1. Peking University People’s Hospital, Peking University Institute of Hematology, Beijing 100044, China 2. Peking-Tsinghua Center for Life Sciences, Beijing 100044, China 3. Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing 100044, China 4. Peking University People’s Hospital, Department of Clinical Laboratory, Beijing 100044, China
We aimed to identify the effect of positive stool cultures (PSCs) on the clinical outcomes of patients undergoing haploidentical hematopoietic stem cell transplantation (haplo-HSCT) (n = 332). PSCs were observed in 61 patients (PSC group, 18.4%). Enterobacteriaceae in stool specimens was associated with a higher risk of bloodstream infection, and Candida in stool specimens was related to a higher risk of platelet engraftment failure. The cumulative incidence of infection-related mortality 1 year after haplo-HSCT in the PSC group was higher than that of the patients who showed persistently negative stool cultures (NSC group; 19.2% vs. 8.9%, P = 0.017). The probabilities of overall survival (71.4% vs. 83.8%, P = 0.031) and disease-free survival (69.6% vs. 81.0%, P = 0.048) 1 year after haplo-HSCT for the PSC group were significantly lower than those for the NSC group, particularly for patients who had Candida in their stool specimens. In multivariate analysis, Candida in stool specimens significantly increased the risk of mortality and was associated with poorer survival. Our results showed that PSC influenced the clinical outcomes after haplo-HSCT, particularly those who had Candida in their stool specimens.
Disease risk index before transplantation, no. (%)
Low risk
52 (19.2)
10 (16.4)
0.363
Intermediate risk
187 (69.0)
40 (65.6)
High risk
28 (10.3)
11 (18.0)
Very high risk
4 (1.5)
0 (0.0)
No. of HLA-A, -B, and -DR mismatch, no. (%)
3/6
229 (84.5)
48 (78.7)
0.462
4/6
33 (12.2)
10 (16.4)
5/6
9 (3.3)
3 (4.9)
Previous HSCT, no. (%)a
3 (1.1)
0 (0.0)
1.000
Donor–recipient sex match, no. (%)
Female–male
39 (14.4)
8 (13.1)
0.796
Others
232 (85.6)
53 (86.9)
Donor–recipient relations, no. (%)
Father
123 (45.4)
31 (50.8)
0.207
Mother
12 (4.4)
5 (8.2)
Sibling
55 (20.3)
14 (23.0)
Child
74 (27.3)
9 (14.8)
Others
7 (2.6)
2 (3.2)
Donor–recipient blood type, no. (%)
Matched
142 (52.4)
29 (47.5)
0.660
Major mismatched
55 (20.3)
13 (21.3)
Minor mismatched
58 (21.4)
13 (21.3)
Major and minor mismatched
16 (5.9)
6 (9.9)
Median mononuclear cells, × 108/kg (range)
8.1 (4.6–13.2)
8.0 (5.2–11.4)
0.463
Median CD4+ counts, × 107/kg (range)
1.1 (0.1–4.2)
1.0 (0.2–2.3)
0.870
Median CD34+ counts, × 106/kg (range)
2.3 (0.5–8.2)
2.4 (0.3–7.6)
0.264
Previous broad-spectrum antibiotics before stool cultures, no. (%)
Carbapenem
91 (33.6)
22 (36.1)
0.711
Other β-lactam antibiotics
128 (47.2)
22 (36.1)
0.113
Tigecycline
8 (3.0)
4 (6.6)
0.244
Vancomycin/teicoplanin/linezolid
33 (12.2)
13 (21.3)
0.062
Multiple broad-spectrum antibiotics (≥2)
110 (40.6)
23 (37.7)
0.678
Oral mucositis during preconditioning treatment, no. (%)
None
223 (82.3)
53 (86.9)
0.647
Grades I to II
40 (14.8)
6 (9.8)
≥Grade III
8 (2.9)
2 (3.3)
Gastrointestinal tract toxicities during preconditioning treatment, no. (%)
≥Grade II
64 (23.6)
11 (18.0)
0.637
Cumulative dose of corticosteroid before stool cultures after haplo-HSCT, no. (prednisone, mg/kg)
4.9 (0.3–126.0)
5.1 (0.6–33.8)
0.483
Median duration of follow-up in survivors, day (range)
434 (61–765)
391 (64–756)
0.351
Tab.1
