EBMT NEWSLETTER | September 2016 | Volume 53 - Issue 4

EBMT
Important dates
The impact of HLA-matching on reduced intensity conditioning regimen unrelated donor allogeneic stem cell transplantation for acute myeloid leukemia in patients above 50 years – a report from the EBMT acute leukemia working party. Rubio MT, Savani BN, Labopin M, Polge E, Niederwieser D, Ganser A, Schwerdtfeger R, Ehninger G, Finke J, Renate A, Craddock C, Kröger N, Hallek M, Jindra P, Mohty M, Nagler A. J Hematol Oncol. 2016 Aug 3;9(1):65. doi: 10.1186/s13045-016-0295-9.
 
As discussed in our previous newsletter, the Acute Leukemia Working Party (ALWP) has recently shown that in the context of HLA-mismatched HCT from unrelated donors, reduced-intensity conditioning regimens are superior to myeloablative regimens in patients with acute myeloid leukemia 50 years of age and older, and make allogeneic HCT feasible in this setting. Now, a new retrospective analysis from the ALWP in a large group of 3398 patients above 50 years of age with acute myeloid leukemia, studies the impact of HLA-matching on unrelated donor HCT outcome (10/10: 2567, 9/10: 723, 8/10: 108).  Compared to 10/10 M-URD, patients transplanted in the first complete remission (CR1) with a 9 or an 8/10 mM-URD had decreased 2-year leukemia free (p = 0.005) and overall survivals (56.7, 46.1, and 50.2 %, respectively, p = 0.005), while outcomes were comparable regardless of the level of HLA-matching for patients transplanted beyond CR1. In multivariate analysis, 9/10 versus 10/10 URD was associated with higher non-relapse mortality (HR 1.34, p = 0.001), similar risk of relapse and chronic GVHD and inferior LFS (HR 1.25, p = 0.0001), and OS (HR 1.27, p = 0.0001). In spite of reduced intensity conditioning regimens making allogeneic HCT from mismatched unrelated donors feasible for patients with acute myeloid leukemia above the age of 50, a 10/10 matched donor remains the preferable option for these patients. Thus, the use of a 9/10 or an 8/10 mismatched donors in patients not having a fully matched donor represents an alternative therapeutic option that should be compared to other emerging alternative donor transplant strategies.

Management of Epstein-Barr Virus infections and post-transplant lymphoproliferative disorders in patients after allogeneic hematopoietic stem cell transplantation: Sixth European Conference on Infections in Leukemia (ECIL-6) guidelines. Styczynski J, van der Velden W, Fox CP, Engelhard D, de la Camara R, Cordonnier C, Ljungman P; Sixth European Conference on Infections in Leukemia, a joint venture of the Infectious Diseases Working Party of the European Society of Blood and Marrow Transplantation (EBMT-IDWP), the Infectious Diseases Group of the European Organization for Research and Treatment of Cancer (EORTC-IDG), the International Immunocompromised Host Society (ICHS) and the European Leukemia Net (ELN). Haematologica. 2016 Jul;101(7):803-11. doi: 10.3324/haematol.2016.144428.
 
The sixth European Conference on Infections in Leukemia (ECIL), with participation of the EBMT Infectious Diseases Working Party, has recently published un update on the management of Epstein-Barr Virus (EBV) infections and post-transplant lymphoproliferative disorders (PTLD) in recipients of allogeneic HCT. A first set of recommendations for management of EBV infections in allogeneic HCT was released following the second ECIL in 2007. Much has changed since then, and more recently, guidelines on EBV infections and PTLD after solid-organ transplants have been produced. This paper now presents updated recommendations for EBV infections and PTLD following allogeneic HCT based on the analysis of recent data. They cover recommendations for prevention, for diagnosis and monitoring of EBV DNA-emia, for definition and diagnosis of EBV-diseases including PTLD, and for the various therapeutic strategies, including preemptive therapy against EBV disease and PTLD as well as treatment of the established disease. They give special consideration to EBV-PTLD affecting the central nervous system. Overall, rituximab, reduction of immunosuppression and EBV-specific cytotoxic T-cell therapy are recommended as first-line therapy, whilst unselected donor lymphocyte infusions or chemotherapy are options for second-line therapy. Other methods, including antiviral drugs are discouraged. Finally, a number of possible future developments are discussed, including obinutuzumab and new anti-CD20 monoclonal antibodies, brentuximab vedotin and anti-CD30 monoclonal antibodies, and new antivirals (i.e. Brincidofovir; currently unlicensed) with excellent antiviral activity against EBV in vitro.

Outcomes of unrelated cord blood transplantation in patients with multiple myeloma: a survey on behalf of Eurocord, the Cord Blood Committee of the Cellular Therapy and Immunobiology Working Party and the Chronic Malignancy Working Party of the EBMT. Paviglianiti A, Xavier E, Ruggeri A, Ceballos P, Deconinck E, Cornelissen JJ, Nguyen-Quoc S, Maillard N, Sanz G, Rohrlich PS, Garderet L, Volt F, Rocha V, Kroeger N, Gluckman E, Fegueux N, Mohty M. Haematologica. 2016 Sep;101(9):1120-7. doi: 10.3324/haematol.2015.138917. Epub 2016 May 26.
 
