Risk factors for severe hemorrhagic cystitis following BMT

Seber, Adriana; Shu, Xiao Ou; DeFor, Todd E.; Sencer, Susan; Ramsay, Norma K.C.

doi:10.1038/sj.bmt.1701523

Cited by 155 publications

(160 citation statements)

References 26 publications

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“…BU has been implicated as a risk factor for HC but a dose-dependent correlation has not been reported. 10,[37][38][39] In this study, the subgroup analysis including fludarabine/BU/TBI conditioning showed myeloablative conditioning regimen as a risk factor for HC in multivariate analysis. This analysis could support the dose dependence of BU on the development of BK-HC as Gilis et al 28 suggested a conditioning regimen including 4 days of BU for a risk factor for BK-HC.…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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“…Moreover, the ubiquitous use of BU may also explain the lack of difference as other studies have proven BU to be a risk factor of HC development. [24][25][26] As the urinary tract is the main site of BKV latency, it is expected to be the first site of reactivation. Transient BK viruria occurs in all allo-HSCT patients 19 with 4-25% of the patients developing sustained BKV-HC.…”

Section: High Burden Of Bk Virus-associated Hemorrhagic Cystitis L Gimentioning

confidence: 99%

“…Transient BK viruria occurs in all allo-HSCT patients 19 with 4-25% of the patients developing sustained BKV-HC. 8,15,17,19,20,[26][27][28][29] A peak in BK viruria X3 to 6-log correlates with the occurrence of HC. 1,18,29,30 Consistent with these data, all the patients in our study had a BK viruria higher than 10 8 copies/mL indicating that BK viruria may not be the most relevant factor for the prediction of BKV-HC severity.…”

Section: High Burden Of Bk Virus-associated Hemorrhagic Cystitis L Gimentioning

confidence: 99%

High burden of BK virus-associated hemorrhagic cystitis in patients undergoing allogeneic hematopoietic stem cell transplantation

Gilis

Morisset

Billaud

et al. 2014

Bone Marrow Transplant

120

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on behalf of the Lyon BK virus Study group 5 BK virus (BKV) reactivation has been increasingly associated with the occurrence of late-onset hemorrhagic cystitis (HC) after allogeneic hematopoietic SCT (allo-HSCT) resulting in morbidity and sometimes mortality. We investigated the incidence, risk factors and outcome of BKV-HC in 323 consecutive adult patients undergoing allo-HSCT over a 5-year period. BK viremia values for HC staging were evaluated, as well as the medico-economic impact of the complication. Forty-three patients developed BKV-HC. In univariate analysis, young age (P ¼ 0.028), unrelated donor (P ¼ 0.0178), stem cell source (P ¼ 0.0001), HLA mismatching (P ¼ 0.0022) and BU in conditioning regimen (P ¼ 0.01) were associated with a higher risk of developing BKV-HC. In multivariate analysis, patients receiving cord blood units (CBUs) (P ¼ 0.0005) and peripheral blood stem cells (P ¼ 0.011) represented high-risk subgroups for developing BKV-HC. BK viremia was directly correlated to HC severity (P ¼ 0.011) with a 3 to 6-log peak being likely associated with grades 3 or 4 HC. No correlation was found between BKV-HC and acute graft versus host disease or mortality rate. Patients with BKV-HC required a significantly longer duration of hospitalization (Po0.0001), more RBC (P ¼ 0.0003) and platelet transfusions (Po0.0001). Over the 5-year study period, the financial cost of the complication was evaluated at h2 376 076 ($3 088 899). Strategies to prevent the occurrence of late-onset BKV-HC after allo-HSCT are urgently needed, especially in CBU and peripheral blood stem cell recipients. BK viremia correlates with the severity of the disease. Prospective studies are required to test prophylactic approaches.

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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%

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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Risk factors for severe hemorrhagic cystitis following BMT

Cited by 155 publications

References 26 publications

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

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

High burden of BK virus-associated hemorrhagic cystitis in patients undergoing allogeneic hematopoietic stem cell transplantation

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

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