (75.0)
|
0.44
|
Resistant to caspofungin
|
1 (9.0)
|
1 (11.1)
|
2 (10.0)
|
0.70
|
Other pathogens
|
N = 16 (5.0)
|
N = 43 (9.4)
|
N = 59 (7.6)
|
|
Observations divided into two time periods with 4th of February 2015 representing the median of HCTs. Pathogens tested intermediary and resistant according to old EUCAST definitions were collected as resistant. ESBL extended spectrum beta-lactamase. CPE carbapenemase-producing Enterobacterales.
Table 3: Risk factors for bloodstream infections
|
Univariate analysis
|
Multivariate analysis
|
|
HR (95% CI)
|
p- value
|
HR (95% CI)
|
p- value
|
Gender, male vs. female
|
1.28 (1.03 – 1.59)
|
0.025
|
1.26 (1.01 – 1.57)
|
0.039
|
|
Age, ≥60 vs. <60 years
|
1.08 (0.86 – 1.35)
|
0.524
|
1.04 (0.81 – 1.34)
|
0.749
|
|
Karnofsky score at transplantation°, ≥90% vs. <90%
|
0.73 (0.57 – 0.95)
|
0.017
|
0.79 (0.61 – 1.03)
|
0.083
|
|
Comorbidities, present vs. absent
|
1.52 (1.24 – 1.87)
|
<0.001
|
1.48 (1.19 – 1.83)
|
<0.001
|
|
AML, present vs. other haematological conditions
|
1.05 (0.86 – 1.29)
|
0.636
|
1.05 (0.85 – 1.30)
|
0.658
|
|
Conditioning regimen
MAC vs. RIC
|
|
|
|
|
|
-14d – 30d
|
1.69 (1.30 – 2.21)
|
<0.001
|
1.82 (1.38 – 2.42)
|
<0.001
|
|
31d – 365d
|
0.74 (0.52 – 1.06)
|
0.103
|
0.91 (0.62 – 1.33)
|
0.626
|
|
Graft cell source, cord blood vs. other graft sources
|
2.61 (0.98 – 7.01)
|
0.056
|
2.18 (0.80 – 5.95)
|
0.128
|
|
HLA- match, unrelated vs. related donor
|
1.2 (0.97 – 1.48)
|
0.088
|
1.13 (0.91 – 1.40)
|
0.276
|
|
Neutrophil recovery°
post-engraftment vs. aplasia
|
0.39 (0.24 – 0.64)
|
<0.001
|
0.44 (0.26 – 0.73)
|
0.002
|
|
aGvHD°, present vs. absent
|
|
|
|
|
|
Grade I/II
|
1.44 (0.94 – 2.20)
|
0.091
|
1.48 (0.96 – 2.27)
|
0.078
|
|
Grade III/IV
|
6.55 (4.50 – 9.53)
|
<0.001
|
6.62 (4.52 – 9.69)
|
<0.001
|
|
Progression/relapse of haematological disease°, present vs. absent
|
2.84 (1.87 – 4.29)
|
<0.001
|
3.11 (2.04 – 4.73)
|
<0.001
|
|
|
|
|
|
|
|
|
|
AML acute myeloid leukemia; aGVHD acute graft-versus-host-disease; HCT haematopoietic cell transplantation; MAC myeloablative conditioning; RIC reduced-intensity conditioning, °Time- dependent covariates. Non-time- dependent covariates are assessed at the time point of first HCT
Table 4: Risk factors for mortality
|
Univariate analysis
|
Multivariate analysis
|
|
HR (95% CI)
|
p- value
|
HR (95% CI)
|
p- value
|
Gender, male vs. female
|
1.02 (0.82 – 1.27)
|
0.857
|
0.97 (0.78 – 1.21)
|
0.775
|
|
Age, ≥60 vs. <60 years
|
1.31 (1.05 – 1.64)
|
0.017
|
1.07 (0.84 – 1.37)
|
0.561
|
|
Karnofsky score at transplantation°, ≥90% vs. <90%
|
0.47 (0.37 – 0.59)
|
<0.001
|
0.55 (0.43 – 0.71)
|
<0.001
|
|
Comorbidities, present vs. absent
|
1.63 (1.32 – 2.01)
|
<0.001
|
1.34 (1.07 – 1.67)
|
0.011
|
|
AML, present vs. other haematological conditions
|
1.03 (0.83 – 1.27)
|
0.789
|
0.86 (0.69 – 1.07)
|
0.167
|
|
Number of HCT°, >1 vs. 1
|
3.8 (1.95 – 7.39)
|
<0.001
|
1.37 (0.67 – 2.79)
|
0.389
|
|
Conditioning regimen, MAC vs. RIC
|
0.72 (0.59 – 0.89)
|
0.003
|
0.89 (0.70 – 1.12)
|
0.311
|
|
Graft cell source, cord blood vs. other graft sources
|
1.19 (0.30 – 4.78)
|
0.805
|
0.81 (0.20 – 3.27)
|
0. 762
|
|
aGvHD°, present vs. absent
|
|
|
|
|
|
Grade I/II
|
0.9 (0.68 – 1.20)
|
0.485
|
0.91 (0.68 – 1.21)
|
0.517
|
|
Grade III/IV
|
2.84 (2.14 – 3.78)
|
<0.001
|
2.39 (1.77 – 3.24)
|
<0.001
|
|
Progression/Relapse of haematological disease°, present vs. absent
|
10.0 (7.94 – 12.6)
|
<0.001
|
9.4 (7.41 – 11.91)
|
<0.001
|
|
HLA- match, unrelated vs. related donor
|
|
|
|
|
|
-14 – 30 days
|
3.17 (1.05 – 9.57)
|
0.040
|
2.9 (0.96 – 8.75)
|
0.059
|
|
31 – 100 days
|
1.49 (0.97 – 2.31)
|
0.072
|
1.61 (1.03 – 2.51)
|
0.037
|
|
101 – 365 days
|
1.18 (0.92 – 1.53)
|
0.197
|
1.16 (0.89 – 1.50)
|
0.270
|
|
Bloodstream infection °, present vs. absent
|
|
|
|
|
|
-14 – 30 days
|
6.06 (2.42 – 15.17)
|
<0.001
|
5.95 (2.38 – 14.86)
|
<0.001
|
|
31 – 100 days
|
7.34 (3.80 – 14.18)
|
<0.001
|
4.41 (2.33 – 8.34)
|
<0.001
|
|
101 – 365 days
|
20.57 (15.2 – 27.8)
|
<0.001
|
10.7 (7.8 – 14.7)
|
<0.001
|
|
AML acute myeloid leukemia; aGVHD acute graft-versus-host-disease; HCT haematopoietic cell transplantation; MAC myeloablative conditioning; RIC reduced-intensity conditioning
°Time-dependent covariates. Non-time- dependent covariates are assessed at the timepoint of first HCT