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CLINICAL ASSESSMENT OF PATHOGENETIC VIRUSES IN HEMORRHAGIC CYSTITIS AFTER ALLOGENEIC CELL TRANPLANTATION: HOW HIGH IS HIGH FOR URINE BK POLYOMA VIRAL LOAD.
Author(s): ,
Apostolia Papalexandri
Affiliations:
Hematology Department and HCT Unit,G.Papanikolaou Hospital,Thessaloniki,Greece
,
Despina Mallouri
Affiliations:
Hematology Department and HCT Unit,G.Papanikolaou Hospital,Thessaloniki,Greece
,
Varnavas Konstantinou
Affiliations:
Hematology Department and HCT Unit,G.Papanikolaou Hospital,Thessaloniki,Greece
,
Panayota Zerva
Affiliations:
Hematology Department and HCT Unit,G.Papanikolaou Hospital,Thessaloniki,Greece
,
Evdoxia Koravou
Affiliations:
Hematology Department and HCT Unit,G.Papanikolaou Hospital,Thessaloniki,Greece
,
Maria Kalliou
Affiliations:
Hematology Department and HCT Unit,G.Papanikolaou Hospital,Thessaloniki,Greece
,
Ioannis Batsis
Affiliations:
Hematology Department and HCT Unit,G.Papanikolaou Hospital,Thessaloniki,Greece
,
Evangelia Yannaki
Affiliations:
Hematology Department and HCT Unit,G.Papanikolaou Hospital,Thessaloniki,Greece
,
Tasoula Touloumenidou
Affiliations:
Hematology Department and HCT Unit,G.Papanikolaou Hospital,Thessaloniki,Greece
,
Christos Smias
Affiliations:
Hematology Department and HCT Unit,G.Papanikolaou Hospital,Thessaloniki,Greece
,
Achilles Anagnostopoulos
Affiliations:
Hematology Department and HCT Unit,G.Papanikolaou Hospital,Thessaloniki,Greece
Ioanna Sakellari
Affiliations:
Hematology Department and HCT Unit,G.Papanikolaou Hospital,Thessaloniki,Greece
(Abstract release date: 05/19/16) EHA Library. Papalexandri A. 06/09/16; 135065; PB2165
Ms. Apostolia Papalexandri
Ms. Apostolia Papalexandri
Contributions
Abstract
Abstract: PB2165

Type: Publication Only

Background
Hemorrhagic cystitis (HC) after allogeneic hematopoetic cell transplantation (allo-HCT) has been recognized to be a relatively common severe complication with increased morbidity requiring hospitalization. Apart from conditioning toxicity, the most common pathogens implicated are cytomegalovirus (CMV) and BK-polyoma virus (BKPV). Data concerning the clinical relevance of molecular monitoring of these viruses in urine are scarce. 

Aims
We conducted a retrospective study enrolling patients who developed cystitis after allo-HCT to evaluate the urine viral load of both CMV and BKV that is potentially associated with HC . 

Methods
CMV and BKPV viral load in urine and CMV in plasma were measured with RQ-PCR in symptomatic patients with cystitis. Macroscopic hematuria (+/-clots) led to the diagnosis of hemorrhagic cystitis. 

Results
Twenty-nine patients (female=14, male=15), aged 16-61 years (median 35) who developed cystitis after allo-HCT and for who viral load data were available for both pathogens were included in the study. Patients suffered from hematological malignancies and underwent allo-HCT following myeloablative (21) or reduced intensity conditioning regimen (8). The majority of patients (17/29) received graft from a matched volunteer, 8/29 from siblings and 4 from a haplo-identical relative donor. Median time for the onset of cystitis was 48 days (7-677). Fourteen out of 29 (48%) patients experienced HC requiring hospitalization. CMV viral load in urine was positive in 7/29 samples (median: 1270 copies/ml, range: 180-1490000). Concordant CMV viremia was documented in 15 patients (median: 2570 copies/ml, range: 26-81000). BKPV viral load in urine was positive in 23/29 patients (median 2,5x107 copies/ml, range: 1,18x102-3,2x1010). Bacterial infection by klebsiella pneumonia was documented in one patient. Hemorrhagic cystitis was significantly associated with BKPV viral load: 2,5x107 in HC patients vs 1,9x104 in non-HC, p=0.018. A cut- off of 5,1x104 copies/ml could strongly predict the development of hematuria in ROC analysis. CMV viral load in urine and plasma tended to be higher in HC patients without a significant difference: (i) in urine: 106575 vs 523 copies/ml and (ii) in plasma: 9004 vs 2584 copies/ml for HC vs non-HC patients respectively, p=ns. No other clinical or biological factors could predict the development of HC. Cytology was available in 9 patients with HC but only two were found positive (BKPV load >1x108 copies/ml in both patients). Patients were treated with antiviral agents, mostly val/gancyclovir and foscarnet and cidofovir was added in persisting cases. In 12 patients with HC, >2 consecutive samples were available after the first documentation of BK (median 5, 3-7). In these patients a slow reduction of BK load was observed (median reduction: 0.9 log in 30 days) and all the patients maintained a high BKPV load (>1x105in 9/12) regardless of the resolution of cystitis.

