Conditioning associated effects on oral mucosa and salivary function in allogeneic stem cell recipients

Abstract

Allogeneic hematopoietic stem cell transplantation (HSCT) is an effective treatment for patients with a range of disorders of the immunohematopoietic system. In HSCT recipients, acute complications in the oral cavity are common. They are related to the disease itself, its treatment, the pre-transplant status of the oral cavity, and nutritional problems during the neutropenic phase. As the results of treatment improve and survival rates increase, not only cure of the disease but also a variety of delayed side effects become apparent that make the compromised patient require special oral care. In order to improve the patient’s quality of life, this problem must be solved. The aim of this thesis was to investigate conditioning related effects on salivary function and on the oral mucosa, and also the impact of other risk factors for salivary dysfunction and oral mucositis in allogeneic HSCT recipients.

In patients conditioned with fractionated total body irradiation (fTBI) or single-dose total body irradiation (sTBI), we found that fTBI resulted in less reduction of salivary secretion rate one year after HSCT than sTBI, despite the higher total dose of radiation. In addition, we found that risk factors for a low stimulated salivary secretion rate (SSSR) one year after HSCT were sTBI and seropositivity of recipients for 3–4 herpes viruses. A cumulative increase in risk factors resulted in less salivary output. We found no difference in long-term salivary function after HSCT in 15-year olds who received conditioning with sTBI, fTBI, or busulfan (Bu). There was a negative correlation between age at conditioning with sTBI and salivary function. This correlation was not seen using fTBI or Bu. We also found a negative correlation between total systemic exposure to Bu and the SSSR. Female sex was a risk factor for salivary dysfunction at 15 years of age after HSCT.

Comparing myeloablative conditioning (MAC) to reduced intensity conditioning (RIC), we found that MAC was associated with a higher prevalence of oral mucositis (OM). Severe OM prolonged hospitalization. The introduction of a new intensive oral hygiene protocol was associated with lower OM score and the two scoring systems used for grading of OM showed good correlation.We also identified several risk factors for OM. In multivariate analysis, all donor-recipient gender combinations except the female-donor-male-recipient situation and year of transplantation—especially before the year 2011 when oral care was intensified—was significantly associated with a higher OM score.

In HSCT recipients, we found no difference in volume of gingival crevicular fluid (GCF) before, during, or after HSCT. When monitoring pro-inflammatory cytokines, we observed that cytokines are activated in the GCF. Patients conditioned with MAC or RIC had different patterns of pro-inflammatory cytokines, both in GCF and serum. There was a correlation between oral mucositis and an increase in IL-6 in the serum. Finally, we found no correlations between GCF and serum levels of cytokines at any time point.

In conclusion, both acute and long-term oral side effects are common after allogeneic HSCT. There is a lack of comprehensive and effective oral management regimens. By developing evidence-based recommendations that might improve the appropriateness of clinical practice, the acute oral complications might be reduced, patient outcomes would be better, and cost-effectiveness and quality of life would improve. Our findings also suggest that it is necessary to have long-term follow-up after allogeneic stem cell transplantation because some children will have permanently reduced salivary function. These people may require additional preventive measures throughout their lives in order to maintain proper oral health.