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Frontiers of Medicine

Front. Med.    2019, Vol. 13 Issue (4) : 492-503
Positive stool culture could predict the clinical outcomes of haploidentical hematopoietic stem cell transplantation
Lijuan Hu1, Qi Wang4, Xiaohui Zhang1, Lanping Xu1, Yu Wang1, Chenhua Yan1, Huan Chen1, Yuhong Chen1, Kaiyan Liu1, Hui Wang4, Xiaojun Huang1,2,3, Xiaodong Mo1()
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
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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.

Keywords haploidentical      hematopoietic stem cell transplantation      stool culture      Candida     
Corresponding Authors: Xiaodong Mo   
Just Accepted Date: 01 March 2019   Online First Date: 08 April 2019    Issue Date: 02 August 2019
 Cite this article:   
Lijuan Hu,Qi Wang,Xiaohui Zhang, et al. Positive stool culture could predict the clinical outcomes of haploidentical hematopoietic stem cell transplantation[J]. Front. Med., 2019, 13(4): 492-503.
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Lijuan Hu
Qi Wang
Xiaohui Zhang
Lanping Xu
Yu Wang
Chenhua Yan
Huan Chen
Yuhong Chen
Kaiyan Liu
Hui Wang
Xiaojun Huang
Xiaodong Mo
Variable Negative stool cultures group (n = 271) Positive stool cultures group (n = 61) P value
Gender of patients, male/female 161/110 34/27 0.599
Median age at transplantation, year (range) 30 (2–67) 27 (7–63) 0.123
Adult/children 227/44 52/9 0.775
Diagnosis, no. (%)
Acute myeloid leukemia 106 (39.1) 20 (32.8) 0.773
Acute lymphoblastic leukemia 76 (28.0) 20 (32.8)
Myelodysplastic syndrome 37 (13.7) 10 (16.4)
Severe aplastic anemia 32 (11.8) 5 (8.2)
Chronic myeloid leukemia 6 (2.2) 2 (3.2)
Others 14 (5.2) 4 (6.6)
Chemotherapy before HSCT, no. (%) 198 (73.1) 45 (73.8) 0.910
Median cycles before HSCT, no. (range) 4 (1–18) 4 (1–14) 0.228
Disease status at transplantation, no. (%)
Standard risk 259 (95.6) 61 (100.0) 0.133
High risk 12 (4.4) 0 (0.0)
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  Patient characteristics
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  Microorganisms in stool specimens
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  Effect of PSCs on the engraftment and aGVHD
Fig.1  Clinical outcomes of patients who underwent haplo-HSCT on the basis of the results of stool cultures. (A) relapse, (B) non-relapse mortality, (C) infection-related mortality, (D) overall survival, and (E) disease-free survival. NSC, negative stool cultures; PSC, positive stool cultures.
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  Effect of PSCs on relapse, nonrelapse mortality, and survival
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
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  Multivariate analysis of risk factors of clinical outcomes
Fig.2  Survival of haplo-HSCT recipients with and without Candida in stool specimens. (A) Infection-related mortality, (B) overall survival, and (C) disease-free survival.
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