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Bone Marrow Transplantation (2007) 39, 57& 2007 Nature Publishing Group All rights reserved 0268-3369/07 $30.00 Hyaluronate and risperidone for hemorrhagic cystitis Bone Marrow Transplantation (2007) 39, 57.
doi:10.1038/sj.bmt.1705546; published online 20 November2006 1 Miodosky M, Abdul-Hai A, Tsirigotis P, Or B, Bitan M, Resnick IB et al. Treatment of post-hematopoietic stem celltransplantation hemorrhagic cystitis with intravesicular so-dium hyaluronate. Bone Marrow Transplant 2006; 38: 507–511.
In the report by Miodosky et al.,1 five of seven patients with 2 Gorczynska E, Turkiewicz D, Rybka K, Toporski J, Kalwak post-hematopoietic transplantation hemorrhagic cystitis K, Dyla A et al. Incidence, clinical outcome, and management (HC) experienced complete response to intravesical sodium of virus-induced hemorrhagic cystitis in children and adoles- hyaluronate, although three patients required two instilla- cents afterallogeneic hematopoietic cell transplantation. Biol tions to achieve this. HC has been shown to be commonly Blood Marrow Transplant 2005; 11: 797–804.
associated with all the polyomaviruses.2,3 These polyoma- 3 Comar M, D’Agaro P, Andolina M, Maximova N, Martini F, viruses replicate in the urinary tract4 and upregulate Tognon M et al. Hemorrhagic cystitis in children undergoing expression of hyaluronan in renal tubule cells.5 We bone marrow transplantation: a putative role for simian virus40. Transplantation 2004; 78: 544–548.
hypothesize that sodium hyaluronate, apart from mechani- 4 Boldorini R, Veggiani C, Barco D, Monga G. Kidney and cally protecting the bladder from uroepithelial damage, urinary tract polyomavirus infection and distribution: mole- alters a vital step in the life cycle of polyomaviruses.
cularbiology investigation of 10 consecutive autopsies. Arch Furthermore, degradation products of hyaluronate created by urinary hyaluronidase could trigger the secretion of 5 Piedagnel R, Prie D, Cassingena R, Ronco PM, Lelongt B.
various cytokines and chemokines by macrophages,6 which SV40 large-T oncogene inhibits transcription of perlecan- related proteoglycans but stimulates hyaluronan synthesis in a A different approach for JC virus (JCV)-related hemor- temperature-sensitive renal-tubule principal cell line. J Biol rhagic cystitis involves 5-HT2a, the cell receptor required forJCV entry.7 We recently reported a dramatic clinical 6 Jobe K, Odman-Ghazi S, Whalen M, Vercruysse K. Inter- leukin-12 release from macrophages by hyaluronan, chondro- and virological response in a haploidentical, T-cell-depleted itin sulfate A and chondroitin sulfate C oligosaccharides.
hematopoietic stem cell transplant recipient with biopsy- proven progressive multifocal leukoencephalopathy (an- 7 Elphick GF, Querbes W, Jordan JA, Gee GV, Eash S, Manley K et al. The human polyomavirus, JCV, uses serotonin doses of the high-affinity 5-HT2a antagonist risperidone.8 receptors to infect cells. Science 2004; 306: 1380–1383.
Risperidone has been safely used in humans over the last 20 8 Focosi D, Fazzi R, Montanaro D, Emdin M, Petrini M. A years to treat psychiatric illness and is generally well comatose woman with severe progressive multifocal encepha- tolerated. We also showed a 2-log reduction in JC viruria lopathy who woke up and is JC virus free after treatment with after treatment of psychiatric patients with risperidone.9 risperidone. Antiviral Res 2006, in press.
On the basis of these findings, we encourage a clinical 9 Kast R. JC viruria eradication by risperidone in a woman with meningioma. Antiviral Res 2006, in press.
trial of risperidone in late-onset post-transplant HC, 10 Chang H, Wang M, Tsai RT, Lin HS, Huan JS, Wang WC particularly in non-responders to intravesical sodium et al. High incidence of JC viruria in JC-seropositive older hyaluronate. Given the high incidence of JC viruria in the individuals. J Neurovirol 2002; 8: 447–451.
general population,10 consideration of prophylactic risper-idone could be given if our suspicions about risperidone’santi-JCV properties prove correct.
1Division of Hematology, Azienda Ospedaliera Santa Chiara, University of Pisa, Pisa, Italy and 2Department of Psychiatry, University of Vermont, 3These authors contributed equally to this manuscript Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.

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