Among the 1380 patients with allogeneic HSCT in our center, a total of 311 (22.5%) patients were diagnosed with HC. HC was grade I, II, III, and IV in 84 (27.0%), 107 (34.4%), 73 (23.5%), and 47 patients (15.1%), respectively. Among these patients, 227 patients with HC of degree 2 or higher were included. Table 2 shows the demographic and clinical characteristics of these patients. The patients' primary diseases included acute myeloid leukemia (53, 23.3%), myelodysplastic syndrome (25, 11.0%), acute lymphoblastic leukemia (91, 40.1%), acute mixed cell leukemia (6, 2.6%), Hodgkin's lymphoma (3, 1.3%), aplastic anemia (32, 14.1%), T-cell lymphoma (1, 0.4%), and others (16, 7.0%).
Table 2
Patients of grade II and above characteristics
Number of patients | 227 |
Age (mean ± SD), years | 27.0 ± 14.5 |
Women, n (%) | 104(45.8%) |
Grade, n (%) II III IV | 107 (47.1%) 73 (32.2%) 47 (20.7%) |
Primary diseases, n (%) | |
Acute myeloid leukemia | 53 (23.3%) |
Myelodysplastic syndrome | 25 (11.0%) |
Acute lymphoblastic leukemia | 91 (40.1%) |
Acute mixed cell leukemia | 6 (2.6%) |
Hodgkin's lymphoma | 3 (1.3%) |
Aplastic anemia | 32 (14.1%) |
T-cell lymphoma | 1 (0.4%) |
Others | 16 (7.0%) |
CMV virus positivity, n (%) | 84(37.0%) |
EB virus positivity, n (%) | 35(16.3%) |
Cyclophosphamide exposure, n (%) | 201(88.5%) |
CBI failure | 39(17.2%) |
All the 227 patients with HC were treated with hydration, alkalization, diuretic, and other supportive therapy. When viremia was found, ganciclovir or sodium phosphonate was used for antiviral treatment and human immunoglobulin to enhance immunity treatment until the viremia turned negative. A total of 93 in 311 (29.9%) patients with severe hematuria were undergone CBI. Among 311 patients included, a total of 39 patients (12.5%) failed in CBI. Among them, 19 cases underwent cystoscopy to remove blood clots and urinary tract obstruction after failed manual flushing by experienced urologists, and 3 cases were transferred to the pediatric centers for cystoscopy due to their age.
2.1 Establishment of the cut-off value of the continuous variable
To determine the cutoff points of CRP, age, platelets count, post-transplantation onset time, serum albumin, and hemoglobin in the entire cohort, the ROC curve for CBI failure was plotted (Fig. 1). The area under the curve (AUC) of CRP was 0.784. The sensitivity and the specificity were 0.769 and 0.755 respectively as a CRP of 8.89 mg/dL was defined as the cutoff point. As for the onset time of HC after HSCT, the AUC was 0.773 and the cutoff value was determined as 37d by ROC curve, with a specificity of 0.660 and a sensitivity of 0.821. The cut-off values of age, platelet count, albumin, and hemoglobin were 14.5 years, 29.5 × 109/L, 36.05 g/L, and 83.5 g/L, respectively. Then the impact of CRP and other continuous variables were recoded into binary variables and evaluated in the univariate analysis according to the cutoff point,.
2.2 Univariate analysis of CBI failure (Table 3)
Table 3
Results of uni- and multivariate analyses
Variable | univariate analyses | | multivariate analyses |
| RR | P | 95%CI | | RR | P | 95%CI |
Age < 14.5 years | 2.746 | 0.005 | 1.322–5.702 | | 9.940 | 0.000 | 3.219–30.697 |
Male gender | 0.767 | 0.451 | 0.385–1.531 | | | | |
Haploidentical HSCT | 0.728 | 0.683 | 0.158–3.362 | | | | |
Gender difference | 0.965 | 0.926 | 0.454–2.052 | | | | |
Onset time of HC༞37d | 8.857 | 0.000 | 3.704–21.177 | | 7.021 | 0.001 | 2.204–22.364 |
platelet count༜29.5*109/L | 2.724 | 0.005 | 1.335–5.558 | | 1.892 | 0.186 | 0.736–4.862 |
Albumin༜36.05 g/L | 3.943 | 0.004 | 1.473–10.553 | | 2.377 | 0.145 | 0.741–7.623 |
CRP༞8.89 mg/dL | 10.290 | 0.000 | 4.551–23.264 | | 7.828 | 0.000 | 2.885–21.244 |
hemoglobin༜83.5 g/L | 3.010 | 0.002 | 1.468–6.172 | | 1.537 | 0.378 | 0.591–4.001 |
CMV positivity | 1.078 | 0.836 | 0.530–2.192 | | | | |
EB positivity | 1.415 | 0.434 | 0.591–3.385 | | | | |
Gender difference: Gender difference between donor and recipient |
In this study, among the 123 male patients, 19 (8.4%) were failed in CBI, compared with 20 among 104 female patients (8.8%). There was no correlation between gender and CBI failure (P = 0.451). The age in the whole cohort was 27.0 ± 14.5 (IQR 15–36 ) years. Among the 54 patients with age < 14.5 years, 16 (7.0%) failed in CBI, and among the 173 patients with age ≥ 14.5 years, 23 (70.4%) failed in CBI. Age < 14.5 years was significantly associated with CBI failure (RR = 2.746, 95% CI 1.322–5.702, P = 0.005).
In 227 patients, the onset time of HC after HSCT was right skewness, and the median and mean for the whole cohort was available for 33.0 d and 59.1 d (IQR 24.0 d-60.0 d). Among the 96 patients with an onset time of HC after HSCT more than 37 d, 32 (33.3%) underwent CBI failure. On the contrary, only 7 (5.3%) among the 131 patients with an onset time of HC after HSCT fewer than 37d failed in CBI. Onset time of HC after HSCT more than 37d was significantly associated with CBI failure in univariate analysis (RR = 8.857, 95% CI 3.704–21.177, P༜0.001).
In the study, the mean and median of CRP in the whole cohort were available for 12.08 mg/dL and 4.08 mg/dL (IQR 1.21–11.84). Among the 151 patients with CRP ≤ 8.89 mg/dL, 9 (5.96%) underwent CBI failure. Among the 76 patients with CRP༞8.89 mg/dL, 30 (39.47%) underwent CBI failure. CRP༞8.89 mg/dL was significantly associated with CBI failure (RR = 10.290, 95% CI 4.551–23.264, P༜0.005). In the univariate analysis palates count < 29.5 × 109/L (RR = 2.724, 95% CI 1.335–5.558, P = 0.005), albumin < 36.05 g/L (RR = 3.943, 95% CI 1.473–10.553, P = 0.004), and hemoglobin > 83.5 g/L (RR = 3.010, 95% CI 1.468–6.172, P = 0.002) were also significantly associated with CBI failure.
Nevertheless, in the univariate analysis gender difference between donor and recipient, primary disease type, haploidentical HSCT, CMV positivity, and EB positivity (P > 0.05).
2.2 Multivariate analysis of CBI failure (Table 3)
In multivariate analysis, CRP > 8.89 ng/ml (RR = 7.828, 95% CI 2.885–21.244, P < 0.001), age < 14.5 years (RR = 9.940, 95% CI 3.219–30.697, P < 0.001), and onset time of HC༞37d after transplantation (RR = 7.021, 95% CI 2.204–22.364, P = 0.001) were independent risk factors for failure of CBI.