-
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
-
-
-
Full text
-
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.
-
2.
Indications for haematopoietic cell transplantation for haematological diseases, solid tumours and immune disorders: current practice in Europe, 2022
Snowden, J. A., Sánchez-Ortega, I., Corbacioglu, S., Basak, G. W., Chabannon, C., de la Camara, R., Dolstra, H., Duarte, R. F., Glass, B., Greco, R., et al
Bone marrow transplantation. 2022;:1-23
-
-
-
Free full text
-
Full text
-
Editor's Choice
Abstract
For over two decades, the EBMT has updated recommendations on indications for haematopoietic cell transplantation (HCT) practice based on clinical and scientific developments in the field. This is the eighth special EBMT report on the indications for HCT for haematological diseases, solid tumours and immune disorders. Our aim is to provide general guidance on HCT indications according to prevailing clinical practice in EBMT countries and centres. In order to inform patient decisions, these recommendations must be considered in conjunction with the risk of the disease, risk of HCT procedure and non-transplant strategies, including evolving cellular therapies. HCT techniques are constantly evolving and we make no specific recommendations, but encourage harmonisation of practice, where possible, to ensure experience across indications can be meaningfully aggregated via registry outputs. We also recommend working according to JACIE accreditation standards to maintain quality in clinical and laboratory components of practice, including benchmarking of survival outcomes. Since the last edition, the COVID-19 pandemic has affected clinical decision making and activity across indications. Although the full impact of the pandemic is yet to be determined, we recommend that decision making across indications is delivered with ongoing reference to EBMT and national COVID-19 guidance, in accordance with current local conditions.
PICO Summary
Population
Patients with haematological diseases, solid tumours and immune disorders
Intervention
Updated recommendations on indications for haematopoietic cell transplantation, according to prevailing clinical practice in EBMT countries and centres
Comparison
None
Outcome
Although the full impact of the pandemic is yet to be determined, we recommend that decision making across indications is delivered with ongoing reference to EBMT and national COVID-19 guidance, in accordance with current local conditions.
-
3.
Harmonizing Definitions for Diagnostic Criteria and Prognostic Assessment of Transplant Associated Thrombotic Microangiopathy: A Report on Behalf of the European Society for Blood and Marrow Transplantation (EBMT), American Society for Transplantation and Cellular Therapy (ASTCT), Asia-Pacific Blood and Marrow Transplantation Group (APBMT) and the Center for International Blood and Marrow Transplant Research (CIBMTR)
Schoettler, M., Carreras, E., Cho, B., Dandoy, C. E., Ho, V. T., Jodele, S., Moissev, I., Sanchez-Ortega, I., Srivastava, A., Atsuta, Y., et al
Transplantation and cellular therapy. 2022
Abstract
BACKGROUND/RATIONALE Transplant-associated thrombotic microangiopathy (TA-TMA) is an increasingly recognized complication of hematopoietic cell transplant (HCT) associated with significant morbidity and mortality. However, TA-TMA is a clinical diagnosis and multiple criteria are proposed without universal application. While some patients have a self-resolving disease, others progress to multi-organ failure and/or death. Poor prognostic features are also not uniformly accepted. The lack of harmonization of diagnostic and prognostic markers have precluded multi-institutional studies to better understand incidence and outcomes. Even current interventional trials use different criteria, making it challenging to interpret the data. To address this urgent need, the American Society for Transplantation and Cellular Therapy, Center for International Bone Marrow Transplant Research, Asia-Pacific Blood and Marrow Transplantation, and European Society for Blood and Marrow Transplantation nominated representatives, forming an expert panel to come to a consensus on diagnostic and prognostic criteria. METHODS The panel reviewed literature, generated consensus statements using the Delphi Method regarding diagnostic and prognostic features of TA-TMA, and identified future directions of investigation. SUMMARY OF CONSENSUS STATEMENTS Consensus was reached on four key concepts. 1) TA-TMA can be diagnosed using clinical and laboratory criteria or tissue biopsy of kidney or gastrointestinal tissue. However, a biopsy is not required. 2) Consensus diagnostic criteria are proposed using modified Jodele criteria with additional definitions of anemia and thrombocytopenia. TA-TMA is diagnosed when ≥ 4/7 following features occur twice within 14 days: anemia, defined as failure to achieve transfusion independence despite neutrophil engraftment, hemoglobin decline by ≥1 gm/dL, or new onset transfusion dependence, thrombocytopenia defined as failure to achieve platelet engraftment, higher than expected transfusion needs, refractory to platelet transfusions, or ≥ 50% reduction in baseline platelet count after full platelet engraftment, lactate dehydrogenase (LDH) >ULN, schistocytes, hypertension, sC5b-9>ULN and proteinuria (≥ 1mg/mg random urine protein creatinine ratio, rUPCR). 