Type of organism
Number
Enterobacteriaceae
Escherichia coli
22
Klebsiella pneumoniae
4
Proteus mirabilis
2
Enterococcus
Enterococcus faecalis
5
Enterococcus faecium
9
Other bacteria
Pseudomonas aeruginosa
2
Streptococcus salivarius
1
Candida
Candida albicans
16
Candida parapsilosis
1
Candida glabrata
7
Candida tropicalis
1
Candida krusei
1
Saccharomyces cerevisiae
2
Tab.2
30-day neutrophil engraftment failure
100-day platelet engraftment failure
Hazard ratio (95% CI)
P
Hazard ratio (95% CI)
P
Microorganism in stool specimens
No
1.0
0.361
1.0
0.330
Yes
1.13 (0.86–1.53)
1.16 (0.86–1.57)
Enterobacteriaceae in stool specimens
No
1.0
0.201
1.0
0.871
Yes
1.33 (0.86–2.06)
0.96 (0.62–1.50)
Enterococcus in stool specimens
No
1.0
0.926
1.0
0.828
Yes
0.97 (0.57–1.67)
1.06 (0.61–1.86)
Candida in stool specimens
No
1.0
0.480
1.0
0.041
Yes
1.16 (0.77–1.74)
1.60 (1.02–2.50)
100-day grades II to IV aGVHD
100-day grades III to IV aGVHD
Hazard ratio (95% CI)
P
Hazard ratio (95% CI)
P
Microorganism in stool specimens
No
1.0
0.266
1.0
0.629
Yes
0.76 (0.47–1.24)
0.83 (0.39–1.77)
Enterobacteriaceae in stool specimens
No
1.0
0.077
1.0
0.279
Yes
0.45 (0.18–1.09)
0.46 (0.11–1.88)
Enterococcus in stool specimens
No
1.0
0.253
1.0
0.308
Yes
0.51 (0.16–1.61)
0.05 (0.01–16.98)
Candida in stool specimens
No
1.0
0.942
1.0
0.680
Yes
1.02 (0.54–1.96)
0.78 (0.24–2.52)
Tab.3
Fig.1
1-year relapse
1-year non-relapse mortality
1-year infection-related mortality
Hazard ratio (95% CI)
P
Hazard ratio (95% CI)
P
Hazard ratio (95% CI)
P
Microorganism in stool specimens
No
1.0
0.482
1.0
0.057
1.0
0.016
Yes
1.49 (0.49–4.53)
1.91 (0.98–3.72)
2.54 (1.19–5.43)
Enterobacteriaceae in stool specimens
No
1.0
0.484
1.0
0.397
1.0
0.368
Yes
0.05 (0.01–263.11)
1.56 (0.56–4.37)
1.73 (0.53–5.72)
Enterococcus in stool specimens
No
1.0
0.190
1.0
0.506
1.0
0.799
Yes
2.68 (0.62–11.65)
0.51 (0.07–3.71)
0.77 (0.11–5.67)
Candida in stool specimens
No
1.0
0.117
1.0
0.035
1.0
0.002
Yes
2.70 (0.78–9.34)
2.39 (1.06–5.38)
3.87 (1.66–9.03)
1-year disease-free survival
1-year overall survival
Hazard ratio (95% CI)
P
Hazard ratio (95% CI)
P
Microorganism in stool specimens
No
1.0
0.046
1.0
0.030
Yes
1.79 (1.01–3.17)
1.93 (1.07–3.51)
Enterobacteriaceae in stool specimens
No
1.0
0.893
1.0
0.658
Yes
1.07 (0.39–2.96)
1.26 (0.45–3.49)
Enterococcus in stool specimens
No
1.0
0.832
1.0
0.699
Yes
1.13 (0.36–3.62)
1.26 (0.39–4.03)
Candida in stool specimens
No
1.0
0.008
1.0
0.013
Yes
2.50 (1.27–4.92)
2.48 (1.21–5.07)
Tab.4
Outcome
HR (95% CI)
P value
Treatment failure as defined by overall survival
Candida in stool specimens
No
1
Yes
2.53 (1.22–5.24)
0.012
Disease risk index
Low risk
1
Intermediate risk
1.41 (0.59–3.38)
0.441
High risk
3.18 (1.19–8.47)
0.021
Very high risk
25.44 (6.91–93.73)
<0.001
Treatment failure as defined by disease-free survival
Candida in stool specimens
No
1
Yes
2.60 (1.31–5.18)
0.006
Disease risk index
Low risk
1
Intermediate risk
1.64 (0.69–3.89)
0.263
High risk
3.98 (1.53–10.37)
0.005
Very high risk
41.05 (11.02–152.95)
<0.001
Nonrelapse mortality
Candida in stool specimens
No
1
Yes
2.39 (1.06–5.38)
0.035
Infection-related mortality
Candida in stool specimens
No
1
Yes
3.87 (1.66–9.03)
0.002
Relapse
Disease risk index
Low risk
1
Intermediate risk
2.63 (0.34–20.37)
0.355
High risk
11.08 (1.33–92.05)
0.026
Very high risk
470.00 (37.69–5860.29)
<0.001
Tab.5
Fig.2
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