Extracorporeal Photopheresis versus Anticytokine Therapy as a Second-Line Treatment for Steroid-Refractory Acute GVHD: A Multicenter Comparative Analysis

AbstractThe optimal therapy for steroid-refractory (SR) acute graft-versus-host disease (aGVHD) is undefined. We studied patients with SR aGVHD, comparing extracorporeal photopheresis (ECP; n = 57) and anticytokine therapy (n = 41). In multivariate analyses, ECP, adjusted for steroid dose (odds ratio, 3.42; P = .007), and grade >II aGVHD (odds ratio, 68; P < .001) were independent predictors of response. ECP therapy, adjusted for conditioning regimen intensity and steroid dose, was associated with superior survival (hazard ratio [HR], 4.6; P = .016) in patients with SR grade II aGVHD. Grade >II aGVHD at onset of salvage therapy (HR, 9.4; P < .001) and lack of response to therapy (HR, 3.09; P = .011) were associated with inferior survival. These findings require validation in a prospective randomized study

Adiponectin and resistin in acute and chronic graft-vs-host disease patients undergoing allogeneic hematopoietic stem cell transplantation

Aim To investigate the association of adiponectin and resistin levels in patients undergoing hematopoietic stem cell transplantation (HSCT) with the clinical outcome, including the occurrence of acute and chronic graft-vs-host disease (GVHD), non-relapse mortality, and overall survival. Methods We prospectively collected serum samples from 40 patients undergoing either autologous (n = 12; 10 male) or allogeneic (n = 28; 11 male) HSCT for up to 12 months post HSCT and determined adiponectin and resistin serum concentrations using enzyme-linked immunosorbent assay. Results There were no significant differences in adiponectin levels (18.5 vs 9.3 μg/mL, P = 0.071) and adiponectin/ BMI ratio (0.82 vs 0.39, P = 0.068) between patients with acute GVHD grades 2-4 and autologous controls. However, resistin values were significantly lower in patients with acute GVHD grades 2-4 than in autologous controls (4.6 vs 7.3 ng/mL, P = 0.030). Adiponectin levels were higher in patients with chronic GVHD (n = 17) than in autologous controls (13.5 vs 7.6 μg/mL, P = 0.051), but the difference was not significant. Adiponectin/BMI ratio was significantly higher in patients with chronic GVHD than in autologous controls (0.59 vs 0.25, P = 0.006). Patients dying from relapse also had significantly lower adiponectin levels (8.2 μg/mL) and adiponectin/BMI ratio (0.3) on admission than surviving allogeneic (15.8 μg/mL, P = 0.030 and 0.7, P = 0.004) and surviving autologous patients (19.2 μg/mL, P = 0.031 and 0.7, P = 0.021). Conclusion Adiponectin and resistin levels were altered in patients with acute and chronic GVHD compared to autologous controls and were associated with overall survival and relapse mortality in patients undergoing allogeneic HSCT

Investigation and Management of Bone Mineral Density Following Hematopoietic Cell Transplantation : A Survey of Current Practice by the Transplant Complications Working Party of the European Society for Blood and Marrow Transplantation

Reduced bone mineral density (BMD) is a well-recognized complication of hematopoietic cell transplantation (HCT), with significant drops in BMD occurring within the first 12 months after HCT. Guidance on identifying and managing this complication is available in several published guidelines. In this study, we investigated current practices in the investigation and management of low BMD in centers registered with the European Society for Blood and Marrow Transplantation (EBMT). A questionnaire about bone health was sent to all registered centers, and responses were received from 99 centers in 25 countries (52%) currently registered with the EBMT. Our data highlight considerable heterogeneity in practices across European centers in relation to investigations, management, and use of guidelines. Our data demonstrate the need for better dissemination and implementation of existing guidelines and also for the development of multidisciplinary guidelines with input from all relevant stakeholders. (c) 2020 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.Peer reviewe

Use of the NIH consensus criteria in cellular and soluble biomarker research in chronic graft-versus-host disease: A systematic review

Objectives: Chronic graft-versus-host disease (cGvHD) is the most frequent cause of late non- relapse mortality after allogeneic haematopoietic stem cell transplantation (alloHCT). Nevertheless, established biomarkers of cGvHD are still missing. The National Institutes of Health (NIH) Consensus Development Project on Criteria for Clinical Trials in cGvHD provided recommendations for biomarker research. We evaluated to which extent studies on cellular and soluble biomarkers in cGvHD published in the last 10 years complied with these recommendations. Also, we highlight the most promising biomarker candidates, verified in independent cohorts and/or repeatedly identified by separate studies. Methods: We searched Medline and EMBASE for “cGvHD”, “biomarkers”, “soluble” and “cells” as MeSH terms or emtree subject headings, and their variations on July 28th, 2021, limited to human subjects, English language and last ten years. Reviews, case reports, conference abstracts and single nucleotide polymorphism studies were excluded. Criteria based on the set of recommendations from the NIH group for biomarker research in cGvHD were used for scoring and ranking the references. Results: A total of 91 references encompassing 15, 089 participants were included, 54 prospective, 17 retrospective, 18 cross-sectional, and 2 studies included both prospective and retrospective cohorts. Thirty-five papers included time-matched controls without cGvHD and 20 studies did not have any control subjects. Only 9 studies were randomized, and 8 were multicentric. Test and verification cohorts were included in 11 studies. Predominantly, diagnostic biomarkers were explored (n=54). Assigned scores ranged from 5-34. None of the studies fulfilled all 24 criteria (48 points). Nevertheless, the scores improved during the last years. Three cell subsets (CXCR3+CD56bright NK cells, CD19+CD21low and BAFF/CD19+ B cells) and several soluble factors (BAFF, IL-15, CD163, DKK3, CXCL10 and the panel of ST2, CXCL9, MMP3 and OPN) had the highest potential as diagnostic and/or prognostic biomarkers in cGvHD. Conclusion: Despite several limitations of this review (limited applicability for paediatric population, definition of verification, missing data on comorbidities), we identified promising candidate biomarkers for further evaluation in multicentre collaborative studies. This review confirms the importance of the NIH consensus group criteria for improving the quality and reproducibility of cGvHD biomarker research

