Abstract
We undertook a retrospective analysis of a cohort of 67 patients with multiple myeloma who had received an autologous haematopoietic SCT (HSCT) following high-dose melphalan to explore the impact of mucositis on the systemic inflammatory response. A homogenous group of 16 patients without a documented infection and a group of 30 patients with bacteraemia were identified for whom complete data on neutropenia, an inflammatory response, infectious complications and mucositis were available. All patients showed a similar course of events with an inflammatory response coinciding with the occurrence of significant mucositis, regardless of the presence or absence of infection. The only differences between the two groups were significantly higher maximum C-reactive protein (CRP) levels and lower citrulline levels for patients with bacteraemia, suggesting a causative role for mucositis in the occurrence of bacteraemia. Statistical analysis showed a significant association over time between citrulline levels, to a lesser extent bacteraemia, but not neutropenia, and the inflammatory response measured by CRP. These data suggest that the inflammatory response after conditioning for a HSCT is the result of the chemotherapy-induced mucositis and independent of neutropenia. Though primary inflammation appeared due to mucositis, infections resulting from mucosal barrier injury and neutropenia aggravated the inflammatory response.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Bodey GP, Buckley M, Sathe YS, Freireich EJ . Quantitative relationships between circulating leukocytes and infection in patients with acute leukemia. Ann Intern Med 1966; 64: 328–340.
de Pauw BE, Deresinski SC, Feld R, Lane-Allman EF, Donnelly JP . Ceftazidime compared with piperacillin and tobramycin for the empiric treatment of fever in neutropenic patients with cancer. A multicenter randomized trial. The Intercontinental Antimicrobial Study Group. Ann Intern Med 1994; 120: 834–844.
Furno P, Bucaneve G, Del FA . Monotherapy or aminoglycoside-containing combinations for empirical antibiotic treatment of febrile neutropenic patients: a meta-analysis. Lancet Infect Dis 2002; 2: 231–242.
Dekker A, Bulley S, Beyene J, Dupuis LL, Doyle JJ, Sung L . Meta-analysis of randomized controlled trials of prophylactic granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor after autologous and allogeneic stem cell transplantation. J Clin Oncol 2006; 24: 5207–5215.
Berghmans T, Paesmans M, Lafitte JJ, Mascaux C, Meert AP, Jacquy C et al. Therapeutic use of granulocyte and granulocyte-macrophage colony-stimulating factors in febrile neutropenic cancer patients. A systematic review of the literature with meta-analysis. Support Care Cancer 2002; 10: 181–188.
From the Immunocompromised Host Society. The design, analysis, and reporting of clinical trials on the empirical antibiotic management of the neutropenic patient. Report of a consensus panel. J Infect Dis 1990; 161: 397–401.
Sonis ST, Elting LS, Keefe D, Peterson DE, Schubert M, Hauer-Jensen M et al. Perspectives on cancer therapy-induced mucosal injury: pathogenesis, measurement, epidemiology, and consequences for patients. Cancer 2004; 100 (9 Suppl): 1995–2025.
Blijlevens NM . Implications of treatment-induced mucosal barrier injury. Curr Opin Oncol 2005; 17: 605–610.
Blijlevens NM, Donnelly JP, de Pauw BE . Mucosal barrier injury: biology, pathology, clinical counterparts and consequences of intensive treatment for haematological malignancy: an overview. Bone Marrow Transplant 2000; 25: 1269–1278.
Marron A, Carratala J, Gonzalez-Barca E, Fernandez-Sevilla A, Alcaide F, Gudiol F . Serious complications of bacteremia caused by Viridans streptococci in neutropenic patients with cancer. Clin Infect Dis 2000; 31: 1126–1130.
Costa SF, Miceli MH, Anaissie EJ . Mucosa or skin as source of coagulase-negative staphylococcal bacteraemia? Lancet Infect Dis 2004; 4: 278–286.
Ruescher TJ, Sodeifi A, Scrivani SJ, Kaban LB, Sonis ST . The impact of mucositis on alpha-hemolytic streptococcal infection in patients undergoing autologous bone marrow transplantation for hematologic malignancies. Cancer 1998; 82: 2275–2281.
Blijlevens NM, Donnelly JP, de Pauw BE . Impaired gut function as risk factor for invasive candidiasis in neutropenic patients. Br J Haematol 2002; 117: 259–264.
Elting LS, Shih YC . The economic burden of supportive care of cancer patients. Support Care Cancer 2004; 12: 219–226.
MacGregor RR, Beaty HN . Evaluation of positive blood cultures. Guidelines for early differentiation of contaminated from valid positive cultures. Arch Intern Med 1972; 130: 84–87.
Potting CM, Blijlevens NA, Donnelly JP, Feuth T, van Achterberg T . A scoring system for the assessment of oral mucositis in daily nursing practice. Eur J Cancer Care (Engl) 2006; 15: 228–234.
Blijlevens NM, Lutgens LC, Schattenberg AV, Donnelly JP . Citrulline: a potentially simple quantitative marker of intestinal epithelial damage following myeloablative therapy. Bone Marrow Transplant 2004; 34: 193–196.
Crenn P, Vahedi K, Lavergne-Slove A, Cynober L, Matuchansky C, Messing B . Plasma citrulline: a marker of enterocyte mass in villous atrophy-associated small bowel disease. Gastroenterology 2003; 124: 1210–1219.
Blijlevens NM, Donnelly JP, DePauw BE . Inflammatory response to mucosal barrier injury after myeloablative therapy in allogeneic stem cell transplant recipients. Bone Marrow Transplant 2005; 36: 703–707.
Tsuji E, Hiki N, Nomura S, Fukushima R, Kojima J, Ogawa T et al. Simultaneous onset of acute inflammatory response, sepsis-like symptoms and intestinal mucosal injury after cancer chemotherapy. Int J Cancer 2003; 107: 303–308.
Mullighan CG, Bardy PG . New directions in the genomics of allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2007; 13: 127–144.
Slavin MA, Grigg AP, Schwarer AP, Szer J, Spencer A, Sainani A et al. A randomized comparison of empiric or pre-emptive antibiotic therapy after hematopoietic stem cell transplantation. Bone Marrow Transplant 2007; 40: 157–163.
Offidani M, Corvatta L, Olivieri A, Rupoli S, Frayfer J, Mele A et al. Infectious complications after autologous peripheral blood progenitor cell transplantation followed by G-CSF. Bone Marrow Transplant 1999; 24: 1079–1087.
Spielberger R, Stiff P, Bensinger W, Gentile T, Weisdorf D, Kewalramani T et al. Palifermin for oral mucositis after intensive therapy for hematologic cancers. N Engl J Med 2004; 351: 2590–2598.
Parker JE, Shafi T, Pagliuca A, Mijovic A, Devereux S, Potter M et al. Allogeneic stem cell transplantation in the myelodysplastic syndromes: interim results of outcome following reduced-intensity conditioning compared with standard preparative regimens. Br J Haematol 2002; 119: 144–154.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
van der Velden, W., Blijlevens, N., Feuth, T. et al. Febrile mucositis in haematopoietic SCT recipients. Bone Marrow Transplant 43, 55–60 (2009). https://doi.org/10.1038/bmt.2008.270
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/bmt.2008.270