3) Patients with any of the following features have an increased risk of non-relapse mortality and should be stratified as high-risk TA-TMA: elevated sC5b-9, LDH ≥2X ULN, rUPCR ≥1 mg/mg, multiorgan dysfunction, concurrent grade II-IV acute graft versus host disease, or infection (bacterial or viral). 4) All allogeneic and pediatric autologous HCT recipients with neuroblastoma should be screened weekly for TA-TMA during the first 100 days post-HCT. If patients are diagnosed with TA-TMA, they should be risk stratified. Patients with high-risk disease should be offered participation in a clinical trial for TA-TMA-directed therapy if available. FUTURE DIRECTIONS We propose that these criteria and risk stratification features be used in data registries, prospective studies, and clinical practice across international settings. This harmonization will facilitate the investigation of TA-TMA across populations diverse in race, ethnicity, age, disease indication, and transplant characteristics. As these criteria are broadly utilized, we expect continued refinement as necessary. Efforts to identify more specific diagnostic and prognostic biomarkers are a top priority of the field. Lastly, an investigation of the impact of TA-TMA-directed treatment, particularly in the setting of concurrent highly morbid complications such as steroid-refractory GVHD and infection, is critically needed.
-
4.
Worldwide Network for Blood and Marrow Transplantation (WBMT) Recommendations Regarding Essential Medications Required To Establish An Early Stage Hematopoietic Cell Transplantation Program
El Fakih, R., Greinix, H., Koh, M., Shaw, B., Mohty, M., Al Nahedh, M., Saber, W., Kharfan-Dabaja, M. A., Perales, M. A., Savani, B. N., et al
Transplantation and cellular therapy. 2021;27(3):267.e1-267.e5
Abstract
Establishing a hematopoietic cell transplantation (HCT) program is complex. Planning is essential while establishing such a program to overcome the expected challenges. Authorities involved in HCT program establishment will need to coordinate the efforts between the different departments required to start up the program. One essential department is pharmacy and the medications required. To help facilitate this, the Worldwide Network for Blood and Marrow Transplantation organized a structured survey to address the essential medications required to start up an HCT program. A group of senior physicians and pharmacists prepared a list of the medications used at the different phases of transplantation. These drugs were then rated by a questionnaire using a scale of necessity based on the stage of development of the transplant program. The questionnaire was sent to 30 physicians, in different parts of the world, who have between 5 and 40 years of experience in autologous and/or allogeneic transplantation. This group of experts scored each medication on a 7-point scale, ranging from an absolute requirement (score of 1) to not required (score of 7). The results are presented here to help guide the prioritization of required medications.
-
5.
ASTCT, CIBMTR, and EBMT clinical practice recommendations for transplant and cellular therapies in mantle cell lymphoma
Munshi, P. N., Hamadani, M., Kumar, A., Dreger, P., Friedberg, J. W., Dreyling, M., Kahl, B., Jerkeman, M., Kharfan-Dabaja, M. A., Locke, F. L., et al
Bone marrow transplantation. 2021
Abstract
Autologous (auto-) or allogeneic (allo-) hematopoietic cell transplantation (HCT) are accepted treatment modalities for mantle cell lymphoma (MCL). Recently, chimeric antigen receptor (CAR) T-cell therapy received approval for MCL; however, its exact place and sequence in relation to HCT is unclear. The ASTCT, CIBMTR, and the EBMT, jointly convened an expert panel to formulate consensus recommendations for role, timing, and sequencing of auto-, allo-HCT, and CAR T-cell therapy for patients with newly diagnosed and relapsed/refractory (R/R) MCL. The RAND-modified Delphi method was used to generate consensus statements. Seventeen consensus statements were generated; in the first-line setting auto-HCT consolidation represents standard-of-care in eligible patients, whereas there is no clear role of allo-HCT or CAR T-cell therapy, outside of a clinical trial. In the R/R setting, the preferential option is CAR T-cell therapy especially in MCL failing or intolerant to at least one Bruton's tyrosine kinase inhibitor, while allo-HCT is recommended if CAR T-cell therapy has failed or is not feasible. In the absence of contemporary evidence-based data, the panel found RAND-modified Delphi methodology effective in providing a formal framework for developing consensus recommendations for the timing and sequence of cellular therapies for MCL.
