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Interaction between High-Dose Intravenous Busulfan and Post-Transplant Cyclophosphamide on Hemorrhagic Cystitis after Allogeneic Hematopoietic Cell Transplantation
Carreira, A. S., Salas, M. Q., Remberger, M., Novitzky-Basso, I., Law, A. D., Lam, W., Pasic, I., Mazzulli, T., Cserti-Gazdewich, C., Kim, D. D. H., et al
Transplantation and cellular therapy. 2023
Abstract
This study investigates the incidence and predictors of hemorrhagic cystitis (HC) in 960 adults undergoing allo-HSCT. Two-hundred and fifty-two (26.5%) patients received MAC regimens, and 81.4% received high-dose IV busulfan (HD Bu). Six-hundred and ninety-five (72.4%) patients received PTCY-based prophylaxis, and 91.4% additionally received ATG and CsA (PTCY-ATG-CsA). 228 (23.8%) patients developed HC. The day +100 cumulative incidences of grades 2-4 and 3-4 HC were 11.1% and 4.9%. BK virus was isolated in 58.3% of urinary samples. Using HD BU myeloablative regimens increased the risk for grade 2-4 HC (HR 1.97, P=0.035), and HD BU combined with ATG-PTCY-CsA increased this four times (HR 4.06, HR<0.001) for grade 2-4 HC compared to patients who received neither of these drugs. A significant correlation was documented between grade II-IV aGVHD and grade 2-4 HC (HR 2.10, P<0.001). Moreover, patients with BK-POS grade 2-4 HC had lower 1-year OS (HR 1.51, P=0.009) and higher NRM (HR 2.31, P<0.001), and patients with BK-NEG grade 2-4 HC had comparable post-transplant outcomes. In conclusion, intravenous HD Bu was identified as a predictor for grade 2-4 HC. Moreover, when HD Bu was combined with PTCY-ATG-CsA, the risk increased four-fold. Based on the results provided by this study, preventing the onset of HC, especially in high-risk patients, is mandatory as its presence significantly increases the risk for mortality.
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Outpatient haploidentical hematopoietic stem cell transplant using post-transplant cyclophosphamide and incidence of hemorrhagic cystitis
Gutiérrez-Aguirre, C. H., Esparza-Sandoval, A. C., Palomares-Leal, A., Jaime-Pérez, J. C., Gómez-Almaguer, D., Cantú-Rodríguez, O. G.
Hematology, transfusion and cell therapy. 2020
Abstract
INTRODUCTION Hemorrhagic cystitis (HC) is a common complication of haploidentical hematopoietic stem cell transplantation (haplo-HSCT), characterized by irritative symptoms of the urinary tract and a higher morbidity and mortality rate. The worldwide incidence is reported between 10% and 70%. The use of alkylating agents and BK viral infection are the most frequent etiologies. The aim of this study was to report the HC incidence in an outpatient haplo-HCST program with a reduced intensity-conditioning (RIC) regimen, cataloguing risk factors, complications and final outcomes. METHODS The medical database of patients who received a haplo-HSCT between January 2012 and November 2017 was retrospectively analyzed. Demographic variables, general characteristics and HC incidence were included. RESULTS One hundred and eleven patients were included, 30 (27%) of whom developed HC, most of them (70%) being grade II, with a 30-day (7-149) median time of post-transplant HC onset. The BK virus was detected in 71% of the urine samples analyzed. All HC patients responded to treatment, except two (6.6%), who died due to HC complications. CONCLUSIONS There was no difference in the HC incidence or severity, compared to that reported when performing haplo-HSCT in hospitalized patients, although the donor-recipient sex mismatch did relate to a higher HC incidence.
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Incidence and risk factor of hemorrhagic cystitis after allogeneic transplantation with fludarabine, busulfan, and anti-thymocyte globulin myeloablative conditioning
Lam, W., Storek, J., Li, H., Geddes, M., Daly, A.
Transplant Infectious Disease. 2017;19(3)
Abstract
BACKGROUND Hemorrhagic cystitis (HC) is a complication of allogeneic stem cell transplantation (SCT), associated with factors such as BK polyomavirus reactivation, age, conditioning regimen, and presence of graft-versus-host disease (GVHD). The incidence and impact of HC in patients receiving fludarabine (Flu), busulfan (Bu), and anti-thymocyte globulin (ATG) conditioning is unknown. METHODS We conducted a case-control study of patients undergoing SCT at our center between January 1, 2003 and Dec 31, 2012, to determine the incidence of HC and its effect on patient outcomes including overall survival (OS), relapse, non-relapse mortality (NRM), GVHD, and healthcare resource use. RESULTS In total, 94 cases of HC were identified and matched to controls based on age, donor type, disease type, and disease status at transplantation. The total incidence of HC was 17.7% (117 of 661 patients). Cases had a higher rate (43.6% vs 27.1%, P=.0394) of acute GVHD (Grade II-IV), and chronic GVHD requiring systemic steroids (34.9% vs 18.6%, P=.004). Male gender was found to be a risk factor (hazard ratio [HR]=1.725, P=.017). OS and progression-free survival did not differ between cases and controls (OS HR=1.128, 95% confidence interval [CI] 0.7807-1.639; progression-free survival HR=0.8809, 95% CI 0.6320-1.234), however the rate of NRM was higher in cases (HR=1.632, 95% CI 1.007-2.830). Median length of hospitalization was longer for patients with HC than matched controls (65.5 days vs 40.5 days, P<.0001). CONCLUSION HC is common in patients undergoing allogeneic SCT with FluBuATG conditioning, and affects the duration of hospitalization. Rate of GVHD is higher among patients with HC. While OS is not affected, an association was seen with higher NRM in our study. Improvement in treatment for HC may lead to reductions in morbidity and healthcare resource utilization. Copyright © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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Continuous IV infusion of MESNA can prevent hemorrhagic cystitis in HSCT and retain MESNA concentration in urine
Jiang, Q., Huang, H., Liu, Q., Sun, J., Zhou, H., Fan, Z., Zhang, Y., Huang, F., Chai, Y., Xu, D., et al
Bone Marrow Transplantation. 2015;50(11):1490-2