Association of HSV reactivation and pro-inflammatory cytokine levels with the severity of stomatitis after BEAM chemotherapy and autologous SCT

Springer Science and Business Media LLC - Tập 19 - Trang 1211-1216 - 2010
Maria J. G. T. Rüping1, Constance Keulertz2, Jörg J. Vehreschild1, Harry Lövenich3, Dietmar Söhngen4, Ulrike Wieland5, Oliver A. Cornely1,6,7
1Uniklinik Köln, Klinik I für Innere Medizin, Köln, Germany
2Uniklinik Köln, Klinik I für Anästhesiologie und Operative Intensivmedizin, Köln, Germany
3St. Jans Gasthuis, Neurologie, Weert, the Netherlands
4Reha-Zentrum Reichshof, Reichshof-Eckenhagen, Germany
5Uniklinik Köln, Institut für Virologie, Köln, Germany
6Uniklinik Köln, Zentrum für Klinische Studien (ZKS) (BMBF 01KN0706), Köln, Germany
7Uniklinik Köln, Köln, Germany

Tóm tắt

Stomatitis, including oral mucositis and ulcerations induced by HSV-reactivation are major sources of morbidity after high-dose (HD) chemotherapy and subsequent autologous hematopoietic stem cell transplantation (SCT). While increased synthesis of pro-inflammatory cytokines, such as interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF-α)—as well as reactivation of viral infections have frequently been observed in this setting, data on their association with the severity of mucositis is limited. Fifteen patients with Hodgkin's or non–Hodgkin's lymphoma receiving HD conditioning chemotherapy and autologous SCT were assessed with respect to oral pain and severity of stomatitis on day –6, 0, +5 to +7, +13 to +15, and +100. On the same dates, IL-1 and TNF-α were quantified in saliva and screening for a wide range of viral pathogens was carried out by cell culture and PCR and complemented by serological analyses. t Tests were used to assess potential associations between these variables. All but one patient had a positive HSV IgG titer at baseline. Reactivation as confirmed by HSV PCR was observed in seven patients (50%). There was a significant association between the presence of HSV in saliva samples and severity of stomatitis (t test, p = 0.015). The highest concentration of TNF-α and IL-1 coincided with the maximum intensity of stomatitis, but the association was not significant. We found a significant association between the presence of HSV in saliva samples and severity of stomatitis in patients receiving HD chemotherapy and subsequent autologous SCT. While acyclovir prophylaxis has become standard for patients undergoing allogeneic SCT, this issue has not been sufficiently explored for other chemotherapy regimens. Based on our findings, conduction of a well-powered controlled randomized trial may be warranted.

Tài liệu tham khảo

National Cancer Institute (2010) Oral Complications of Chemotherapy and Head/Neck Radiation. National Cancer Institute, Bethesda, MD, USA

Alvarado Y, Bellm LA, Giles FJ (2002) Oral mucositis: time for more studies. Hematology 7:281–289

Attal M, Huguet F, Rubie H, Charlet JP, Schlaifer D, Huynh A, Laurent G, Pris J (1993) Prevention of regimen-related toxicities after bone marrow transplantation by pentoxifylline: a prospective, randomized trial. Blood 82:732–736

Bianco JA, Appelbaum FR, Nemunaitis J, Almgren J, Andrews F, Kettner P, Shields A, Singer JW (1991) Phase I-II trial of pentoxifylline for the prevention of transplant-related toxicities following bone marrow transplantation. Blood 78:1205–1211

Blijlevens N, Schwenkglenks M, Bacon P, D'Addio A, Einsele H, Maertens J, Niederwieser D, Rabitsch W, Roosaar A, Ruutu T, Schouten H, Stone R, Vokurka S, Quinn B, McCann S (2008) Prospective oral mucositis audit: oral mucositis in patients receiving high-dose melphalan or BEAM conditioning chemotherapy--European Blood and Marrow Transplantation Mucositis Advisory Group. J Clin Oncol 26:1519–1525

Doi Y, Ninomiya T, Hata J, Yonemoto K, Tanizaki Y, Arima H, Liu Y, Rahman M, Iida M, Kiyohara Y (2009) Seroprevalence of herpes simplex virus 1 and 2 in a population-based cohort in Japan. J Epidemiol 19:56–62

Donnelly JP, Bellm LA, Epstein JB, Sonis ST, Symonds RP (2003) Antimicrobial therapy to prevent or treat oral mucositis. Lancet Infect Dis 3:405–412

Eigler A, Loher F, Endres S (2001) 34. Internist (Berl) 42:28–34

Eilers J, Berger AM, Petersen MC (1988) Development, testing, and application of the oral assessment guide. Oncol Nurs Forum 15:325–330

Eisen D, Essell J, Broun ER, Sigmund D, DeVoe M (2003) Clinical utility of oral valacyclovir compared with oral acyclovir for the prevention of herpes simplex virus mucositis following autologous bone marrow transplantation or stem cell rescue therapy. Bone Marrow Transplant 31:51–55

Fall-Dickson JM, Ramsay ES, Castro K, Woltz P, Sportes C (2007) Oral mucositis-related oropharyngeal pain and correlative tumor necrosis factor-alpha expression in adult oncology patients undergoing hematopoietic stem cell transplantation. Clin Ther 29(Suppl):2547–2561