Conclusion
In our study BKPV was related with the development of hemorrhagic cystitis after allo-HCT, with viral loads higher than 5,1x104 copies/ml strongly predicting hematuria. Despite the fact that CMV was also detected, CMV viruria or viremia were not found to be significant co-factors. Prospective studies are warranted to answer the benefit of viral molecular monitoring in urine among transplanted patients. 

Session topic: E-poster

Keyword(s): Allogeneic hematopoietic stem cell transplant, Hemorrhagic cystitis
Abstract: PB2165

Type: Publication Only

Background
Hemorrhagic cystitis (HC) after allogeneic hematopoetic cell transplantation (allo-HCT) has been recognized to be a relatively common severe complication with increased morbidity requiring hospitalization. Apart from conditioning toxicity, the most common pathogens implicated are cytomegalovirus (CMV) and BK-polyoma virus (BKPV). Data concerning the clinical relevance of molecular monitoring of these viruses in urine are scarce. 

Aims
We conducted a retrospective study enrolling patients who developed cystitis after allo-HCT to evaluate the urine viral load of both CMV and BKV that is potentially associated with HC . 

Methods
CMV and BKPV viral load in urine and CMV in plasma were measured with RQ-PCR in symptomatic patients with cystitis. Macroscopic hematuria (+/-clots) led to the diagnosis of hemorrhagic cystitis. 

Results
Twenty-nine patients (female=14, male=15), aged 16-61 years (median 35) who developed cystitis after allo-HCT and for who viral load data were available for both pathogens were included in the study. Patients suffered from hematological malignancies and underwent allo-HCT following myeloablative (21) or reduced intensity conditioning regimen (8). The majority of patients (17/29) received graft from a matched volunteer, 8/29 from siblings and 4 from a haplo-identical relative donor. Median time for the onset of cystitis was 48 days (7-677). Fourteen out of 29 (48%) patients experienced HC requiring hospitalization. CMV viral load in urine was positive in 7/29 samples (median: 1270 copies/ml, range: 180-1490000). Concordant CMV viremia was documented in 15 patients (median: 2570 copies/ml, range: 26-81000). BKPV viral load in urine was positive in 23/29 patients (median 2,5x107 copies/ml, range: 1,18x102-3,2x1010). Bacterial infection by klebsiella pneumonia was documented in one patient. Hemorrhagic cystitis was significantly associated with BKPV viral load: 2,5x107 in HC patients vs 1,9x104 in non-HC, p=0.018. A cut- off of 5,1x104 copies/ml could strongly predict the development of hematuria in ROC analysis. CMV viral load in urine and plasma tended to be higher in HC patients without a significant difference: (i) in urine: 106575 vs 523 copies/ml and (ii) in plasma: 9004 vs 2584 copies/ml for HC vs non-HC patients respectively, p=ns. No other clinical or biological factors could predict the development of HC. Cytology was available in 9 patients with HC but only two were found positive (BKPV load >1x108 copies/ml in both patients). Patients were treated with antiviral agents, mostly val/gancyclovir and foscarnet and cidofovir was added in persisting cases. In 12 patients with HC, >2 consecutive samples were available after the first documentation of BK (median 5, 3-7). In these patients a slow reduction of BK load was observed (median reduction: 0.9 log in 30 days) and all the patients maintained a high BKPV load (>1x105in 9/12) regardless of the resolution of cystitis.

Conclusion
In our study BKPV was related with the development of hemorrhagic cystitis after allo-HCT, with viral loads higher than 5,1x104 copies/ml strongly predicting hematuria. Despite the fact that CMV was also detected, CMV viruria or viremia were not found to be significant co-factors. Prospective studies are warranted to answer the benefit of viral molecular monitoring in urine among transplanted patients. 

Session topic: E-poster

Keyword(s): Allogeneic hematopoietic stem cell transplant, Hemorrhagic cystitis

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