Molecular Underpinnings and Prevalence of Donor Cell-Derived Hematologic Neoplasms among Spanish Transplantation Centers.

DDX41, CEBPA, CHEK2

Germline predisposition transferred with the graft from a related donor: pathogenic or likely pathogenic variants in DDX41 (7 cases), CEBPA (2) and CHEK2 (1)

This nationwide study across 24 Spanish centres estimated the prevalence of donor cell-derived hematologic neoplasms (DDHN, a de novo hematologic malignancy arising from transplanted donor stem cells, distinct from the recipient's original disease) after allogeneic hematopoietic stem cell transplantation. Thirty-nine cases were identified between 2007 and 2025; among 8,465 transplants performed in 2013-2022, prevalence was 0.28%, markedly higher after related-donor than after unrelated-donor transplantation (0.41% vs 0.06%, p=0.0026). Most were myeloid neoplasms, mainly myelodysplastic neoplasms (51%) and acute myeloid leukemia (36%), diagnosed after a median latency of 56 months. Among 33 characterised cases, a pathogenic or likely pathogenic germline variant was found in 10, all after related-donor transplantation: DDX41 (n=7), CEBPA (n=2) and CHEK2 (n=1). Donor-derived clonal hematopoiesis was confirmed in only one case (U2AF1), and the authors recommend comprehensive germline evaluation of the recipient at initial diagnosis, before transplantation, followed by targeted cascade screening of candidate related donors.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

The clinical message is clear: when the recipient carries a germline predisposition, a related donor may share it, and transplantation then transfers the risk with the graft. With 10 carriers the sample remains small, but the predominance of DDX41 and the restriction of germline cases to related-donor transplants are consistent. The study strengthens the case for systematic germline testing of myeloid neoplasms considered for allogeneic transplantation, echoing last week's study on DDX41 and transplantation.

Analysis by Dr Thibaut Benquey