Gluckman E, Lotsberg J, Devergie A, Zhao XM, Melo R, Gomez-Morales M, Mazeron MC, Perol Y (1983) Oral acyclovir prophylactic treatment of herpes simplex infection after bone marrow transplantation. J Antimicrob Chemother 12(Suppl B):161–167

Hann IM, Prentice HG, Blacklock HA, Ross MG, Brigden D, Rosling AE, Burke C, Crawford DH, Brumfitt W, Hoffbrand AV (1983) Acyclovir prophylaxis against herpes virus infections in severely immunocompromised patients: randomised double blind trial. Br Med J (Clin Res Ed) 287:384–388

Jacobs MV, Snijders PJ, van den Brule AJ, Helmerhorst TJ, Meijer CJ, Walboomers JM (1997) A general primer GP5+/GP6(+)-mediated PCR-enzyme immunoassay method for rapid detection of 14 high-risk and 6 low-risk human papillomavirus genotypes in cervical scrapings. J Clin Microbiol 35:791–795

Kramer MA, Uitenbroek DG, Ujcic-Voortman JK, Pfrommer C, Spaargaren J, Coutinho RA, Dukers-Muijrers NH (2008) Ethnic differences in HSV1 and HSV2 seroprevalence in Amsterdam, the Netherlands Euro Surveill 13

Liedtke W, Opalka B, Zimmermann CW, Lignitz E (1993) Age distribution of latent herpes simplex virus 1 and varicella-zoster virus genome in human nervous tissue. J Neurol Sci 116:6–11

Liesveld JL, Abboud CN, Ifthikharuddin JJ, Lancet JE, Wedow LA, Oliva J, Stamm CG, Nichols D (2002) Oral valacyclovir versus intravenous acyclovir in preventing herpes simplex virus infections in autologous stem cell transplant recipients. Biol Blood Marrow Transplant 8:662–665

Logan RM, Stringer AM, Bowen JM, Yeoh AS, Gibson RJ, Sonis ST, Keefe DM (2007) The role of pro-inflammatory cytokines in cancer treatment-induced alimentary tract mucositis: pathobiology, animal models and cytotoxic drugs. Cancer Treat Rev 33:448–460

Malvy D, Halioua B, Lancon F, Rezvani A, Bertrais S, Chanzy B, Daniloski M, Ezzedine K, Malkin JE, Morand P, De Labareyre C, Hercberg S, El Hasnaoui A (2005) Epidemiology of genital herpes simplex virus infections in a community-based sample in France: results of the HERPIMAX study. Sex Transm Dis 32:499–505

Morfin F, Bilger K, Boucher A, Thiebaut A, Najioullah F, Bleyzac N, Raus N, Bosshard S, Aymard M, Michallet M, Thouvenot D (2004) HSV excretion after bone marrow transplantation: a 4-year survey. J Clin Virol 30:341–345

Mulder PO, Schroder P, de Vries-Hospers HG, van der Geest S, Sleijfer DT, Mulder NH, de Vries EG (1989) Incidence and effects of herpes simplex virus infection after autologous bone marrow transplantation for solid tumours. Neth J Med 34:126–131

Pohl-Koppe A, Dahm C, Elgas M, Kuhn JE, Braun RW, ter Meulen V (1992) The diagnostic significance of the polymerase chain reaction and isoelectric focusing in herpes simplex virus encephalitis. J Med Virol 36:147–154

Saral R, Ambinder RF, Burns WH, Angelopulos CM, Griffin DE, Burke PJ, Lietman PS (1983) Acyclovir prophylaxis against herpes simplex virus infection in patients with leukemia. A randomized, double-blind, placebo-controlled study. Ann Intern Med 99:773–776

Saral R, Burns WH, Laskin OL, Santos GW, Lietman PS (1981) Acyclovir prophylaxis of herpes-simplex-virus infections. N Engl J Med 305:63–67

Sonis ST (2004) Pathobiology of mucositis. Semin Oncol Nurs 20:11–15

Sonis ST, Elting LS, Keefe D, Peterson DE, Schubert M, Hauer-Jensen M, Bekele BN, Raber-Durlacher J, Donnelly JP, Rubenstein EB (2004) Perspectives on cancer therapy-induced mucosal injury: pathogenesis, measurement, epidemiology, and consequences for patients. Cancer 100:1995–2025

Stockschlader M, Kalhs P, Peters S, Zeller W, Kruger W, Kabisch H, Lechner K, Zander A (1993) Intravenous pentoxifylline failed to prevent transplant-related toxicities in allogeneic bone marrow transplant recipients. Bone Marrow Transplant 12:357–362

van der Jagt RH, Pari G, McDiarmid SA, Boisvert DM, Huebsch LB (1994) Effect of pentoxifylline on regimen related toxicity in patients undergoing allogeneic or autologous bone marrow transplantation. Bone Marrow Transplant 13:203–207

Wade JC, Newton B, Flournoy N, Meyers JD (1984) Oral acyclovir for prevention of herpes simplex virus reactivation after marrow transplantation. Ann Intern Med 100:823–828

Warkentin DI, Epstein JB, Campbell LM, Yip JG, Cox VC, Ransier A, Barnett MJ, Marra F (2002) Valacyclovir versus acyclovir for HSV prophylaxisin neutropenic patients. Ann Pharmacother 36:1525–1531

Thông tin
Thông tin xuất bản

Springer Science and Business Media LLC

Tập 19

1211-1216

Thông tin tác giả