Kidney and Bladder Complications of Hematopoietic Cell Transplantation

Hingorani, Sangeeta

doi:10.1002/9781118416426.ch96

Cited by 4 publications

(3 citation statements)

References 164 publications

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“…The threshold for pre‐emptive therapy with rituximab was greater than or equal to 5,000 copies/mL. Hemorrhagic cystitis (HC) was defined as the presence of hematuria, symptomatic or asymptomatic and was graded as follows: grade I, microscopic; grade II, macroscopic; grade III, with clots; and grade IV, requiring instrumentation for clot evacuation or leading to urinary retention or requiring surgical intervention . The diagnosis and grading of graft‐versus‐host disease (GvHD) were based on consensus criteria and biopsies were performed when possible.…”

Section: Methodsmentioning

confidence: 99%

Epidemiology of viral infections among children undergoing hematopoietic stem cell transplant: Α prospective single‐center study

Tsoumakas

Giamaiou

Goussetis

et al. 2019

Transplant Infectious Dis

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Background: Viral infections are a significant cause of morbidity and mortality in pediatric transplant populations. We analyzed the epidemiology of viral infections in pediatric hematopoietic stem cell transplant (HSCT) patients, including their incidence, associated risk factors, and outcome. Methods:In a prospective study from September 2011 to September 2015, blood, urine, and stool specimens were monitored weekly from transplantation to day 100 or after if clinically suspected, by use of real-time polymerase chain reaction. Cytomegalovirus (CMV), Epstein-Barr virus (EBV), BK polyomavirus (BKV), Herpes simplex virus-1,2, Varicella zoster virus, Human herpes virus-6,7, and Adenovirus infections were monitored. All children and adolescents who underwent HSCT received long-term follow up in the regular outpatient clinics (range 2-48 months). Results: A total of 192 HSCTs (autologous/allogeneic: 53/139) were performed in 165 subjects (median age: 5.6 years). Viruses most commonly isolated were CMV (46.1%), BKV (25.9%) and EBV (22.6%) and were more frequent in allogeneic versus autologous transplants (P < 0.05). Almost all high-risk allogeneic recipients developed EBV infections post-HSCT. EBV-PTLD was the only cause of death among those who developed viral disease. The factors significantly associated with the development of viral infections were recipient's advanced age, unrelated donor, mismatched graft and use of peripheral blood stem cells grafts. Conclusions: Viral infections were common among our pediatric recipients. Data suggest that monitoring of viral load may be significant to the prevention of viral disease. Particular demographic and transplantation characteristics were associated with the development of viral infections post-HSCT. K E Y W O R D S viral infections, hematopoietic stem cell transplant, risk factors, children

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Section: Methodsmentioning

confidence: 99%

Epidemiology of viral infections among children undergoing hematopoietic stem cell transplant: Α prospective single‐center study

Tsoumakas

Giamaiou

Goussetis

et al. 2019

Transplant Infectious Dis

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“…HC was graded according to the criteria described previously (Hingorani, 2009): grade I = microscopic hematuria, grade II = macroscopic hematuria, grade III = macroscopic hematuria with clots, and grade IV = macroscopic hematuria with clot needing instrumentation for clot evacuation or leading to urinary retention or requiring surgical intervention.…”

Section: Methodsmentioning

confidence: 99%

The Association of Combined GSTM1 and CYP2C9 Genotype Status with the Occurrence of Hemorrhagic Cystitis in Pediatric Patients Receiving Myeloablative Conditioning Regimen Prior to Allogeneic Hematopoietic Stem Cell Transplantation

