Association of uric acid levels before start of conditioning with mortality after allogeneic hematopoietic stem cell transplantation - a prospective, non-interventional study of the EBMT Transplant Complication Working Party

Uric acid is a danger signal contributing to inflammation. Its relevance to allogeneic stem cell transplantation (alloSCT) derives from preclinical models where the depletion of uric acid led to improved survival and reduced graft-versus-host disease (GvHD). In a clinical pilot trial, peri-transplant uric acid depletion reduced acute GvHD incidence. This prospective international multicenter study aimed to investigate the association of uric acid serum levels before start of conditioning with alloSCT outcome. We included patients with acute leukemia, lymphoma or myelodysplastic syndrome receiving a first matched sibling alloSCT from peripheral blood, regardless of conditioning. We compared outcomes between patients with high and low uric acid levels with univariate- and multivariate analysis using a cause-specific Cox model. Twenty centers from 10 countries reported data on 366 alloSCT recipients. There were no significant differences in terms of baseline co-morbidity and disease stage between the high- and low uric acid group. Patients with uric acid levels above median measured before start of conditioning did not significantly differ from the remaining in terms of acute GvHD grades II-IV incidence (Hazard ratio [HR] 1.5, 95% Confidence interval [CI]: 1.0-2.4, P=0.08). However, they had significantly shorter overall survival (HR 2.8, 95% CI: 1.7-4.7, PPeer reviewe

Addition of Rituximab in Reduced Intensity Conditioning Regimens for B-Cell Malignancies Does Not Influence Transplant Outcomes: EBMT Registry Analyses Following Allogeneic Stem Cell Transplantation for B-Cell Malignancies

Rituximab (R) is increasingly incorporated in reduced intensity conditioning (RIC) regimens for allogeneic hematopoietic cell transplantation (alloHCT) in patients with B-cell malignancies, not only to improve disease control, but also to prevent graft-versus-host disease (GVHD). There are no randomized prospective data to validate this practice, although single center data and the CIBMTR analysis have shown promising results. We aimed at validation of these findings in a large registry study. We conducted a retrospective analysis using the EBMT registry of 3,803 adult patients with B-cell malignancies undergoing alloHCT (2001–2013) with either rituximab (R-RIC-9%) or nonrituximab (RIC-91%) reduced intensity regimens respectively. Median age and median follow up were 55 years (range 19.1–77.3) and 43.2 months (range 0.3–179.8), respectively. There was no difference in transplant outcomes (R-RIC vs RIC), including 1-year overall survival (69.9% vs 70.7%), 1-year disease-free survival (64.4% vs 62.2%), 1-year non-relapse mortality (21% vs 22%), and day-100 incidence of acute GVHD 2-4° (12% vs 12%). In summary, we found that addition of rituximab in RIC regimens for B-cell malignancies had no significant impact on major transplant outcome variables. Of note, data on chronic GVHD was not available, limiting the conclusions that can be drawn from the present study

Practice patterns in chronic graft-versus-host disease patient management and patient reported outcome measures across the EBMT allogeneic transplantation network

