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EBMT 2026 | The EBMT best practice guidelines for donor-derived myeloid neoplasms
Carmelo Gurnari, MD, University of Rome Tor Vergata, Rome, Italy, and Cleveland Clinic, Cleveland, OH, highlights the importance of identifying germline predisposition in stem cell transplant donors to prevent donor-derived myeloid neoplasms, highlighting that approximately 80% of donor cell leukemias are due to inherited mutations in the donor that are passed on through the graft. Dr Gurnari discusses the EBMT best-practice guidelines for managing donor cell leukemias, which will be published in due course. This interview took place at the 52nd Annual Meeting of the EBMT in Madrid, Spain.
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Transcript
The presence of germline predisposition is important because sometimes what happened in the past when we didn’t know that these germline mutations might be present or we were not able to identify them because of the limits of molecular tools in the past decades, we were witnessing a particular case of leukemia or relapse after transplant which is called donor cell leukemia...
The presence of germline predisposition is important because sometimes what happened in the past when we didn’t know that these germline mutations might be present or we were not able to identify them because of the limits of molecular tools in the past decades, we were witnessing a particular case of leukemia or relapse after transplant which is called donor cell leukemia. This is only two to five percent of all relapses after allogeneic transplant, but about eighty percent of the time this is probably due to the presence of a germline mutation that inadvertently is passed along with the graft. Now that we are able to identify this mutation, we know that the majority are those genes that perhaps have not extra-hematological phenotypes and therefore are difficult to identify in donors if you don’t know anything about the family history of the donor or you didn’t identify this with the molecular tools.
Therefore we, together with the chronic malignancy working party of the EBMT, in one of the efforts of the harmonization guidelines, tried to tackle this problem after a meeting in Berlin where we gathered together. We decided to address what we can do for the best clinical management of donor cell leukemias and these guidelines are soon to be published in the Lancet Haematology, and today we have the session where we will discuss how to best diagnose and approach these patients. It’s imperative when we have a donor cell leukemia to assess the molecular profile of this patient because sometimes not only is it important to understand if there’s a germline predisposition and therefore go back to the donor, if it’s a relative or especially if it’s like an unrelated donor, to understand if we can reach out to the donor himself or herself. But also to understand if there are molecular targets that we can use for the donor cell leukemia that we have in front of us and perhaps bridge the patient to another second allogeneic transplant, which in most cases is the only curative option for these patients. But it is obviously tricky because these patients are have already been allografted and therefore a second allograft is decided upon a specific indications like age, the performance status of the patient, the previous iatrogenic burden and chemotherapy exposure. So a lot of factors go into that decision.
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