In our previous EBMT newsletter, we reviewed an important study by the Chronic Malignancies Working Party (CMWP) looking at trends and outcomes over 25 years of allogeneic HCT in multiple myeloma. The study showed that although its role and positioning in treatment algorithms are not well defined, there has been a clear increase in activity, and an unmet need for further research in this field. Here, we present a recent study also by the CMWP, in collaboration with Eurocord and the Cord Blood Committee of the EBMT Cellular Therapy and Immunobiology Working Party, reporting a relatively large series of 95 recipients of cord blood allogeneic HCT for multiple myeloma or plasma cell leukemia. Although the place of cord blood HCT in multiple myeloma remains unclear, this study provides important feasibility data to our understanding of allogeneic HCT in myeloma patients. With a 41-month median follow up, the estimated non-relapse mortality was 29%, relapse rate 47%, progression-free survival 24% and overall survival 40% at 3 years. Although the majority of patients received reduced-intensity conditioning regimens (82%), those with myeloablative conditioning regimens had higher non-relapse mortality and poorer overall survival. In addition, the use of ATG in 24% of cases, had an independent negative impact on non-relapse mortality and overall survival. Finally, patients with high cytogenetic risk had higher relapse and worse progression-free and overall survival. Overall, the study suggests that unrelated cord blood HCT is feasible in patients with multiple myeloma, and that high-risk cytogenetics and the use of ATG are independently associated with worse survival.

Development, preliminary usability and accuracy testing of the EBMT 'eGVHD App' to support GvHD assessment according to NIH criteria – a proof of concept. Schoemans H, Goris K, Durm RV, Vanhoof J, Wolff D, Greinix H, Pavletic S, Lee SJ, Maertens J, Geest SD, Dobbels F, Duarte RF. Bone Marrow Transplant. 2016 Aug;51(8):1062-5. doi: 10.1038/bmt.2016.26. Epub 2016 Apr 4.
 
The recently updated NIH criteria for chronic GvHD have consolidated the standardization of diagnosis and scoring of GvHD through an international effort. The use of these criteria should be a priority for clinical practice. In addition, it is a priority for clinical research. Since all GvHD registry data rely on centers’ self-reporting, an accurate diagnosis and score through the NIH criteria would be of paramount importance to correctly evaluate transplant outcomes. Unfortunately, the dissemination and implementation of NIH GvHD criteria is often considered challenging by clinicians, due to perceived complexity and time investment issues, limiting their use in daily clinical practice. The EBMT Complications and Quality of Life Working Party (CQLWP), in collaboration with an international task-force, had recently identified barriers to the dissemination and implementation of chronic GVHD NIH criteria into clinical practice. Now, in collaboration with the University Hospital of Leuven in Belgium, the CQLWP has developed a computer-/web-based algorithm-driven application, the EBMT ‘eGVHD App’, to help clinicians diagnose and score the severity of GvHD faster and more accurately. This manuscript describes the initial development, preliminary usability and accuracy testing of the EBMT ‘eGVHD App’. The results show that the App is not only user friendly and intuitive, but also increases GVHD diagnostic and scoring accuracy. Subsequent validation of the electronic decision algorithm and larger-scale testing and implementation are currently underway. The ‘eGVHD App’ is a first model of such a computer-/web-based application for our Society. Further development and application of this technology to the dissemination and implementation of other key topics of HCT is warranted, as tools to improve clinical practice and research in our field.
 

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Bone Marrow Transplantation publishes high quality, peer reviewed original research and reviews that address all aspects of basic biology and clinical use of haemopoietic cell transplantation.
The journal also covers all aspects of the research and treatment of transplant-related complications and consequences including quality of life and psychological issues. Basic research studies on topics of relevance are also covered.
 

2015 Impact Factor 3.636*
*2015 Journal Citation Reports® Science Edition (Thomson Reuters, 2016)
 
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Development, preliminary usability and accuracy testing of the EBMT ‘eGVHD App’ to support GvHD assessment according to NIH criteria—a proof of concept
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The bone marrow microenvironment is similarly impaired in allogeneic hematopoietic stem cell transplantation patients with early and late poor graft function
Y Kong, Y-T Wang et al
 
Does ex vivo CD34+ positive selection influence outcome after autologous hematopoietic stem cell transplantation in systemic sclerosis patients?
M C Oliveira, M Labopin et al
 
Improvement of overall survival after allogeneic hematopoietic stem cell transplantation for children and adolescents: a three-decade experience of a single institution
E Brissot, F Rialland et al
 
A randomized phase II study of stem cell mobilization with cyclophosphamide+G-CSF or G-CSF alone after lenalidomide-based induction in multiple myeloma
R Silvennoinen, P Anttila et al
 
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