###### Abstract  
Salivary gland dysfunction is an underestimated oral late effect of chemotherapy in childhood cancer survivors (CCS). Therefore, the aim of this cross-sectional study was to assess the salivary functioning and dental caries experience in Italian CSSs and age- and gender-matched healthy children. A total of 32 children (15 females and 17 males, age range 6-14 years) in remission from hematological malignancy and 32 healthy controls were compared for salivary parameters (stimulated whole salivary flow rate, pH, and buffer capacity) and presence of carious lesions in the primary and permanent dentition using the dmft/DMFT indexes. Significantly lower stimulated whole saliva (SWS) and pH were observed in CSS than in healthy pediatric patients (both \(p<0.001\)), together with a higher prevalence of carious lesions on both the deciduous (\(p=0.002\)) and permanent teeth (\(p=0.015\)). SWS was more severely impaired in children treated with chemotherapy before 5 years of age (\(p<0.001\)) and, in spite of the tendency to improve over time, low SWS was still observed after 5-9 years of disease remission. According to the present data, chemotherapy has a detrimental effect on salivary gland functioning, which would seem to maintain up to 9 years after antineoplastic treatment. childhood; chemotherapy; acute lymphoblastic leukemia; saliva; cancer survivors +
Footnote †: journal: Medical  
Chemotherapy (CT) is the primary therapeutic approach used in pediatric hematological tumors [7] and has adverse effects on oral health status [8; 9; 10; 11]. As such, high prevalence of oral dryness, mucosal ulceration, and dental decay has been reported in these children, mostly secondary to changes in saliva functioning and properties. Salivary glands and mucous membranes are highly vulnerable to the cytotoxic agents, due to their high turnover rate [8]. In particular, CT can impact the excretion flow rate of saliva, its organic and inorganic composition, as well as its immunological and antioxidant characteristics [12; 13]. Changes in free radicals and antioxidant levels may play an important role in the onset of oxidative stress-related oral pathologies [12]. Decreased salivary flow in pediatric cancer patients increases their risk of being affected by infectious odontogenic processes and gingival and mucosal inflammation, as whole saliva is a fundamental biofluid for maintaining oral homeostasis [9; 10; 11]. Its complex protective role is related to mechanical cleansing functions and lubrication of mucosal surfaces, buffering capacity, maintenance of tooth integrity, facilitation of cell healing, and antibacterial activity [14]. Alterations of such biochemical properties along with the impairment of oral hygiene status, accumulated over time, may manifest as increased caries activity [15]. Unfortunately, most studies assessed salivary gland functioning only during CT with no long-term follow-up. Derangements in the rheological characteristics of saliva have been described during the induction and consolidation phases of CT [13; 16; 17], and they have been positively correlated to the neutrophil counts in children suffering from ALL [16]. Conversely, other studies failed to demonstrate any adverse effect of CT on salivary glands in the early stage of cancer treatment [18; 19; 20]. Long-term data are scarce [21; 22], and most of them focused on hematopoietic stem cell transplantation (HSCT) recipients [23; 24]. Reduced salivary flow has been observed even 5 to 15 years after CT [21; 22]. Considering that salivary gland dysfunction is an underestimated oral late effect of CT in pediatric patients, it is important to understand more about the long-term alterations in the salivary parameters and their correlation with oral health status. Changes in quantitative and qualitative characteristics of whole saliva may hamper the oral environment equilibrium, predisposing to gingival inflammation and dental caries occurrence [12; 25].