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

• Published in: Bone marrow transplantation (Basingstoke) Vol. 49; no. 5; pp. 664 - 670
• Main Authors: Gilis, L, Morisset, S, Billaud, G, Ducastelle-Leprêtre, S, Labussière-Wallet, H, Nicolini, F-E, Barraco, F, Detrait, M, Thomas, X, Tedone, N, Sobh, M, Chidiac, C, Ferry, T, Salles, G, Michallet, M, Ader, F
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.05.2014; Nature Publishing Group
• Subjects: 631/532/1542; 692/699/255/2514; 692/699/2768/1335; 692/700/565/545/576/1955; Adolescent; Adult; Aged; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Antiviral Agents - therapeutic use; Bacteriology; Biological and medical sciences; BK Virus; Blood; Bone marrow; Bone marrow, stem cells transplantation. Graft versus host reaction; Cell Biology; Cord blood; Cystitis; Cystitis - economics; Cystitis - epidemiology; Cystitis - virology; Cytosine - analogs & derivatives; Cytosine - therapeutic use; Economic analysis; Economic impact; Female; Graft vs Host Disease - economics; Graft vs Host Disease - epidemiology; Graft-versus-host reaction; Health Care Costs; Hematologic Neoplasms - economics; Hematologic Neoplasms - epidemiology; Hematologic Neoplasms - therapy; Hematology; Hematopoietic Stem Cell Transplantation - adverse effects; Hematopoietic Stem Cell Transplantation - economics; Hematopoietic stem cells; Hemorrhage; Hemorrhagic cystitis; Histocompatibility antigen HLA; Hospital Costs; Humans; Immunology; Impact analysis; Incidence; Infectious diseases; Internal Medicine; Life Sciences; Male; Medical sciences; Medicine; Medicine & Public Health; Microbiology and Parasitology; Middle Aged; Morbidity; Mortality; Multivariate analysis; Nephrology. Urinary tract diseases; Organophosphonates - therapeutic use; original-article; Peripheral blood; Polyomavirus Infections - drug therapy; Polyomavirus Infections - economics; Polyomavirus Infections - epidemiology; Public Health; Risk analysis; Risk Factors; Risk groups; Stem cell research; Stem cell transplantation; Stem Cells; Subgroups; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Transplantation; Transplantation, Homologous; Tumor Virus Infections - drug therapy; Tumor Virus Infections - economics; Tumor Virus Infections - epidemiology; Urinary system involvement in other diseases. Miscellaneous; Urinary tract. Prostate gland; Viral diseases; Viremia; Viremia - complications; Viremia - drug therapy; Viremia - immunology; Virology; Virus diseases; Viruses; Young Adult; cidofovir; BK virus; hemorrhagic cystitis; allogeneic hematopoietic SCT; PCR; Stem cell; Hematopoietic cell; Homograft; Nucleotide analog; Papovaviridae; Allogeneic hematopoietic stem cell transplantation; Nucleoside analog; Graft; Antiviral; DNA polymerase inhibitor; Human; Acyclic nucleotide; Urinary system disease; Hematology; Polyomavirus; Organic phosphonate; Cidofovir; Urinary tract disease; Infection; Virus; Polymerase chain reaction; Associated virus; Viral disease; Bladder disease; Molecular biology; Pyrimidine nucleotide; Hemorrhagic cystitis; Hospital Costs; Tumor Virus Infections; Hematologic Neoplasms; Viremia; Humans; Middle Aged; Male; Transplantation; Homologous; BK Virus; Graft vs Host Disease; Incidence; Young Adult; Adult; Female; Cytosine; Cystitis; Risk Factors; Hematopoietic Stem Cell Transplantation; Antiviral Agents; Organophosphonates; Polyomavirus Infections; Health Care Costs; Adolescent; Aged
• ISSN: 0268-3369; 1476-5365
• DOI: 10.1038/bmt.2013.235

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 =0.028), unrelated donor ( P =0.0178), stem cell source ( P =0.0001), HLA mismatching ( P =0.0022) and BU in conditioning regimen ( P =0.01) were associated with a higher risk of developing BKV-HC. In multivariate analysis, patients receiving cord blood units (CBUs) ( P =0.0005) and peripheral blood stem cells ( P =0.011) represented high-risk subgroups for developing BKV-HC. BK viremia was directly correlated to HC severity ( P =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 ( P <0.0001), more RBC ( P =0.0003) and platelet transfusions ( P <0.0001). Over the 5-year study period, the financial cost of the complication was evaluated at €2 376 076 ($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.