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• This is a large cohort analysis defining oral mucosal chronic graft-versus-host disease (cGVHD) histology. • A formalized histological grading tool is described. • Histology is correlated with clinical staging to define oral mucosal cGVHD criteria. • Grades II to IV define pathological diagnostics of oral mucosal cGVHD. • Patients are stratified into groups for improved diagnostics and tailored treatments. Graft-versus-host disease (GVHD) can manifest as acute or chronic complications in patients after hematopoietic cell transplantation (HCT). Oral chronic GVHD (cGVHD) occurs in approximately 70% of HCT recipients and includes lichenoid-like mucosal reactions, restricted mouth opening, and salivary gland dysfunction. However, the underlying histopathological presentation remains to be validated in large cohorts. We characterized the histopathological features of oral mucosal cGVHD and devised a scoring model in a large patient cohort (n = 112). Oral mucosal biopsy sections (n = 303) with and without oral cGVHD were identified from archived and current HCT recipients with additional healthy controls. Histological screening was performed on hematoxylin and eosin-stained and periodic acid-Schiff-stained sections. A points-based grading tool (0 to 19, grade 0 to IV) was established based on intraepithelial lymphocytes and band-like inflammatory infiltrate, atrophic epithelium with basal cell liquefaction degeneration, including apoptosis, as well as separation of epithelium and pseudo-rete ridges. Validation involved 62 biopsy specimens, including post-HCT (n = 47) and healthy (n = 15) specimens. Remaining biopsy specimens (n = 199) were blindly graded by 3 observers. Histological severity was correlated with clinical diagnostic and distinctive features, demonstrating a spectrum of individual patient severity, including frequent signs of subclinical GVHD in healthy mucosa. However, oral cGVHD presented with significantly higher (P <.001) scores compared with HCT controls, with moderate to high positive likelihood ratios for inflammatory infiltrate, exocytosis, and basal membrane alterations. The grade II-IV biopsy specimens demonstrated a histopathological diagnosis of active mucosal lichenoid-like cGVHD, highlighting the importance of correlating clinical presentation with the dynamic histopathological processes for improved patient stratification. In addition, this tool could be used for assessing treatments, pathological processes, and immune cellular content to provide further insight into this debilitating disease. [ABSTRACT FROM AUTHOR]

We analyzed the outcome of allogeneic hematopoietic stem cell transplantation (HSCT) over the past 2 decades. Between 1992 and 2009, 953 patients were treated with HSCT, mainly for a hematologic malignancy. They were divided according to 4 different time periods of treatment: 1992 to 1995, 1996 to 2000, 2001 to 2005, and 2006 to 2009. Over the years, many factors have changed considerably regarding patient age, diagnosis, disease stage, type of donor, stem cell source, genomic HLA typing, cell dose, type of conditioning, treatment of infections, use of granulocyte-colony stimulating factor (G-CSF), use of mesenchymal stem cells, use of cytotoxic T cells, and home care. When we compared the last period (2006-2009) with earlier periods, we found slower neutrophil engraftment, a higher incidence of acute graft-versus-host disease (aGVHD) of grades II-IV, and less chronic GVHD (cGHVD). The incidence of relapse was unchanged over the 4 periods (22%-25%). Overall survival (OS) and transplant-related mortality (TRM) improved significantly in the more recent periods, with the best results during the last period (2006-2009) and a 100-day TRM of 5.5%. This improvement was also apparent in a multivariate analysis. When correcting for differences between the 4 groups, the hazard ratio for mortality in the last period was 0.59 (95% confidence interval [CI]: 0.44-0.79; P < .001) and for TRM it was 0.63 (CI: 0.43-0.92; P = .02). This study shows that the combined efforts to improve outcome after HSCT have been very effective. Even though we now treat older patients with more advanced disease and use more alternative HLA nonidentical donors, OS and TRM have improved. The problem of relapse still has to be remedied. Thus, several different developments together have resulted in significantly lower TRM and improved survival after HSCT over the last few years. [ABSTRACT FROM AUTHOR]

Summary: To study salivary secretion rates and symptoms of xerostomia in children and adolescents conditioned with either radiation therapy or with chemotherapy only in the setting of hematopoietic stem cell transplantation (HSCT). Thirty patients conditioned with 10Gy single dose TBI (sTBI) and cyclophosphamide (Cy) 60mg/kg for two days and 35 conditioned busulfan (Bu) and Cy as part of the preparative regimen were included in the study. All patients were treated before 13years of age, and had survived 2–16years after HSCT. All patients were interviewed according to a standard questionnaire on symptoms of xerostomia and the unstimulated and stimulated whole salivary secretion rate was determined. The stimulated salivary secretion rates were 0.8±0.5ml/min in sTBI/Cy group compared to 1.1±0.6ml/min in the Bu/Cy group (p =0.01). Dysfunction of either unstimulated or stimulated salivary secretion rates were found in 18/30 (60%) in sTBI/Cy group and 9/35 (26%) in Bu/Cy group (p <0.01). There were no differences regarding the number of xerostomia related symptoms in children conditioned with either sTBI/Cy or Bu/Cy. Both unstimulated and stimulated salivary secretion rates were inversely correlated to the total number of complaints of xerostomia. This study shows that children exhibit xerostomia after HSCT irrespective of conditioning with busulfan or sTBI. It is of importance that salivary function is evaluated and that both salivary function as well as the subjective feeling of mouth dryness is evaluated. [ABSTRACT FROM AUTHOR]