Oral health of patients with severe haematological malignancies and disorders before and after haematopoietic stem cell transplantation

ABSTRACT
Introduction and objectives: Potentially lethal haematological disorders and malignancies – such as myelodysplastic syndromes, acute and chronic leukaemias, severe aplastic anaemias and lymphomas – represent a heterogeneous group of diseases characterised by alterations in the proliferation and function of blood cells. It was reported decades ago that patients with acute leukaemia (AL) have signs of specific leukaemia-related oral lesions, such as petechias, gingival bleeding, and gingival swelling. Previous studies have also concluded that general dental treatment needs to be high among haematological cancer patients at the time of diagnosis and before cancer treatments, but the data are sparse. Thus, there is a need to gather contemporary information on the state of oral health of these patients.
Poor oral health is considered a risk factor for several diseases, including specific cancers, but the associations between oral health and severe haematological malignancies and disorders are unclear. The existing knowledge is based on a limited number of studies and the results are contradictory.
Treatments of these disorders and malignancies are often intensive and may include chemotherapy, radiation therapy, and haematopoietic stem cell transplantation (HSCT). Thus, the elimination of possible oral foci has been suggested in oral health protocols for such patients. As well as the disorders and malignancies themselves, their treatments are known to affect oral health. As HSCT procedures and success rates have increased, a growing number of patients have experienced serious short- and long-term side effects and comorbidities. Due to the toxic effects of chemotherapies, total body irradiation, and immunosuppression, HSCT recipients are at risk of oral side effects during and after HSCT. Side effects of the therapy in the oral cavity are common and approximately 80% of patients are affected by comorbidities such as mucositis, hyposalivation, and graft versus host disease (GvHD).
The purpose of this thesis was to investigate the oral health parameters of adult patients with severe haematological malignancy or disorder before HSCT and the progression of the oral health parameters post-HSCT. The results were compared with controls of normal population. Additionally, the associations between oral health parameters and hyposalivation with survival were investigated.
Methods: A group of 572 adult patients referred for dental examination to University Center for Dental Medicine Basel from Hematological Department of University Hospital Basel between 2008 and 2018 was included in the sub-studies of this thesis. From 2008 to 2016, the data collection was retrospective, and for 2018 prospective. A dental examination conducted included the following: decayed, missing, and filled teeth (DMFT) index; calculation of number of teeth; stimulated salivary flow rate (SSFR); presence of periodontitis; presence of acute infections; panoramic radiographs and if needed, additional radiographs. After HSCT, the presence of oral GvHD was additionally examined. In the longitudinal part of the study, the patients were examined six, 12, and 24 months post-HSCT. The changes in SSFR and influence of SSFR on other oral health parameters and on six-month survival were examined.
The control group consisted of 289 adults recruited from the Swiss Bone Marrow Donor Registry of the Blood Transfusion Service SRC Basel, Switzerland. Oral examination was performed for the controls in University Center for Dental Medicine Basel, in a process similar to that previously described – with the exception that radiographs were not taken and, instead, a clinical periodontal status was performed.
In the first sub-study (8.1), the final study population included 143 allogeneic HSCT recipients matched with controls by age and sex. In the second sub-study (8.2), a total of 149 patients who had got their haematological diagnosis not more than six months ago were included and compared with a control group of 154 subjects of same mean age. For the longitudinal part of the study (8.3), 269 allogeneic HSCT recipients were included.
Results: In the first sub-study (8.1), the mean SSFR and mean DMFT index and number of caries lesions were observed to be poorer among HSCT recipients than controls (all p-values < 0.05). Acute symptomatic infections were observed in nine HSCT recipients (6.3%) and none of the controls. The number of teeth was lower among the HSCT recipients, but no statistically significant difference was observed. Statistically significant differences in the measures of current or previous periodontitis were not observed.
In the second sub-study (8.2), where patients with newly diagnosed severe haematological malignancy or disorder were compared with controls, the mean SSFR of the patients was significantly lower than the mean SSFR of the controls (p < 0.005). Additionally, the number of caries lesions was significantly higher in the patient group than in the control group (p < 0.005). There were fewer teeth and a higher DMFT index in the patient group compared to the control group, but the differences were not statistically significant. Acute symptomatic infections were observed in eight (5.4%) patients and in none of the controls (p < 0.01).
In the third longitudinal study (8.3), 40 HSCT recipients (14.8%) died within six months after HSCT. Among the deceased recipients, hyposalivation and caries were more common pre-HSCT than in recipients who survived more than six months (p < 0.05). HSCT recipients with hyposalivation pre-HSCT had a higher risk of death (HR: 1.90, 95% CI: 1.00-3.60; p = 0.044) within six months post-HSCT compared to recipients without hyposalivation. Additionally, hyposalivation pre-HSCT was associated with a higher DMFT index score (p < 0.05) and a lower number of teeth (p < 0.005) 24 months post-HSCT in comparison to those without hyposalivation.
Conclusions and clinical relevance: Patients with severe haematological disease demonstrated a high prevalence of oral disorders at the time of diagnosis and at the time of pre-HSCT. Hyposalivation and caries were associated with a lower rate of survival in HSCT recipients. In addition, hyposalivation predisposed patients to deterioration of oral health post-HSCT. These findings support the recommendations for early dental examination at the time of diagnosis. Efficient preventive strategies are important to maintain the oral health of these patients.