Subjective Oral Dryness following Hematopoietic Cell Transplantation: A Report from the Orastem Study.

Xerostomia, or subjective oral dryness, is a serious complaint after hematopoietic cell transplantation (HCT). Xerostomia is rated as one of the most bothersome symptoms by HCT recipients, negatively affecting quality of life. This substudy of the Orastem study, a prospective longitudinal, international, observational, multicenter study, aimed to describe the prevalence and severity of xerostomia following HCT. Furthermore, the effect of the conditioning regimen, type of transplantation, and oral mucosal changes related to chronic graft-versus-host disease (cGVHD) in the development of xerostomia were studied. All HCT recipients rated xerostomia on a scale of 0 to 10 before the conditioning regimen, several times early post-HCT, and at 3 months post-HCT, and only allogeneic HCT recipients also rated xerostomia at 6 and 12 months post-HCT. In addition, stimulated whole mouth saliva was collected several times. Linear regression models and longitudinal mixed-effects models were created to investigate the influence of risk indicators on xerostomia. A total of 99 autologous and 163 allogeneic HCT recipients were included from 6 study sites in Sweden, Canada, the Netherlands, and the United States. The prevalence of xerostomia was 40% before the conditioning regimen, 87% early post-HCT, and 64% at 3 months post-HCT. Complaints after autologous HCT were transient in nature, while the severity of xerostomia in allogeneic HCT recipients remained elevated at 12 months post-HCT. Compared to autologous HCT recipients, allogeneic HCT recipients experienced 1.0 point more xerostomia (95% confidence interval [CI], .1 to 2.0) early post-HCT and 1.7 points more (95% CI, .4 to 3.0) at 3 months post-HCT. Allogeneic HCT recipients receiving a high-intensity conditioning regimen experienced more xerostomia compared to those receiving a nonmyeloablative or reduced-intensity conditioning regimen. The difference was 2.0 points (95% CI, 1.1 to 2.9) early post-HCT, 1.8 points (95% CI, .3 to 3.3) after 3 months, and 1.7 points (95% CI, .0 to 3.3) after 12 months. Total body irradiation as part of the conditioning regimen and oral mucosal changes related to cGVHD did not significantly influence the severity of xerostomia. Conditioning regimen intensity was a significant risk indicator in the development of xerostomia, whereas total body irradiation was not. Allogeneic HCT recipients experienced more xerostomia than autologous HCT recipients, a difference that cannot be explained by a reduction in stimulated salivary flow rate or the development of oral mucosal changes related to cGVHD.

The effect of conditioning regimen and prescribed medications on hyposalivation in haematopoietic cell transplantation (HCT) patients: an 18-month prospective longitudinal study.

OBJECTIVES: Haematopoietic cell transplantation (HCT) preceded by a conditioning regimen is an established treatment option for (non)malignant haematologic disorders. We aim to describe the development of hyposalivation over time in HCT recipients, and determine risk indicators. MATERIALS AND METHODS: A multi-centre prospective longitudinal observational study was conducted. Unstimulated (UWS) and stimulated (SWS) whole saliva was collected before HCT, early post-HCT, and after 3, 6, 12, and 18 months. The effect of type of transplantation (allogeneic vs autologous) and intensity (full vs reduced) of the conditioning regimen on hyposalivation (UWS < 0.2 mL/min; SWS < 0.7 mL/min) was explored. RESULTS: A total of 125 HCT recipients were included. More than half of the patients had hyposalivation early post-HCT; a quarter still had hyposalivation after 12 months. The conditioning intensity was a risk indicator in the development of hyposalivation of both UWS (OR: 3.9, 95% CI: 1.6-10.6) and SWS (OR: 8.2, 95% CI: 2.9-24.6). After 3 and 12 months, this effect was not statistically significant anymore. CONCLUSIONS: Hyposalivation affects the majority of patients early post-HCT. The conditioning intensity and the type of transplantation were significant risk indicators in the development of hyposalivation. The number of prescribed medications, total body irradiation as part of the conditioning regimen and oral mucosal graft-versus-host disease did not influence hyposalivation significantly. CLINICAL RELEVANCE: Because of the high prevalence of hyposalivation, HCT recipients will have an increased risk of oral complications. It might be reasonable to plan additional check-ups in the dental practice and consider additional preventive strategies.

The effect of hematopoietic stem cell transplantation on patient-reported subjective oral dryness: a systematic review focusing on prevalence, severity and distress.