Background Chronic graft-versus-host disease (cGvHD) is one of the most common life-threatening complications following allogeneic haematopoietic stem cell transplantation (alloHSCT). Understanding outcome after alloHSCT requires a full evaluation of the patient’s health status, including cGvHD and patient reported outcomes (PROs). In an effort to better understand practice patterns across European countries, a survey was initiated by the Integrated European Network on cGvHD (an EU-funded COST Action CA17138 EUROGRAFT, www.gvhd.eu) and the Transplant Complications Working Party of the European Society for Blood and Marrow Transplantation (EBMT). This report shares results of the survey, offering a snapshot view of current practice patterns in the context of long-term care of cGvHD patients. Methods Our self-designed 38-item online survey (Supplementary Material) was intended to collect data regarding transplant center characteristics, data registration practices, the use of NIH criteria in clinical routine, biopsies/biomarkers for clinical assessment, cGvHD cell-based therapies, and PROs. The survey used computer adapted testing methods and took ~10 min to complete. All centers participating in the COST Action EUROGRAFT and all EBMT centers performing alloHSCT were invited by email for participation in the survey. Data were collected between July 2019 and July 2020. Appropriate descriptive statistics were used. In case of multiple entries for a single center (n = 4), only the entry from the most senior staff member was included for the analysis. Missing data was reported as such. Findings Center characteristics Survey results are summarized in Table 1. A total of 72 centers out of 424 invited centers from 24 countries responded to the survey, representing ~17% of all alloHSCT centers and 19.6% of all transplanted patients within the EBMT network [1]. The majority of participating alloHSCT centers were from Europe with exception of three centers based in Asia and one in Latin America. Survey responses were mainly submitted by physicians and data managers. Of note, the size of the transplant programs differed between responding (mean ± SD, n = 47 ± 40 transplants/year) vs. non-responding (mean ± SD, n = 39 ± 31 transplants/year) centers (Supplementary Material)

Improved survival after acute graft-

A cute graft- versus -host disease remains a major threat to a successful outcome after allogeneic hematopoietic cell transplantation. While improvements in treatment and supportive care have occurred, it is unknown whether these advances have resulted in improved outcome specifically among those diagnosed with acute graft- versus -host disease. We examined outcome following diagnosis of grade II-IV acute graft- versus -host disease according to time period, and explored effects according to original graft- versus -host disease prophylaxis regimen and maximum overall grade of acute graft- versus -host disease. Between 1999 and 2012, 2,905 patients with acute myeloid leukemia (56%), acute lymphoblastic leukemia (30%) or myelodysplastic syndromes (14%) received a sibling (24%) or unrelated donor (76%) blood (66%) or marrow (34%) transplant and developed grade II-IV acute graft- versus -host disease (n=497 for 1999-2001, n=962 for 2002-2005, n=1,446 for 2006-2010). The median (range) follow-up was 144 (4-174), 97 (4-147) and 60 (8-99) months for 1999-2001, 2002-2005, and 2006-2010, respectively. Among the cohort with grade II-IV acute graft- versus -host disease, there was a decrease in the proportion of grade III-IV disease over time with 56%, 47%, and 37% for 1999-2001, 2002-2005, and 2006-2012, respectively ( P <0.001). Considering the total study population, univariate analysis demonstrated significant improvements in overall survival and treatment-related mortality over time, and deaths from organ failure and infection declined. On multivariate analysis, significant improvements in overall survival ( P =0.003) and treatment-related mortality ( P =0.008) were only noted among those originally treated with tacrolimus-based graft- versus -host disease prophylaxis, and these effects were most apparent among those with overall grade II acute graft- versus -host disease. In conclusion, survival has improved over time for tacrolimus-treated transplant recipients with acute graft- versus -host disease

"This Graft-vs.-Host Disease Determines My Life. That's It."-A Qualitative Analysis of the Experiences and Needs of Allogenic Hematopoietic Stem Cells Transplantation Survivors in Germany

