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Purpose: Oral mucositis is a common complication for patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) and causes pain and difficulties in functions like eating and swallowing, resulting in lower quality of life and greater need of treatment with opioids and parenteral nutrition. This prospective multicenter study focused on pediatric recipients of HSCT in the neutropenic phase concerning oral complications, timing, severity, and patient experience., Methods: The cohort comprised 68 patients, median age 11.1 years (IQR 6.3) receiving allogeneic HSCT at three clinical sites. Medical records were retrieved for therapy regimens, concomitant medications, oral and dental history, and subjective oral complaints. Calibrated dentists conducted an oral and dental investigation before HSCT. After HSCT graft infusion, study personnel made bedside assessments and patients filled out a questionnaire once or twice a week until neutrophil engraftment., Results: We followed 63 patients through the neutropenic phase until engraftment. 50% developed oral mucositis of grades 2-4. Peak severity occurred at 8-11 days after stem cell infusion. Altogether, 87% had subjective oral complaints. The temporal distribution of adverse events is similar to the development of oral mucositis. The most bothersome symptoms were blisters and oral ulcerations, including mucositis; 40% reported severe pain and major impact on activities of daily living despite continuous use of opioids., Conclusion: This study highlights the burden of oral complications and their negative effect on the health and quality of life of HSCT recipients., (© 2023. The Author(s).)

Objectives: To determine whether treatment with tacrolimus plus sirolimus (Tac/Sir) as a prophylaxis for graft-versus-host disease worsens severe oral mucositis and delays healing compared to cyclosporine plus methotrexate (CsA/Mtx) following haematopoietic stem cell transplantation., Subjects and Methods: The study comprised 141 patients: 73 randomized to receive Tac/Sir and 68 to receive CsA/Mtx. The oral mucositis assessment scale and toxicity grading according to WHO were used to assess the severity, peak and duration of oral mucositis from the day -3 to day 24 post-transplant., Results: Eighty-seven patients developed oral mucositis in the first 24 days post-transplant. No significant difference in oral mucositis severity between the Tac/Sir and CsA/Mtx groups was observed. The peak oral mucositis score occurred on day 10 in both groups. Although oral mucositis scores had returned to baseline in the CsA/Mtx group on day 24 post-transplant, no significant difference compared with the Tac/Sir group was found., Conclusions: The introduction of tacrolimus/sirolimus as a graft-versus-host disease prophylaxis in haematopoietic stem cell transplantation increased neither the incidence nor severity of oral mucositis compared with cyclosporine/methotrexate. Furthermore, oral mucositis healing was not prolonged and followed the same time pattern as cyclosporine/methotrexate., (© 2020 The Authors. Oral Diseases published by Wiley Periodicals LLC.)

Purpose: Oral mucositis (OM) is a severe side effect of conditioning for allogeneic hematopoietic stem cell transplantation (HSCT). The aim of the present study was to investigate the relationship between oral mucositis and the levels of pro-inflammatory cytokines-both in serum and in gingival crevicular fluid (GCF), in relation to different conditioning regimens., Methods: We analyzed the levels of pro-inflammatory cytokines IL-1β, TNF-α, IL-6, and IL-7, as well as anti-inflammatory cytokine IL-10 in gingival crevicular fluid (GCF) and in serum from 43 HSCT patients. Twenty-five received reduced intensity conditioning (RIC) and 18 received myeloablative conditioning (MAC). Cytokine levels were determined in GCF and serum before the start of conditioning, and 1 week and 1 month after HSCT. All patients experienced OM with a median score of 2.1 and median peak on day 11., Results: There was a significant correlation between OM and MAC (p = 0.035). There were no significant differences in GCF volume at the three time points examined. The levels of IL-6 in GCF increased 1 week after transplantation and then returned to baseline (p < 0.001). The levels of IL-10 in GCF decreased after HSCT (p < 0.001) and remained unchanged. The levels of IL-6 in serum significantly (p < 0.001) increased 1 week after HSCT and decreased to baseline levels after 1 month. The levels of IL-10 in serum significantly (p = 0.02) increased 1 month after HSCT., Conclusion: No correlations between cytokine levels in gingival crevicular fluid and oral mucositis were observed. There was a correlation between severity of OM score and increase in IL-6 in serum. No correlations between cytokine levels in gingival crevicular fluid and in serum were observed.

Purpose: Hematology-oncology patients undergoing chemotherapy and hematopoietic stem cell transplantation (HSCT) recipients are at risk for oral complications which may cause significant morbidity and a potential risk of mortality. This emphasizes the importance of basic oral care prior to, during and following chemotherapy/HSCT. While scientific evidence is available to support some of the clinical practices used to manage the oral complications, expert opinion is needed to shape the current optimal protocols., Methods: This position paper was developed by members of the Oral Care Study Group, Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) and the European Society for Blood and Marrow Transplantation (EBMT) in attempt to provide guidance to the health care providers managing these patient populations., Results: The protocol on basic oral care outlined in this position paper is presented based on the following principles: prevention of infections, pain control, maintaining oral function, the interplay with managing oral complications of cancer treatment and improving quality of life., Conclusion: Using these fundamental elements, we developed a protocol to assist the health care provider and present a practical approach for basic oral care. Research is warranted to provide robust scientific evidence and to enhance this clinical protocol.

