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- Bulthuis, Marjolein S., et al.
(författare)
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Subjective Oral Dryness following Hematopoietic Cell Transplantation: A Report from the Orastem Study
- 2024
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Ingår i: TRANSPLANTATION AND CELLULAR THERAPY. - 2666-6375 .- 2666-6367. ; 30:4
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Tidskriftsartikel (refereegranskat)abstract
- 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, 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 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) 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 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.
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| 2. |
- Mougeot, Jean-Luc C., et al.
(författare)
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Single nucleotide polymorphisms conferring susceptibility to leukemia and oral mucositis: a multi-center pilot study of patients prior to conditioning therapy for hematopoietic cell transplant
- 2024
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Ingår i: SUPPORTIVE CARE IN CANCER. - 0941-4355 .- 1433-7339. ; 32:4
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Tidskriftsartikel (refereegranskat)abstract
- PurposeLeukemias have been associated with oral manifestations, reflecting susceptibility to cancer therapy-induced oral mucositis. We sought to identify SNPs associated with both leukemia and oral mucositis (OM).MethodsWhole exome sequencing was performed on leukemia and non-cancer blood disorder (ncBD) patients' saliva samples (N = 50) prior to conditioning therapy. WHO OM grading scores were determined: moderate to severe (OM2-4) vs. none to mild (OM0-1). Reads were processed using Trim Galorev0.6.7, Bowtie2v2.4.1, Samtoolsv1.10, Genome Analysis Toolkit (GATK)v4.2.6.1, and DeepVariantv1.4.0. We utilized the following pipelines: P1 analysis with PLINK2v3.7, SNP2GENEv1.4.1 and MAGMAv1.07b, and P2 [leukemia (N = 42) vs. ncBDs (N = 8)] and P3 [leukemia + OM2-4 (N = 18) vs. leukemia + OM0-1 (N = 24)] with Z-tests of genotypes and protein-protein interaction determination. GeneCardsSuitev5.14 was used to identify phenotypes (P1 and P2, leukemia; P3, oral mucositis) and average disease-causing likelihood and DGIdb for drug interactions. P1 and P2 genes were analyzed with CytoScape plugin BiNGOv3.0.3 to retrieve overrepresented Gene Ontology (GO) terms and Ensembl's VEP for SNP outcomes.ResultsIn P1, 457 candidate SNPs (28 genes) were identified and 21,604 SNPs (1016 genes) by MAGMAv1.07b. Eighteen genes were associated with "leukemia" per VarElectv5.14 analysis and predicted to be deleterious. In P2 and P3, 353 and 174 SNPs were significant, respectively. STRINGv12.0 returned 77 and 32 genes (C.L. = 0.7) for P2 and P3, respectively. VarElectv5.14 determined 60 genes from P2 associated with "leukemia" and 11 with "oral mucositis" from P3. Overrepresented GO terms included "cellular process," "signaling," "hemopoiesis," and "regulation of immune response."ConclusionsWe identified candidate SNPs possibly conferring susceptibility to develop leukemia and oral mucositis.
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