-
6.
Maintenance Therapies for Hodgkin and Non-Hodgkin Lymphomas After Autologous Transplantation: A Consensus Project of ASBMT, CIBMTR, and the Lymphoma Working Party of EBMT
Kanate, A. S., Kumar, A., Dreger, P., Dreyling, M., Le Gouill, S., Corradini, P., Bredeson, C., Fenske, T. S., Smith, S. M., Sureda, A., et al
JAMA oncology. 2019
-
-
Free full text
-
Abstract
Importance: Maintenance therapies are often considered as a therapeutic strategy in patients with lymphoma following autologous hematopoietic cell transplantation (auto-HCT) to mitigate the risk of disease relapse. With an evolving therapeutic landscape, where novel drugs are moving earlier in therapy lines, evidence relevant to contemporary practice is increasingly limited. The American Society for Blood and Marrow Transplantation (ASBMT), Center for International Blood and Marrow Transplant Research (CIBMTR), and European Society for Blood and Marrow Transplantation (EBMT) jointly convened an expert panel with diverse expertise and geographical representation to formulate consensus recommendations regarding the use of maintenance and/or consolidation therapies after auto-HCT in patients with lymphoma. Observations: The RAND-modified Delphi method was used to generate consensus statements where at least 75% vote in favor of a recommendation was considered as consensus. The process included 3 online surveys moderated by an independent methodological expert to ensure anonymity and an in-person meeting. The panel recommended restricting the histologic categories covered in this project to Hodgkin lymphoma (HL), mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), and follicular lymphoma. On completion of the voting process, the panel generated 22 consensus statements regarding post auto-HCT maintenance and/or consolidation therapies. The grade A recommendations included endorsement of: (1) brentuximab vedotin (BV) maintenance and/or consolidation in BV-naive high-risk HL, (2) rituximab maintenance in MCL undergoing auto-HCT after first-line therapy, (3) rituximab maintenance in rituximab-naive FL, and (4) No post auto-HCT maintenance was recommended in DLBCL. The panel also developed consensus statements for important real-world clinical scenarios, where randomized data are lacking to guide clinical practice. Conclusions and Relevance: In the absence of contemporary evidence-based data, the panel found RAND-modified Delphi methodology effective in providing a rigorous framework for developing consensus recommendations for post auto-HCT maintenance and/or consolidation therapies in lymphoma.
-
7.
Agreements and uncertainties in autologous haematopoietic stem cell mobilization and collection. A Spanish consensus document
Bueno, J. L., Alegre, A., Lopez-Villar, O., Querol, S., Arroyo, J. L., Goterris, R., Sureda, A., Garcia-Gala, J. M., Amunarriz, C., Albo, C., et al
Bone marrow transplantation. 2019
Abstract
Although many experts position statements on autologous stem cell mobilization have been published, there are some aspects that are still under discussion. A Spanish Hematologist expert group was summoned to settle on agreements and uncertainties on PBSCs mobilization, including factors not always considered; as apheresis and cytometry key factors that determine a successful PBSC collection. This document reviews critical factors that define poor mobilizer patients and the tools to better collect the desired stem cells for a successful autologous haematopoietic stem cell transplant.
-
8.
Recommendations from the European Society for Blood and Marrow Transplantation (EBMT) for a curriculum in hematopoietic cell transplantation
Mohty, M., Duarte, R. F., Kuball, J., Bader, P., Basak, G. W., Bonini, C., Carreras, E., Chabannon, C., Dufour, C., Gennery, A., et al
Bone marrow transplantation. 2018
Abstract
Hematopoietic cell transplantation (HCT) is increasingly used worldwide. This treatment approach is complex and requires specific knowledge and training. The European Society for Blood and Marrow Transplantation (EBMT) identified the need for a set of international recommendations for the clinical training of physicians to qualify them as being competent in performing HCT procedures as well as novel cellular immune therapies and taking care of such patients. The goal is to implement an EBMT HCT-focused global curriculum (EBMT-GC) that can serve as a tool for the development of the HCT sub-specialty worldwide. Despite the diversity and heterogeneity of health and educational systems around the globe, this set of recommendations can be fairly adopted by any national educational and health authorities and can be adjusted to specific conditions and resources of a given country, if needed. The ultimate goal of the EBMT-GC is to define standards for personal knowledge in allogeneic stem cell transplantation for physicians worldwide in order to ensure that all patients will receive treatment by well-trained physicians.