Purpose: Oral mucositis (OM) is a side effect of intensive chemotherapy and radiation and has been reported to affect 75-100% of hematopoietic stem cell transplantation (HSCT) recipients. The purpose of this study was to compare the incidence of OM in patients conditioned with myeloablative conditioning (MAC) to reduced-intensity conditioning (RIC) and to determine the effect of a new oral care protocol., Methods: The study involved 171 HSCT recipients, with hematological malignancies transplanted between 2007 and 2011. Median age of the patients was 50 years (range 12-71). Ninety-nine (58%) received RIC and 72 received MAC. Clinical features of OM were recorded from day -3 before to day +25 after HSCT using the World Health Organization (WHO) scoring system and the oral mucositis assessment score (OMAS)., Results: Overall, 87% of the patients developed OM of any severity, which peaked on days 10-11. The mean WHO score was 1.7. In multivariate analysis, the severity of OM was associated with MAC (relative hazard (RH) 1.57, 95% confidence interval (CI) 1.37-1.80, p < 0.001), all donor-recipient gender combinations except female-to-male (RH = 1.26, 95% CI 1.10-1.4, p = 0.001), and early year of HSCT (RH = 0.84, 95%CI 0.7-0.96, p = 0.013). There was a correlation between long hospitalization and OM (day 15, r = 0.31, p < 0.001). There was a good correlation between the WHO and OMAS scoring systems for OM (r = 0.74, p < 0.001)., Conclusions: Oral mucositis was reduced in patients treated with RIC and in patients treated during recent years, when oral care was intensified. Increased scores of OM prolonged hospitalization.

For prevention of graft-versus-host disease (GVHD), treatment of 24 haematopoietic stem cell transplantation (HSCT) patients with sirolimus and tacrolimus was compared to treatment of matched controls with cyclosporine-based regimens. The patients mainly had non-malignant disorders. Two-thirds of the donors were unrelated, and bone marrow was the most common source of stem cells. Rejection occurred in four patients in the sirolimus group and three in the control group. Donor chimerism for CD3, CD19 and CD33 was similar in the two groups. The cumulative incidence of grade II acute GVHD was 22% in the sirolimus patients and 17% in the controls (P=0.78). No patients developed acute GVHD of grades III-IV. The cumulative incidence of chronic GVHD was 25% and 37% in the two groups, respectively (P=0.40). Two patients in the sirolimus group developed Epstein-Barr virus lymphoma, and none in the controls. Side effects and toxicity were similar in the two groups. There was no transplant-related mortality at 5 yr in the sirolimus group, as opposed to 8% in the controls (P=0.47). Survival at 5 yr was 95% and 92%. Thus, sirolimus combined with tacrolimus is a promising immunosuppressive regimen in HSCT, also for non-malignancies, and its efficacy should be confirmed in prospective clinical trials., (© 2011 John Wiley & Sons A/S.)

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., (Copyright © 2011 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

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 10 Gy single dose TBI (sTBI) and cyclophosphamide (Cy) 60 mg/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 13 years of age, and had survived 2-16 years 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±0.5 ml/min in sTBI/Cy group compared to 1.1±0.6 ml/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., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

High-dose chemotherapy or chemoradiotherapy followed by hematopoietic cell transplantation (HCT) is being used for an ever increasing number of children with malignant or nonmalignant disorders, and improved results are leading to an ever increasing number of long-term survivors. Understanding the delayed effects that may occur after HCT is important in determining the evaluations to perform for this unique group of patients. The articles that follow detail what has been observed to date regarding the oral cavity and dental late effects, the kidney after HCT, and the evaluations to perform to determine late effects when patients return to the centers after their HCT.

Mesenchymal stromal cells (MSCs) are increasingly used in regenerate medicine. Placenta-derived decidual stromal cells (DSCs) are a novel therapy for acute graft-versus-host-disease (GVHD) and hemorrhagic cystitis (HC) after allogeneic hematopoietic stem cell transplantation (HSCT). DSCs are more immunosuppressive than MSCs. We assessed adverse events and safety using DSCs among 44 treated patients and 40 controls. The median dose of infused cells was 1.5 (range 0.9–2.9) × 106 DSCs/kg. The patients were given 2 (1–5) doses, with a total of 82 infusions. Monitoring ended 3 months after the last DSC infusion. Three patients had transient reactions during DSC infusion. Laboratory values, hemorrhages, and transfusions were similar in the two groups. The frequency of leukemic relapse (2/2, DSC/controls) and invasive fungal infections (6/6) were the same in the two groups. Causes of death were those seen in HSCT patients: infections (5/3), respiratory failure (1/1), circulatory failure (3/1), thromboembolism (1/0), multiorgan failure (0/1), and GVHD and others (2/7). One-year survival for the DSC patients with GVHD was 67%, which was significantly better than achieved previously at our center. One-year survival was 90% in the DSC-treated HC group. DSC infusions appear safe. Randomized studies are required to prove efficacy. [ABSTRACT FROM AUTHOR]