Initial funding for this study was provided by a grant of the Jose Carreras Leukemia Foundation (DJCLS 01 FN/2018). This work was supported by the European Cooperation in Science & Technology under the COST Action CA17138 (Integrated European Network on Chronic Graft vs. Host Disease: EUROGRAFT) (https://www.gvhd.eu). Infrastructure support was provided by the University of Regensburg and the University Hospital Regensburg.We thank the survivors and partners who participated in this study for their time and efforts. We also acknowledge the support provided by the clinic staff, particularly by the members of the Brückenpflege. Funding. Initial funding for this study was provided by a grant of the Jose Carreras Leukemia Foundation (DJCLS 01 FN/2018). This work was supported by the European Cooperation in Science & Technology under the COST Action CA17138 (Integrated European Network on Chronic Graft vs. Host Disease: EUROGRAFT) (https://www.gvhd.eu). Infrastructure support was provided by the University of Regensburg and the University Hospital Regensburg.Background: Allogeneic hematopoietic stem cell transplantation (alloHSCT) is the only curative treatment modality for many patients affected by hematologic malignancies. However, it can cause debilitating long-term effects. Understanding the impact of alloHSCT on all aspects of the patients' life is required for optimal survivorship management. Aim: To explore in-depth HSCT-survivors' experiences and needs post-transplant. Partners were included to provide further information on survivors' needs and how care could be improved in this area. Methods: We conducted semi-structured face-to-face and phone interviews with alloHSCT-survivors and their partners referred to a survivorship clinic in Germany. Theoretical sampling was used to recruit participants. Data were analyzed using framework analysis. Results: Thirty-two survivors (consent rate: 100%, response rate: 100%) and eighteen partners (consent rate: 84%, response rate: 72%) participated. Survivors were aged between 25 and 68 years (Median: 48, IQR: 25.3) and partners were aged between 26 and 64 years (Median: 54, IQR: 16, SD: 12.8). The themes emerging from the data involved survivors' needs included (i) the diversity of long-term treatment side-effects; and (ii) time post discharge as a dynamic process with individual peaks of burden. Survivors and their partners also suggested strategies for mitigating these unmet needs, i.e., (iii) transparent communication and patient empowerment; and (iv) improvement in continuity of care system and help with claiming social benefits as cornerstones of optimal survivorship care. Conclusion: To our knowledge, this is one of the first qualitative studies focused on the views of German alloHSCT-survivors on the long-term effects of alloHSCT and the first study integrating the view of their partners. Healthcare providers could better support survivors with managing their symptoms and adhering to their prescribed care by ensuring comprehensive, transparent communication that helps increase survivors' understanding and involvement in their care. Further efforts should be made to provide patient-centered, continuous survivorship care that involves additional support with navigating the healthcare and social service system. Intervention studies are required to test the effectiveness of the suggested strategies

Evaluation of the Cost of Survivorship Care After Allogeneic Hematopoeitic Stem Cell Transplantation–An Analysis of 2 German Transplantation Centers

The aim of the presented study was to analyze the care expenditure for outpatients after allogeneic hematopoietic stem cell transplantation (alloHSCT) done in accordance with the national, European guidelines and the German Social Law. We performed an analysis of the National and European survivorship care guidelines and in parallel recorded the time expenditure and staff costs separated according to different occupational groups involved in outpatient care at two German transplantation centers [University Hospital Regensburg (UKR) and University Hospital Hamburg-Eppendorf (UKE)]. In addition, we performed a comparison of real costs vs. reimbursed costs according to the standard rating benchmark catalog (EBM), which was supplemented by a survey of German transplantation centers. The results showed that the staff costs are only covered by the EBM for patients without complications during long-term follow-up care-notably, this accounts for 15% of alloHSCT patients. Staff costs for patients requiring treatment of graft-vs.-host disease or relapse of the malignant underlying malignancy exceed to the factor 6.5 (UKR) to 12 (UKE) of the EBM revenue, caused both by the increased duration and frequency of the outpatient visits. As a result of the survey at German transplant centers, 15 out of 18 responding centers reported a lack of cost coverage for follow-up care. Two/15 centers reported that survivorship care is limited to a restricted time, independent of patient's needs, due to a lack of cost reimbursement. The results show that alloHSCT survivorship care of patients requires significant staff resources, which are not covered by the current version of the German EBM catalog. New approaches to finance labor intensive after care of transplant patients are required

Association of Serum Ferritin Levels Before Start of Conditioning With Mortality After alloSCT - A Prospective, Non-interventional Study of the EBMT Transplant Complications Working Party

Contains fulltext : 219002.pdf (publisher's version ) (Open Access

Association of uric acid levels before start of conditioning with mortality after allogeneic hematopoietic stem cell transplantation - a prospective, non-interventional study of the EBMT Transplant Complication Working Party

Contains fulltext : 221430.pdf (publisher's version ) (Open Access