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1.
Prophylaxis and management of graft-versus-host disease after stem-cell transplantation for haematological malignancies: updated consensus recommendations of the European Society for Blood and Marrow Transplantation
Penack, O., Marchetti, M., Aljurf, M., Arat, M., Bonifazi, F., Duarte, R. F., Giebel, S., Greinix, H., Hazenberg, M. D., Kröger, N., et al
The Lancet. Haematology. 2024
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Editor's Choice
Abstract
Graft-versus-host disease (GVHD) is a major factor contributing to mortality and morbidity after allogeneic haematopoietic stem-cell transplantation (HSCT). In the last 3 years, there has been regulatory approval of new drugs and considerable change in clinical approaches to prophylaxis and management of GVHD. To standardise treatment approaches, the European Society for Blood and Marrow Transplantation (EBMT) has updated its clinical practice recommendations. We formed a panel of one methodologist and 22 experts in the field of GVHD management. The selection was made on the basis of their role in GVHD management in Europe and their contributions to the field, such as publications, presentations at conferences, and other research. We applied the GRADE process to ten PICO (patient, intervention, comparator, and outcome) questions: evidence was searched for by the panel and graded for each crucial outcome. In two consensus meetings, we discussed the evidence and voted on the wording and strengths of recommendations. Key updates to the recommendations include: (1) primary use of ruxolitinib in steroid-refractory acute GVHD and steroid-refractory chronic GVHD as the new standard of care, (2) use of rabbit anti-T-cell (thymocyte) globulin or post-transplantation cyclophosphamide as standard GVHD prophylaxis in peripheral blood stem-cell transplantations from unrelated donors, and (3) the addition of belumosudil to the available treatment options for steroid-refractory chronic GVHD. The EBMT proposes to use these recommendations as the basis for routine management of GVHD during allogenic HSCT. The current recommendations favour European practice and do not necessarily represent global preferences.
PICO Summary
Population
Panel of 22 experts and one methdologist convened by the European Society for Blood and Marrow Transplantation (EBMT)
Intervention
Update of the EBMT consensus recommendations
Comparison
Outcome
Key updates to the recommendations include: (1) primary use of ruxolitinib in steroid-refractory acute GVHD and steroid-refractory chronic GVHD as the new standard of care, (2) use of rabbit anti-T-cell (thymocyte) globulin or post-transplantation cyclophosphamide as standard GVHD prophylaxis in peripheral blood stem-cell transplantations from unrelated donors, and (3) the addition of belumosudil to the available treatment options for steroid-refractory chronic GVHD.
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2.
Chronic gvhd dictionary-eurograft cost action initiative consensus report
Zelić Kerep, A., Olivieri, A., Schoemans, H., Lawitschka, A., Halter, J., Pulanic, D., Dickinson, A., Greinix, H. T., Pavletic, S. Z., Schultz, K. R., et al
Bone marrow transplantation. 2022
Abstract
Chronic graft versus host disease (cGVHD) affects patients after allogeneic hematopoietic stem cell transplantation (alloHSCT). This orphan disease poses a challenge for clinicians and researchers. The purpose of the cGVHD Dictionary is to provide a standardized structure for cGVHD databases on an international level, reconciling differences in data retrieval and facilitate database merging. It is derived from several consensus meetings of the EUROGRAFT consortium (European Cooperation in Science and Technology-COST Action CA17138) followed by a consensus process involving European Society for Blood and Marrow Transplantation (EBMT), US GvHD consortium and Center for International Bone Marrow Transplant Registry (CIBMTR). Databases used for the dictionary were: the National Institutes of Health (NIH) database, the Center for International Blood and Marrow Transplant Research, Applying Biomarkers to Minimize Long Term Effects of Childhood/Adolescent Cancer Treatment - Pediatric Blood and Marrow Transplant Consortium database, EBMT registry, the German-Austrian-Swiss GvHD registry, Italian Blood and Marrow Transplantation Society registry and Regensburg-Göttingen-Newcastle HSCT dataset. A four-part cGVHD Dictionary was formed based on the databases, consensus, and evidence in the literature. The Dictionary is divided into: (1) Patient characteristics, (2) Transplant characteristics, (3) cGVHD characteristics and (4) patient-reported quality of life, symptom burden and functional indicators.
