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

Abstract

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.

Keywords: Haematopoietic cell transplantation; Hyposalivation; Medications; Salivary flow rate.

Fig. 1

Flowchart of the study. A distinction is made between patients treated at Amsterdam UMC, location AMC (A) and Radboudumc (R). Reasons for exclusion and irreversible loss to follow-up are shown in the grey squares on the left and right side of this diagram. In 12 patients, no saliva was collected early post-HCT because patients were ill/nauseous (n = 5), the hospital stay was too short (n = 6), or unknown reasons (n = 1). Reasons for 26 incidental missed appointments in 23 patients during the long-term follow-up, marked with asterisk in this diagram were the following: unable to come due to hospitalisation, rehabilitation, or illness (n = 4), refused to come or did not come (n = 10), unreachable (n = 3), or other/unknown reasons (n = 9)

Fig. 2

Prevalence of hyposalivation over time. Numbers (n) are the numbers of patients that contributed one or more saliva samples per time point or period. Five SWS samples in two patients are missing due to prosthesis, and 2 UWS samples in one patient are missing due to chewing gum use preceding the collection. Furthermore, several patients felt too ill or nauseous, or experienced too much pain in the oral cavity to collect SWS early post-HCT. Abbreviations: UWS, unstimulated whole saliva; SWS, stimulated whole saliva; MAC, myeloablative conditioning; NMA/RIC, non-myeloablative or reduced intensity conditioning

Fig. 3

Mean salivary unstimulated whole saliva (UWS, a) and salivary stimulated whole saliva (SWS, b) flow rates with standard deviations (SD) over time. Numbers of patients (n) who contributed saliva sample(s) per time point or period are listed below the graphs. Abbreviations: MAC, myeloablative conditioning; NMA/RIC, non-myeloablative or reduced intensity conditioning

Fig. 4

Mean number of prescribed medications during the week preceding the pre-conditioning screening (a), and during the hospitalisation phase (b). Numbers of patients (n) are listed below the graph. Autologous HCT recipients stayed for median 19 days (range: 15–32) in the hospital, allogeneic myeloablative (MAC) recipients for 24 days (range: 17–33), reduced intensity (RIC) for 24.5 days (range 20–35), and non-myeloablative (NMA) for 16 days (range 14–23)

Fig. 5

Venn diagram showing the diagnoses of hyposalivation of stimulated whole saliva (SWS), unstimulated whole saliva (UWS), and oral mucosal chronic graft-versus-host disease (cGvHD)

Fig. 6

The relation between several risk indicators and hyposalivation. Hyposalivation of unstimulated whole saliva (UWS) is shown on the left side, hyposalivation of stimulated whole saliva (SWS) on the right side. Odds ratios (OR) are shown with their 95% confidence interfalls. a Relation between intensity of the conditioning regimen and hyposalivation at different moments in time Myeloablative conditioning regimens are compared to non-myeloablative or reduced intensity (NMA/RIC) conditioning regimens. In the adjusted model, the following variables were added: hyposalivation at baseline (UWS and SWS respectively), total body irradiation, and age. b Relation between total body irradiation (TBI) as part of the conditioning regimen and hyposalivation at different moments in time. In the adjusted model, the following variables were added: hyposalivation at baseline (UWS and SWS respectively), the intensity of the conditioning regimen and age. c The relation between the type of transplantation (allogeneic vs autologous) and hyposalivation at different moments in time. In the adjusted model, the following variables were added: the intensity of the conditioning regimen, hyposalivation at baseline (UWS and SWS respectively) and age. d Relation between hyposalivation and oral mucosal changes related to chronic graft-versus-host disease (cGvHD) at the same follow-up. In the adjusted model, the following variables were added: hyposalivation at baseline (UWS and SWS respectively), the intensity of the conditioning regimen and age. e The relation between the number of prescribed medications during hospitalisation and hyposalivation early post-HCT. In the adjusted model, the following variables were added: the intensity of the conditioning regimen, hyposalivation at baseline (UWS and SWS respectively), length of hospital stay in days and age

Fig. 6

The relation between several risk indicators and hyposalivation. Hyposalivation of unstimulated whole saliva (UWS) is shown on the left side, hyposalivation of stimulated whole saliva (SWS) on the right side. Odds ratios (OR) are shown with their 95% confidence interfalls. a Relation between intensity of the conditioning regimen and hyposalivation at different moments in time Myeloablative conditioning regimens are compared to non-myeloablative or reduced intensity (NMA/RIC) conditioning regimens. In the adjusted model, the following variables were added: hyposalivation at baseline (UWS and SWS respectively), total body irradiation, and age. b Relation between total body irradiation (TBI) as part of the conditioning regimen and hyposalivation at different moments in time. In the adjusted model, the following variables were added: hyposalivation at baseline (UWS and SWS respectively), the intensity of the conditioning regimen and age. c The relation between the type of transplantation (allogeneic vs autologous) and hyposalivation at different moments in time. In the adjusted model, the following variables were added: the intensity of the conditioning regimen, hyposalivation at baseline (UWS and SWS respectively) and age. d Relation between hyposalivation and oral mucosal changes related to chronic graft-versus-host disease (cGvHD) at the same follow-up. In the adjusted model, the following variables were added: hyposalivation at baseline (UWS and SWS respectively), the intensity of the conditioning regimen and age. e The relation between the number of prescribed medications during hospitalisation and hyposalivation early post-HCT. In the adjusted model, the following variables were added: the intensity of the conditioning regimen, hyposalivation at baseline (UWS and SWS respectively), length of hospital stay in days and age