Abstract
ObjectiveThis prospective study evaluated clinical risk indicators as well as pro- and anti- inflammatory mediators at the time of malignancy diagnosis in relation to chemotherapy-related oral mucositis in pediatric population.MethodsPatients (n = 104) under 18 years of age with primary malignancies and undergoing chemotherapy were included. Potential risk indicators were analyzed using binary logistic regression with oral mucositis as the outcome. In a subgroup (n = 35), plasma samples at the time of malignancy diagnosis were analyzed for inflammatory cytokines and an antimicrobial protein pro-LL-37 (hCAP18).ResultsIn the multivariable model, type of malignancy diagnosis was significantly associated with oral mucositis, with highest risk of oral mucositis in patients with acute leukemia compared to those with lymphoma or solid tumors. At the time of malignancy diagnosis, plasma from patients with acute leukemia displayed higher concentrations (P<0.05) of IL-6, IL-8, IL-10, and TNF-α and lower levels of pro-LL-37 (P<0.001).ConclusionsThe results imply that pretherapeutic high levels of inflammatory cytokines and low levels of pro-LL-37 in plasma might contribute to the high incidence of oral mucositis in patients with acute leukemia. These findings may add to our understanding of the predispositions to oral mucositis in children with malignancies.
Highlights
Mucositis, which can involve the entire alimentary tract, is a major complication of cytostatic chemotherapy
We previously showed that the antimicrobial protein pro-LL-37, synthesized by myeloid cells in the bone marrow, is severely reduced in patients with severe congenital neutropenia, a condition of defective myelopoiesis [17]
The time from the start of the entire chemotherapy protocol to the occurrence of oral mucositis ranged from three days to 28 weeks, with a median value of six weeks in patients with acute leukemia, one week in lymphoma, and three weeks in solid tumors (Figure 1)
Summary
Mucositis, which can involve the entire alimentary tract, is a major complication of cytostatic chemotherapy. Oral mucositis occurs in the mucosal lining of the oral cavity and mainly affects the non-keratinized epithelium. It may cause severe pain and bleeding, increase the risk of systemic infection, and further complicate anticancer treatment [1,2]. Within studies on pediatric patients, parameters including body weight prior to chemotherapy [4], blood type [5], underlying malignant disease [6], specific chemotherapy regimens or protocols [7,8], serum creatinine level [4], blood methotrexate concentration [9], and neutropenia [4,10,11] have been suggested as risk factors for developing oral mucositis. The relative contribution of these risk factors in relation to mucositis is not clear, which makes it difficult to identify the patients at a higher risk of oral mucositis
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