title: Association of HSV reactivation and pro-inflammatory cytokine levels with the severity of stomatitis after BEAM chemotherapy and autologous SCT.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Uniklinik Köln, Klinik I für Innere Medizin, Köln, Germany.
authors.forename: Maria J G T
authors.initials: MJ
authors.lastname: Rüping
authors.forename: Constance
authors.initials: C
authors.lastname: Keulertz
authors.forename: Jörg J
authors.initials: JJ
authors.lastname: Vehreschild
authors.forename: Harry
authors.initials: H
authors.lastname: Lövenich
authors.forename: Dietmar
authors.initials: D
authors.lastname: Söhngen
authors.forename: Ulrike
authors.initials: U
authors.lastname: Wieland
authors.forename: Oliver A
authors.initials: OA
authors.lastname: Cornely
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D002330:Carmustine / Q000009:adverse effects; D003561:Cytarabine / Q000009:adverse effects; D016207:Cytokines / Q000097:blood*; D005260:Female; D018259:Herpesvirus 1, Human; D018258:Herpesvirus 2, Human; D006689:Hodgkin Disease; D006801:Humans; D007249:Inflammation / Q000097:blood; D007375:Interleukin-1 / Q000097:blood; D008228:Lymphoma, Non-Hodgkin; D008297:Male; D008558:Melphalan / Q000009:adverse effects; D008875:Middle Aged; D011034:Podophyllotoxin / Q000009:adverse effects; D012463:Saliva / Q000737:chemistry; D012720:Severity of Illness Index; D013223:Statistics as Topic; D033581:Stem Cell Transplantation / Q000009:adverse effects*; D013280:Stomatitis / Q000139:chemically induced* / Q000473:pathology; D014182:Transplantation, Autologous / Q000009:adverse effects; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D055815:Young Adult
chemical_list: D016207:Cytokines; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D003561:Cytarabine; D011034:Podophyllotoxin; D008558:Melphalan; D002330:Carmustine