et al. 2017

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Hemorrhagic cystitis (HC) is one of the complications of busulfan-cyclophosphamide (BU-CY) conditioning regimen during allogeneic hematopoietic stem cell transplantation (HSCT) in children. Identifying children at high risk of developing HC in a HSCT setting could facilitate the evaluation and implementation of effective prophylactic measures. In this retrospective analysis genotyping of selected candidate gene variants was performed in 72 children and plasma Sulfolane (Su, water soluble metabolite of BU) levels were measured in 39 children following treatment with BU-CY regimen. The cytotoxic effects of Su and acrolein (Ac, water soluble metabolite of CY) were tested on human urothelial cells (HUCs). The effect of Su was also tested on cytochrome P 450 (CYP) function in HepaRG hepatic cells. Cumulative incidences of HC before day 30 post HSCT were estimated using Kaplan–Meier curves and log-rank test was used to compare the difference between groups in a univariate analysis. Multivariate Cox regression was used to estimate hazard ratios with 95% confidence intervals (CIs). Multivariate analysis included co-variables that were significantly associated with HC in a univariate analysis. Cumulative incidence of HC was 15.3%. In the univariate analysis, HC incidence was significantly (p < 0.05) higher in children older than 10 years (28.6 vs. 6.8%) or in children with higher Su levels (>40 vs. <11%) or in carriers of both functional GSTM1 and CYP2C9 (33.3 vs. 6.3%) compared to the other group. In a multivariate analysis, combined GSTM1 and CYP2C9 genotype status was associated with HC occurrence with a hazards ratio of 4.8 (95% CI: 1.3–18.4; p = 0.02). Ac was found to be toxic to HUC cells at lower concentrations (33 μM), Su was not toxic to HUC cells at concentrations below 1 mM and did not affect CYP function in HepaRG cells. Our observations suggest that pre-emptive genotyping of CYP2C9 and GSTM1 may aid in selection of more effective prophylaxis to reduce HC development in pediatric patients undergoing allogeneic HSCT.Article summary:(1) Children carrying functional alleles in GSTM1 and CYP2C9 are at high risk for developing hemorrhagic cystitis following treatment with busulfan and cyclophosphamide based conditioning regimen.(2) Identification of children at high risk for developing hemorrhagic cystitis in an allogeneic HSCT setting will enable us to evaluate and implement optimal strategies for its prevention.Trial registration: This study is a part of the trail “clinicaltrials.gov identifier: NCT01257854.”

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“…All four patients developed severe HC defined as symptoms of cystitis together with hematuria grade III–IV . HC manifested as severe bleeding with clots and severe abdominal pain requiring intensive transfusion support and opiate analgesia.…”

Section: Patients and Treatmentmentioning

confidence: 99%

Intravesical cidofovir to treat BK virus‐associated hemorrhagic cystitis in children after hematopoietic stem cell transplantation

Rascon

Verkauskas

Pasaulienė

et al. 2015

Pediatric Transplantation

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HC related to BK virus replication might be a severe complication following allogeneic HSCT. There are no clearly defined treatment guidelines in pediatric population. The data on the effectiveness of ICI to manage severe bleeding in children are very limited. We report our experience of intravesical cidofovir in four children, 6-15 yr of age, to manage grade III-IV BK virus-associated HC. Three of four children had high CSA serum level prior to developing cystitis. Intravesical instillations of cidofovir resulted only in temporal relief of bleeding. After immune suppression was withdrawn or tapered, intravesical instillations of formalin solution had to be undertaken to abort severe bleeding. We concluded that intravesical cidofovir alone did not appear to be sufficiently effective in case of severe HC, necessitating complimentary procedures to stop macrohematuria.

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Kidney and Bladder Complications of Hematopoietic Cell Transplantation

Cited by 4 publications

References 164 publications

Epidemiology of viral infections among children undergoing hematopoietic stem cell transplant: Α prospective single‐center study

Epidemiology of viral infections among children undergoing hematopoietic stem cell transplant: Α prospective single‐center study

The Association of Combined GSTM1 and CYP2C9 Genotype Status with the Occurrence of Hemorrhagic Cystitis in Pediatric Patients Receiving Myeloablative Conditioning Regimen Prior to Allogeneic Hematopoietic Stem Cell Transplantation

Intravesical cidofovir to treat BK virus‐associated hemorrhagic cystitis in children after hematopoietic stem cell transplantation

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