OBJECTIVE: The aim of the present systematic review is to assess the prevalence and severity of and distress caused by xerostomia over time in adult hematopoietic stem cell transplantation (HSCT) recipients. METHODS: PubMed, Embase, and the Cochrane Library were searched for papers published between January 2000 and May 2022. Clinical studies were included if patient-reported subjective oral dryness was reported in adult autologous or allogeneic HSCT recipients. Risk of bias was assessed according to a quality grading strategy published by the oral care study group of the MASCC/ISOO, resulting in a score between 0 (highest risk of bias) and 10 (lowest risk of bias). Separate analysis focused on autologous HSCT recipients, allogeneic HSCT recipients receiving a myeloablative conditioning (MAC), and those receiving a reduced intensity conditioning (RIC). RESULTS: Searches yielded 1792 unique records; 22 studies met the inclusion criteria. The quality scores ranged between 1 and 7, with a median score of 4. The prevalence, severity, and distress of xerostomia increased shortly after HSCT. Severity of xerostomia in allogeneic MAC recipients was higher compared to allogeneic RIC recipients 2-5 months post-HSCT (mean difference: 18 points on 0-100 scale, 95% CI: 9-27); after 1-2 years, there was no significant difference anymore. CONCLUSION: The prevalence of xerostomia in HSCT recipients is high in comparison to the general population. The severity of complaints is raised during the first year post-HSCT. The intensity of the conditioning plays a key role in the short-term development of xerostomia, while factors affecting the recovery in the long term remain largely unknown.

Caries, periodontitis and tooth loss after haematopoietic stem cell transplantation: A systematic review.

OBJECTIVE: A systematic review was conducted to assess scientific knowledge concerning the effect of haematopoietic stem cell transplantation (HSCT) on the occurrence of caries, periodontal conditions and tooth loss, and to evaluate the prevalence of these diseases in adult HSCT survivors (PROSPERO 152906). METHODS: PubMed and Embase were searched for papers, published from January 2000 until November 2020 without language restriction, assessing prevalence, incidence or parameters of caries, periodontal conditions and tooth loss in HSCT recipients (≥80% transplanted in adulthood). Bias risk was assessed with checklists from Joanna Briggs Institute, and data synthesis was performed by narrative summary. RESULTS: Eighteen papers were included (1618 subjects). Half were considered at high risk of bias. Longitudinal studies did not show caries progression, decline in periodontal health or tooth loss after HSCT. The prevalence in HSCT survivors ranged from 19% to 43% for caries, 11% to 67% for periodontitis, and 2% to 5% for edentulism. Certainty in the body of evidence was very low. CONCLUSIONS: Haematopoietic stem cell transplantation, on the short term, may have little to no effect on caries, periodontal conditions and tooth loss. Caries and periodontitis may be more common in HSCT survivors compared with the general population, whereas edentulism may be comparable. However, the evidence for all conclusions is very uncertain.

Caries Progression after Haematopoietic Stem Cell Transplantation and the Role of Hyposalivation.

Haematopoietic stem cell transplantation (HSCT) preceded by a conditioning regimen is an established treatment option for many haematological diseases. Decreased salivary flow rates after HSCT may increase caries risk. We aim to estimate the extent to which caries lesions develop or progress in adult HSCT recipients and assess its association with salivary flow rates. A multi-centre prospective observational study was conducted in which patients receiving HSCT were followed up for 18 months. We included 116 patients (median age 56 years, 43% female) from two medical centres in the Netherlands. Unstimulated whole saliva (UWS) and stimulated whole saliva (SWS) were collected, and full caries charts were made before HSCT and 3, 6, 12, and 18 months post-HSCT. Caries was scored according to the ICDAS criteria by trained dentist-examiners. New dentine lesions or lesion progression into dentine (ICDAS ≥4 or cavitated root lesions) occurred in 32% of patients over 18 months. The median number of affected surfaces was 2 (range: 1-12) per patient with caries progression. The influence of hyposalivation of unstimulated saliva (<0.2 mL/min) and stimulated saliva (<0.7 mL/min) at baseline and after 3 months on caries progression was determined with a negative binomial regression model. Hyposalivation of SWS 3 months after HSCT was a significant risk indicator for caries progression (incidence rate ratio: 5.30, 95% CI: 2.09-13.4, p < 0.001), while hyposalivation of SWS at baseline and hyposalivation of UWS were not. We conclude that caries progression is a common oral complication in patients after HSCT, and stimulated hyposalivation shortly after treatment is a significant risk indicator for caries progression.