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3.
Guidelines for the Prevention and Management of Graft-versus-Host Disease after Cord Blood Transplantation
Ponce, D. M., Politikos, I., Alousi, A., Carpenter, P. A., Milano, F., MacMillan, M. L., Barker, J. N., Horwitz, M. E.
Transplantation and cellular therapy. 2021;27(7):540-544
Abstract
The incidence of graft-versus-host disease (GVHD) after cord blood (CB) transplantation (CBT) is lower than expected given the marked degree of human leukocyte antigen (HLA)-mismatch of CB grafts. While the exact mechanism that underlies this biology remains unclear, it is hypothesized to be due to the low number of mostly immature T-cells infused as part of the graft1,2, and increased tolerance of CB-derived lymphocytes induced by the state of pregnancy. Nevertheless, acute GVHD (aGVHD) is a significant complication of CBT. In contrast, the incidence of chronic GVHD (cGVHD) following CBT is lower than what is observed following matched related or unrelated donor HSC transplantation (HSCT)3-6. This review outlines the guidelines for the prevention and management of acute and chronic GVHD following CBT.
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4.
National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2020 Etiology and Prevention Working Group Report
Williams, K. M., Inamoto, Y., Im, A., Hamilton, B., Koreth, J., Arora, M., Pusic, I., Mays, J. W., Carpenter, P. A., Luznik, L., et al
Transplantation and cellular therapy. 2021
Abstract
Preventing chronic graft-versus-host disease (GVHD) remains challenging because the unique cellular and molecular pathways that incite chronic GVHD are poorly understood. One major point of intervention for potential prevention of chronic GVHD occurs at the time of transplantation when acute donor anti-recipient immune responses first set the events in motion that result in chronic GVHD. After transplantation, additional insults causing tissue injury can incite aberrant immune responses and loss of tolerance, further contributing to chronic GVHD. Points of intervention are actively being identified so that chronic GVHD initiation pathways can be targeted without affecting immune function. The major objective in the field is to continue basic studies and to translate what is learned about etiopathology to develop targeted prevention strategies that decrease the risk of morbid chronic GVHD without increasing the risks of cancer relapse or infection. Development of strategies to predict the risk of developing debilitating or deadly chronic GVHD is a high research priority. This working group recommends further interrogation into the mechanisms underpinning chronic GVHD development, and we highlight considerations for future trial design in prevention trials.
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National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: IV. The 2020 Highly morbid forms report
Wolff, D., Radojcic, V., Lafyatis, R., Cinar, R., Rosenstein, R. K., Cowen, E. W., Cheng, G. S., Sheshadri, A., Bergeron, A., Williams, K. M., et al
Transplantation and cellular therapy. 2021
Abstract
Chronic graft-versus-host disease (GVHD) can be associated with significant morbidity, in part because of nonreversible fibrosis, which impacts physical functioning (eye, skin, lung manifestations) and mortality (lung, gastrointestinal manifestations). Progress in preventing severe morbidity and mortality associated with chronic GVHD is limited by a complex and incompletely understood disease biology and a lack of prognostic biomarkers. Likewise, treatment advances for highly morbid manifestations remain hindered by the absence of effective organ-specific approaches targeting "irreversible" fibrotic sequelae and difficulties in conducting clinical trials in a heterogeneous disease with small patient numbers. The purpose of this document is to identify current gaps, to outline a roadmap of research goals for highly morbid forms of chronic GVHD including advanced skin sclerosis, fasciitis, lung, ocular and gastrointestinal involvement, and to propose strategies for effective trial design. The working group made the following recommendations: (1) Phenotype chronic GVHD clinically and biologically in future cohorts, to describe the incidence, prognostic factors, mechanisms of organ damage, and clinical evolution of highly morbid conditions including long-term effects in children; (2) Conduct longitudinal multicenter studies with common definitions and research sample collections; (3) Develop new approaches for early identification and treatment of highly morbid forms of chronic GVHD, especially biologically targeted treatments, with a special focus on fibrotic changes; and (4) Establish primary endpoints for clinical trials addressing each highly morbid manifestation in relationship to the time point of intervention (early versus late). Alternative endpoints, such as lack of progression and improvement in physical functioning or quality of life, may be suitable for clinical trials in patients with highly morbid manifestations. Finally, new approaches for objective response assessment and exploration of novel trial designs for small populations are required.