-
9.
The EBMT-ELN working group recommendations on the prophylaxis and treatment of GvHD: a change-control analysis
Ruutu, T., Gratwohl, A., Niederwieser, D., de Witte, T., van der Werf, S., van Biezen, A., Mohty, M., Kroger, N., Rambaldi, A., McGrath, E., et al
Bone Marrow Transplantation. 2017;52(3):357-362
Abstract
In 2013, recommendations for a standardized practice in the prophylaxis and treatment of GvHD were adopted and published by the European Society for Blood and Marrow Transplantation and the European LeukemiaNet. One year later, all 341 European Society for Blood and Marrow Transplantation centres performing allogeneic haematopoietic stem cell transplantation were contacted for a change-control analysis and asked to fill in a questionnaire; 111 centres (33%) responded. Of these, 83% had been aware of the recommendations. Paediatric centres (P=0.004), centres with shorter programme duration (P=0.049), not JACIE (the Joint Accreditation Committee of the International Society for Cellular Therapy and the European Society for Blood and Marrow Transplantation)-accredited centres (P=0.010) and centres from middle-income countries (P=0.033) were more likely to be unaware of the recommendations. Thirty-eight per cent of the centres regarded the recommendations as relevant guidelines affecting their policies, 61% as interesting information. Thirty per cent had decided to make changes in their institutional protocols based on the recommendations. More than 80% were willing to use the recommendations for a control arm in randomized studies. This survey shows that the published recommendations had some, though insufficient, impact on the strategies and methods of allogeneic haematopoietic stem cell transplantation applied by the centres. It also identified some of the weaknesses to be addressed when releasing recommendations in the future.
-
10.
[Mobilization of peripheral blood stem cells with plerixafor in poor mobilizer patients]. [Spanish]
Sancho, J. M., Duarte, R., Medina, L., Querol, S., Marin, P., Sureda, A., en representacion del Grupo de Trabajo de Movilizacion de la Sociedad Catalana de Hematologia y Hemoterapia y de la Sociedad Catalano-Balear de Transfusion, Sanguinea
Medicina Clinica. 2016;147(5):223.e1-7
Abstract
BACKGROUND AND OBJECTIVE Poor mobilization of peripheral blood stem cells (CD34(+) cells) from bone marrow is a frequent reason for not reaching the autologous stem cell trasplantation (SCT) procedure in patients diagnosed with lymphoma or myeloma. Plerixafor, a reversible inhibitor of the binding of stromal cell-derived factor 1 to its cognate receptor CXCR4, has demonstrated a higher capacity for the mobilization of peripheral blood stem cells in combination with granulocyte colony stimulating factor (G-CSF) compared with G-CSF alone. For this reason, plerixafor is now indicated for poor mobilizer myeloma or lymphoma patients. Some studies have recently indicated that a pre-emptive strategy of plerixafor use during first mobilization, according to the number of CD34(+) mobilized cells in peripheral blood or to the harvested CD34(+) cells after first apheresis, could avoid mobilization failures and re-mobilizations, as well as the delay of autologous SCT. The aim of this consensus was to perform a review of published studies on pre-emptive strategy and to establish common recommendations for hospitals in Catalonia and Balearics on the use of pre-emptive plerixafor. METHODS For the Consensus, physicians from participant hospitals met to review previous studies as well as previous own data about plerixafor use. The GRADE system was used to qualify the available evidence and to establish recommendations on the use of pre-emptive plerixafor. RESULTS AND CONCLUSIONS After a review of the literature, the expert consensus recommended the administration of pre-emptive plerixafor for multiple myeloma or lymphoma patients with a CD34+ cell count lower than 10 cells/muL in peripheral blood (measured in the morning of day 4 of mobilization with G-CSF or after haematopietic recovery in the case of mobilization with chemotherapy plus G-CSF). Copyright © 2016 Elsevier Espana, S.L.U. All rights reserved.