Hemorrhagic cystitis following high-dose chemotherapy and bone marrow transplantation in children with malignancies: incidence, clinical course, and outcome.

Brugières, L; Hartmann, Olivier; Travagli, J. P.; Benhamou, E; Pico, J. L.; Valteau, D; Kalifa, Chantal; Patte, Catherine; Flamant, F; Lemerle, J

doi:10.1200/jco.1989.7.2.194

Cited by 106 publications

(113 citation statements)

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“…26 SOS has already been linked to the administration of HD Bu, and its severity can be increased by Cyclophosphamide-containing regimens. 41,42 Importantly, we observed that the duration of SOS decreased over time, and this was probably related to better supportive care and rigorous management of drugs to avoid additional toxicity associated with drug interactions and additive toxic effects on visceral organs. Very few patients had to be transferred to an Intensive Care Unit.…”

Section: Discussionmentioning

confidence: 88%

Busulfan–melphalan in high-risk neuroblastoma: the 30-year experience of a single institution

Pasqualini

Blanchard

et al. 2016

Bone Marrow Transplant

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High-dose chemotherapy (HDC) was investigated in high-risk neuroblastoma (HR-NBL) to reduce the risk of relapse. We report the results of the 30-year experience of a cohort of patients with HR-NBL treated with high-dose (HD) busulfan (Bu)-containing regimens. From 1980From to 2009 patients aged 41 year with stage 4 NBL were treated with HD Bu-containing regimens at Gustave Roussy. These data were prospectively recorded in the Pediatric Transplantation Database. The median age at diagnosis was 40 months (12-218 months). All patients had a stage 4 neuroblastoma. NMYC amplification was displayed in 24% of the tumors. The hematopoietic support consisted of bone marrow or PBSCs in 46% and 49% of patients, respectively. The 5-year eventfree survival and overall survival rates of the whole cohort were 35.1% and 40%, respectively. Age at diagnosis, bone marrow involvement and tumor response after induction chemotherapy were significant prognostic factors. Toxicity was manageable and decreased over time, owing to both PBSC administration and better supportive care. Based on this experience, HD Bu-melphalan (Mel) has been implemented in Europe and compared with Carboplatin-Etoposide-Mel in the European SIOP Neuroblastoma (SIOPEN)/HR-NBL randomized protocol. It has now become the standard HDC in the SIOPEN HR strategy. INTRODUCTIONThe improved survival rates of patients with high-risk (HR) neuroblastoma (NBL) observed during the past decades are related to the intensification of induction therapy, high-dose chemotherapy (HDC) and better supportive care. 1 In the HR-NBL population, a correlation between survival and dose intensity has been reported, and three randomized studies showed that HDC followed by autologous stem cell transplantation (ASCT) or autologous bone marrow transplantation (ABMT) improved survival rates. [2][3][4] As NBL is notoriously radiosensitive, hyperfractionated TBI was incorporated into the conditioning regimen and has yielded encouraging results. 5 Alkylating agents were demonstrated to produce a log-linear dose response against tumor cells in vitro. 6 Since the mid-1980s, HDC with alkylating agents and ASCT has been the treatment strategy used at Gustave Roussy. HD busulfan (Bu) was selected because of its specific cytotoxicity against quiescent cells, 7 as an alternative to TBI in HR-NBL patients to avoid its side-effects, 8 especially in this very young population, and to achieve better survival rates.We report here the results of our 30-year experience on patients with HR-NBL treated with HD Bu-containing regimens. Bu was combined with melphalan (Mel) or Mel plus cyclophosphamide, and HDC was followed by stem cell (SC) or bone marrow (BM) transplantation. These results provided the rationale to widely implement the use of HD Bu-Mel, which was then compared with Carboplatin-Etoposide-Mel (CEM) in the European SIOP Neuroblastoma (SIOPEN)/HR-NBL randomized trial. HD Bu-Mel has now become the standard HD regimen in the SIOPEN HR strategy.

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Section: Discussionmentioning

confidence: 88%

Busulfan–melphalan in high-risk neuroblastoma: the 30-year experience of a single institution

Pasqualini

Blanchard

et al. 2016

Bone Marrow Transplant

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“…36 Many studies have tried to identify the risk factors for BK-HC in allo-HSCT. 1,3,4,10,23,24,28,31,32,37 Older age was identified as a risk factor in pediatric HSCTs, 2,3,31 but no other risk factor has been consistently verified in adult HSCTs, although aGVHD, BU-based conditioning regimens, the type of HSCT and the intensity of conditioning have been suggested. 4,10,23,24,26,30,32 Most recently, Rorije et al 4 reported a single-center, retrospective study.…”

Section: Discussionmentioning

confidence: 99%

“…[1][2][3][4][5][6] While early-onset HC is usually mild with microscopic hematuria and secondary to the chemoradiation (e.g., CY), more severe HC with gross hematuria develops in the later course of allo-HSCT (⩾30 days after transplant) and is strongly associated with BK virus. 1,3,[7][8][9][10][11][12] Polyomavirus BK (BKV) is a double-stranded non-enveloped DNA virus first isolated from a urine sample obtained from a renal transplant recipient.…”

Section: Introductionmentioning

confidence: 99%

The risk of polyomavirus BK-associated hemorrhagic cystitis after allogeneic hematopoietic SCT is associated with myeloablative conditioning, CMV viremia and severe acute GVHD