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[Management of patients developing acute gastro-intestinal graft-versus-host-disease: Guidelines from the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)]
de Berranger, E., Charbonnier, A., Davy, E., Dendonker, C., Denis, V., Desmier, D., Farrugia, C., Guenounou, S., Guilbert, Y., Jost, E., et al
Bulletin du cancer. 2021
Abstract
Graft-versus-host disease (GVHD) is the most common complication after allogeneic hematopoietic cell transplantation (allo-HCT) with a frequency range of 30% to 50%. GVH is the leading cause of non-relapse-related deaths and a cause early mortality. Gastro-intestinal (GI) GVH results in digestive manifestations that involve the small intestine and the colon. The patient may then have diarrhea, intestinal bleeding, abdominal pain but also clinical signs such as nausea and vomiting may lead to anorexia. GI-GVHD promotes undernutrition as well as significant losses of vitamins and trace elements. In the case of post-transplant diarrhea, differential diagnosis can include GI-GVHD, infection and drug toxicity. Although, corticosteroids w/wo calcineurin inhibitors represent the standard of care in first line treatment, there is no consensus regarding salvage therapy in case of corticoresistant GI-GVH. In addition, assessment of early nutritional status would help combating undernutrition, which is an independent risk factor for mortality in patients with GI-GVHD. In this workshop of the Fancophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) we focused on the management of patients developing GI-GVHD following allo-HCT.
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7.
Brazilian Nutritional Consensus in Hematopoietic Stem Cell Transplantation: Graft- versus -host disease
Pereira, A. Z., Vigorito, A. C., Almeida, A. M., Candolo, A. A., Silva, A. C. L., Brandao-Anjos, A. E. P., Sa, B. L., Souza, C. L. S., Castro Junior, C. G., Oliveira, J. S. R., et al
Einstein (Sao Paulo, Brazil). 2020;18:eAE4799
Abstract
The Brazilian Consensus on Nutrition in Hematopoietic Stem Cell Transplantation: Graft- versus -host disease was approved by Sociedade Brasileira de Transplante de Medula Ossea , with the participation of 26 Brazilian hematopoietic stem cell transplantation centers. It describes the main nutritional protocols in cases of Graft- versus -host disease, the main complication of hematopoietic stem cell transplantation.
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8.
Extracorporeal photopheresis for graft versus host disease: A literature review and treatment guidelines proposed by the Nordic ECP Quality Group
Nygaard, M., Wichert, S., Berlin, G., Toss, F.
European journal of haematology. 2020
Abstract
Extracorporeal photopheresis (ECP) is one of the most used and established therapies for steroid-refractory graft versus host disease (GvHD), with a good effect to side effect profile. In this review we present a summary of present literature and provide evidence-based treatment guidelines for ECP in GvHD. The guidelines constitute a consensus statement formed by the Nordic ECP Quality Group representing all ECP centres in the Nordic countries, and aims to facilitate harmonization and evidence based practise. In developing the guidelines, we firstly conducted a thorough literature search of original articles and existing guidelines. In total, we identified 26 studies for ECP use in acute GvHD and 36 in chronic GvHD. The studies were generally small, retrospective and heterogeneous regarding patient characteristics, treatment schedule and outcome assessment. In general, a majority of patients achieved partial response or better, but response rates varied by the organs affected. Head to head comparisons to other treatment modalities were lacking. Overall, we consider the quality of evidence to be low-moderate (GRADE) and encourage future prospective multi-armed trials to strengthen the present recommendations. However, despite limitations in evidence strength, standardized treatment schedules and regular follow-up are imperative to ensure the best possible patient outcome.
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9.
NCCN Guidelines: Pretransplant Recipient Evaluation and Management of Graft-Versus-Host Disease
Cutler, C., Pavletic, S. Z.
Journal of the National Comprehensive Cancer Network : JNCCN. 2020;18(5):645-647
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10.
[Chinese consensus of allogeneic hematopoietic stem cell transplantation for hematological disease(III)-acute graft-versus-host disease (2020)]
Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi. 2020;41(7):E009