Rabbit ATG/ATLG in preventing graft-versus-host disease after allogeneic stem cell transplantation: consensus-based recommendations by an international expert panel

This collaborative initiative aimed to provide recommendations on the use of polyclonal antithymocyte globulin (ATG) or anti-T lymphocyte globulin (ATLG) for the prevention of graft-versus-host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (HSCT). A comprehensive review of articles released up to October, 2018 was performed as a source of scientific evidence. Fourteen clinically relevant key questions to the domains indication, administration, and post-transplant management were developed and recommendations were produced using the Delphi technique involving a Panel of 14 experts. ATG/ATLG was strongly recommended as part of myeloablative conditioning regimen prior to matched or mismatched unrelated bone marrow or peripheral blood allogeneic HSCT in malignant diseases to prevent severe acute and chronic GvHD. ATG/ATLG was also recommended prior to HLA-identical sibling peripheral HSCT with good but lesser bulk of evidence. In reduced intensity or nonmyeloablative conditioning regimens, ATG/ATLG was deemed appropriate to reduce the incidence of acute and chronic GvHD, but a higher risk of relapse should be taken into account. Recommendations regarding dose, application, and premedication were also provided as well as post-transplant infectious prophylaxis and vaccination. Overall, these recommendations can be used for a proper and safe application of polyclonal ATG/ATLG to prevent GvHD after allogeneic HSCT

Validation of the Human Activity Profile Questionnaire in Patients after Allogeneic Hematopoietic Stem Cell Transplantation

Chronic graft-versus-host disease (cGVHD) associated morbidity and mortality remain major barriers for successful allogeneic hematopoietic stem cell transplantation (alloHSCT). Currently, no reliable measures are established to monitor cGVHD activity changes for use in clinical trials. The Human Activity Profile (HAP) patient self-report was proposed by the National Institutes of Health (NIH) cGVHD consensus project as an independent measure of patients' functional status that could also indirectly reflect improvement of cGVHD, but that has not been validated in an alloHSCT patient population. One hundred seventy-six patients (median age 44 years [range: 18-72 years] after alloHSCT were evaluated with a German translation of the HAP, the NIH criteria-based cGVHD activity assessment, the Lee cGVHD Symptom-Scale, FACT-BMT, SF36, Berlin Social Support Scale, 24-Item Adjective Measure (24-AM), Hospital Anxiety and Depression Scale, and the NCCN-Distress-Thermometer. Enrollment occurred a median of 286 (range: 85-4003) days after alloHSCT. Follow-up surveys were conducted at 1, 2, 3, 5, 8, and 12 months after the baseline survey. Although 117 patient had cGVHD at time of enrollment (mild n = 33, moderate n = 50, or severe n = 34), 59 patients were included into the study in the absence of cGVHD between days 85 and 395 after transplantation. The maximum activity score (MAS) and adjusted activity score (AAS) of the HAP correlated inversely with grading of cGVHD severity (mild, moderate, or severe) (r = −0.25 for MAS and −0.24 for AAS). Lung manifestations of cGVHD correlated with AAS (r = 0.17), but not with MAS. HAP scores correlated with subscales from other instruments measuring physical domains, especially the physical functioning scale of the SF36. Performance was improved by use of an HSCT-modified HAP scoring system that excluded activities prohibited within the first year after alloHSCT. No significant correlation of the HAP was found with personality, age, sex, symptom burden, or social functioning or social well-being. Moreover, the HAP displayed a higher sensitivity to change of cGVHD activity compared to the SF36 and the FACT-BMT. In addition, steroid myopathy correlated with both HAP scores, but not the SF36. The HAP is a simple and valid questionnaire for the evaluation of the physical activity in patients after alloHSCT, with the advantage of detecting changes in cGVHD status independently of other quality-of-life measures and with a superior sensitivity compared to the SF36

Cost and quality issues in establishing hematopoietic cell transplant program in developing countries

The hematopoietic cell transplant (HCT) activity has grown significantly over the past two decades in both developing and developed countries. Many challenges arise in establishing new HCT programs in developing countries, due to scarcity of resources and manpower in expertise in HCT. While cost issues can potentially hinder establishment of new HCT programs in certain regions, the focus on quality and value should be included in the general vision of leadership before establishing an HCT program. The main challenge in most developing countries is the lack of trained/qualified personnel, enormous start-up costs for a tertiary care center, and quality maintenance. Herein, we discuss the main challenges from a cost and quality perspective which occur at initiation of a new HCT program. We give real world examples of two developing countries that have recently started new HCT programs despite significant financial constraints. We also portray recommendations from the Worldwide Network of Blood and Marrow Transplantation for levels of requirements for a new HCT program. We hope that this review will serve as a general guide for new transplant program leadership with respect to the concerns of balancing high quality with concurrently lowering costs