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EBMT 2021 Annual Meeting - Highlights from the Best Young Abstracts Awards

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This year, EBMT has given 10 special awards for the best abstracts submitted for oral presentations, and 5 special awards for the best abstracts submitted for poster presentations at this year’s online congress.

The prize-winning abstracts were selected from the top-scored abstracts submitted by young physicians (aged under 35 years).  Each awardee was presented with a € 500 prize during a dedicated awards session during yesterday’s online programme.

Sadly, there is not enough space in this article to highlight all our 15 winners, however here we meet two of them and find out more about their studies.

Simona Pagliuca

Immune escape driven by somatic mutations in class I/II HLA alleles in AML relapsing after allogenic HSCT:  a piece of the puzzle

To read Simona’s abstract, see: https://ebmt2021.abstractserver.com/program/#/details/presentations/1548

Q: Congratulations on receiving one of EBMT’s Best Young Abstract Awards Simona. Can you tell us a little about yourself, your age, institution and how long you have been involved in haematology research?

A: This award is a great honor for me, and I thank the scientific committee for such an appreciation of my work. I am 35; I am an Italian haematologist and mother of a toddler.

From a professional point of view, I grew up in Naples (Federico II University), where I received my MD and my residency in haematology, and where I started to open up my mind to the fascinating world of stem cell transplantation.  I later moved to Paris, and I spent more than three years as a transplant physician (within the role of “chef de clinic assistant”) in the Hematology and Transplant unit of Saint Louis Hospital. Then, I started a PhD program at the University of Paris in partnership with Cleveland Clinic (Cleveland, Ohio), where I am currently performing my research since November 2019.

Q: Why did you decide to do this study?

A:  Disease relapse remains one of the most fearsome complications in patients undergoing transplant for haematological disorders, and its treatment is rarely successful. For this reason, the full pathophysiological understanding of all the mechanisms involved is crucial. This study aims to investigate the role of HLA somatic mutations as one of the possible mechanisms of immune escape in acute myeloid leukemia relapsing after allogeneic stem cell transplantation. The idea is that pathogenic mutations targeting the highly polymorphic HLA loci may reduce the neoantigenic presentation on the surface of leukaemic blasts establishing the bases for an immune evasion from the graft versus leukaemia effect.

HLA loss is one of the most intriguing mechanisms of escape from anti-tumour surveillance established by neoplastic cells and may occur through several genetic or epigenetic modalities. Here we describe one of the possible genomic mode of HLA loss, representing, as said in the title of my abstract, only a piece of the puzzle of the pathophysiological scenario behind leukaemia relapse after transplant.

Q: What were the main findings?

A: We performed a comprehensive genomic study of almost 100 specimens sequentially collected from 48 patients with acute myeloid leukaemia relapsing after allogeneic transplant. We identified both in matched and mismatched settings, somatic mutations in class I and II HLA genes, prevalently at the moment of post-transplant relapse (samples at diagnosis and relapse after chemotherapy were also collected and analysed) and we found that those mutations were more likely associated with late relapses and with refractoriness to donor lymphocyte infusions. The findings behind this study shed light on the immunopathogenesis of post-transplant leukaemia relapse and may explain part of the ineffectiveness of post-transplant HLA-restricted immunomodulating strategies.

Q: What other projects are you working on at the moment?

A: Actually, this project belongs to a broader line of research that I am conducting at Cleveland Clinic and that seeks to investigate the germline and somatic genomic dysfunction of HLA machinery in several hematological disorders. Specifically, we are exploring the role of class I and II HLA somatic mutations in idiopathic bone marrow failures (another important context of haematological diseases exposed to strong immunological pressure). Importantly we are trying to define how the trajectories of this immunological escape relate within the clonal evolution scenario. Then we are studying the HLA structural variability in an evolutionary perspective, seeking to understand its role as immunogenetic determinant in the development of autoimmune disorders such as idiopathic aplastic anemia and in defining post-transplant outcomes in patients with malignant hematological diseases.

Note: Simona has also received a second award for another abstract she submitted: "HLA evolutionary divergence influences characteristics and outcomes of patients with aplastic anemia and paroxysmal nocturnal hemoglobinuria"

To read this second abstract, click here: https://ebmt2021.abstractserver.com/program/#/details/presentations/1596

Simona Pagliuca Best Young Abstract 2021


Nico Gagelmann

A prognostic score including mutation profile and clinical features for CMML undergoing stem cell transplantation

To read Nico’s abstract, see: https://ebmt2021.abstractserver.com/program/#/details/presentations/1590

Q: Congratulations on receiving one of EBMT’s Best Young Abstract Awards Nico. Can you tell us a little about yourself, your age, institution and how long you have been involved in haematology research?

A: I am Nico Gagelmann, 30 years old and a 1st year medical trainee, Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf.  I have been involved in the EBMT Chronic Malignancies Working Party from my 2nd year in medical school and since then continued to be involved in clinical research.

Q: Why did you decide to do this study?

A:  Chronic myelomonocytic leukaemia (CMML) is an understudied disease in the field of transplantation.  The main research is carried out in diagnosed patients in the nontransplant setting. Because the disease is relatively rare in transplant, we aimed to collaborate with as many centres as possible to gather clinical but, most importantly, also molecular-genetic information of the patients.

Q: What were the main findings?

A: We found that an ASXL1- and/or NRAS-mutated genotype, bone marrow blasts, and comorbidities independently predict survival in CMML after transplantation. These variables may build a CMML-transplant score predictive of survival and non-relapse mortality and may facilitate patient counselling. The calculator can be found under:
https://cmml-transplantscore.shinyapps.io/cmml-transplantscore/

Q: What other projects are you working on at the moment?

A: I continue to work on several questions across several diseases such as myelofibrosis, multiple myeloma, and acute leukemia, focusing on clinical questions that are still underrepresented.

Nico Gagelmann Best Young Abstract 2021

Thank you Simona and Nico! Congratulations on your award and prize.