Uhm

Hamad

Michelis

et al. 2014

Bone Marrow Transplant

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Hemorrhagic cystitis (HC) is a common complication after allogeneic hematopoietic SCT (allo-HSCT). Several risk factors have been suggested including BU-containing myeloablative conditioning, unrelated donors and GVHD, but these have not been consistently reported. We conducted a retrospective study including 339 allo-HSCT recipients between 2009 and 2012. Of 339 patients, 79 (23.3%) developed HC with 2-year cumulative incidence of 24.0% (95% confidence interval, 19.4-28.9). The median onset time was 45 days (range, 16-430) after allo-HSCT. Sixty-two patients (84%) out of 74 evaluated for urine BK virus PCR testing showed a positive result (mean 2.0 × 10 10 copies of DNA per mL). In univariate analysis, myeloablative conditioning, HLA-mismatched donor, CMV viremia and acute GVHD (aGVHD) grade 3-4 were significantly associated with the risk of HC. Multivariate analysis confirmed all associating factors identified in univariate analysis except for HLA-mismatched donor: myeloablative conditioning (hazard ratio (HR) 2.63, P = 0.003), CMV viremia (HR 1.88, P = 0.014) and aGVHD grade 3-4 (HR 1.71, P = 0.029). HC did not affect OS or non-relapse mortality. Symptomatic HC is a frequent complication following allo-HSCT, with a 2-year cumulative incidence of 24.0%. Three clinical factors associated with HC were identified including myeloablative conditioning, CMV viremia and severe aGVHD.

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“…A wide variety of causal factors can give rise to posttransplant hemorrhagic cystitis (PTHC) as these patients are on various immunosuppressive medications for prevention/therapy of GVHD. The incidence of PTHC among the BMT recipients ranges from 6.5 to 52 % [1,2]. It is characterized by the classical symptoms of lower urinary tract symptoms like dysuria, haematuria, urgency and increased frequency.…”

Section: Discussionmentioning

confidence: 99%

“…Renal parameters were within normal limits. A working diagnosis of grade III hemorrhagic cystitis (HC) was made as per criteria mentioned in Table 2 [1]. Urine culture was negative for bacterial pathogens, therefore the possibility of single or combined opportunistic viral infections as a cause of HC was suspected in view of ongoing immunosuppression.…”

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confidence: 99%

A Rare Case of Hemorrhagic Cystitis in Allogeneic Hematopoietic Stem Cell Transplant Patient

Sahu

Prakash

Khadwal

et al. 2015

Indian J Hematol Blood Transfus

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Post bone marrow transplant patients are susceptible to atypical infections, especially viral pathogens. The risk increases many folds in cases of allogeneic transplantation, which also receive GVHD prophylaxis. Viral pathogens like cytomegalovirus and herpes are the common ones encountered during follow-up period. However, in recent times there have been reports of a variety of disease manifestations of rare viruses like polyoma virus and adenovirus. These viral infections may play a crucial role in morbidity and mortality in immunocompromised patients. We hereby elaborate the follow-up course of a 36-year-old post allogeneic transplant patient of acute myeloid leukemia who developed adenovirus related haemorrhagic cystitis. Treatment with oral ribavirin lead to dramatic improvement in symptomatology within a week. This cases re-emphasizes the fact that after ruling out the commoner pathogens, it's of utmost importance to strongly consider the atypical pathogens in such cases. Case-ReportA 36-year-old gentleman, known case of acute myeloid leukemia (FAB-M2) was admitted on Day ?380 of allogeneic stem cell transplant with 7 days history of lower urinary tract symptoms (LUTS), dysuria, increased urine frequency, urgency of urine, and haematuria. In the background, patient received inj. busulphan (0.8 mg/kg every 6 h for 4 days) and inj. cyclophosphamide (60 mg/kg/day for 2 days) as conditioning regimen. Peri-transplant period was unremarkable for any complication. No features of high dose cyclophosphamide induced cystitis or acute graft versus host disease (aGVHD) was noted. He received cyclosporine-A (5 mg/m 2 ) and methotrexate 15 mg/m 2 on Day ?1 and 10 mg/m 2 on Day ?3, ?6 and ?11 as prophylaxis for GVHD (Fig. 1). Tapering of immunosuppression was started on Day ?80 onwards and patient did not have any evidence of GVHD till Day ?256. Following which he developed lichenoid changes in the oral mucosa, dryness of eyes and hypopigmented patches over the face and upper trunk involving \25 % of body surface (Fig. 2). Liver function tests showed total bilirubin levels-1.2 g/dL, SGOT, SGPT and SALP of 92, 139, 392 IU/mL, respectively. After clinical examination, laboratory evaluation and liver?skin biopsy he was diagnosed as moderate cGVHD (Table 1). As a result additional immunosuppressive medications in the form of mycophenolate (1000 mg BD) along with oral prednisolone was started. He also received topical cyclosporine eye drops (0.05 %) for conjunctival GVHD. Following immunosuppressive therapy symptoms related to GVHD started improving (Fig.

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Hemorrhagic cystitis following high-dose chemotherapy and bone marrow transplantation in children with malignancies: incidence, clinical course, and outcome.

Cited by 106 publications

References 22 publications

Busulfan–melphalan in high-risk neuroblastoma: the 30-year experience of a single institution

Busulfan–melphalan in high-risk neuroblastoma: the 30-year experience of a single institution

The risk of polyomavirus BK-associated hemorrhagic cystitis after allogeneic hematopoietic SCT is associated with myeloablative conditioning, CMV viremia and severe acute GVHD

A Rare Case of Hemorrhagic Cystitis in Allogeneic Hematopoietic Stem Cell Transplant Patient

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