Authors
Maria Gabarros-Subira, Helena Pomares, Francisco Beas, Sara Torres-Esquius, Miguel López-Esteban, Alberto Hernández-Sánchez, Elisa Lopez-Fernandez, Guillermo Ramil, Lourdes Hermosín, Gonzalo Carreño-Tarragona, Valle Gomez-Garcia de Soria, Iván Martín, Juan Jose Dominguez-Garcia, Marta Santiago, María Jesús Pascual-Cascón, Marina Díaz-Beyá, Guiomar Bautista, Tzu-Hua Chen-Liang, Francisco Ortuño Giner, Georgina Gener-Ricos, Laura Palomo, Lucia Garcia-Maño, María Teresa Gómez Casares, Cristina Bilbao-Sieyro, Ana Alfonso-Pierola, Miguel Piris-Villaespesa, Nuria Revilla, Sara Alonso-Alvarez, Ana Iborra, Blanca Ferrer-Lores, Lucia López-Corral, Marta Pratcorona, Pascual Balsalobre, Ferran Balbastre-Úbeda, Guillermo Orti, Alberto Mussetti, Rosa Ayala, Ismael Buno, José Cervera, María Díez-Campelo, Ana Río-Machín, Maria Julia Montoro, Lurdes Zamora, Mar Tormo, Francesc Bosch, Francisca Hernández Mohedo, Montserrat Arnan, David Valcarcel, Carolina Martinez-Laperche, Andrés Jerez
Published in
Blood. Oct 26, 2026. Epub Oct 26, 2026.
Abstract
Donor cell-derived hematologic neoplasm (DDHN) is defined as a de novo hematologic malignancy originated from transplanted donor stem cells, distinct from the original recipient's disease (ORD). Its prevalence and biological mechanisms remain poorly defined. We conducted a nationwide study to estimate the prevalence of DDHN and characterize its clinical and molecular features. Twenty-four transplantation centers systematically reviewed their allogeneic hematopoietic stem cell transplantation (allo-HSCT) cohorts. DDHN diagnosis required cytogenetic or molecular donor-origin confirmation. Molecular studies included germline-augmented targeted NGS, whole-exome sequencing, and donor-recipient comparative analyses. We identified 39 DDHN cases diagnosed between 2007 and 2025. Among 8,465 allo-HSCT performed between 2013-2022, DDHN prevalence was 0.28%, with a marked predominance after related-donor compared with unrelated transplantation (0.41% vs. 0.06%, p=0.0026). Median latency from transplantation to DDHN diagnosis was 56 months. Most DDHN were myeloid neoplasms, predominantly myelodysplastic neoplasms (51%) and acute myeloid leukemia (36%). Molecular characterization, available in 33 cases, revealed germline predisposition as the predominant underlying mechanism. Pathogenic/likely pathogenic germline variants were identified in 10 cases, involving DDX41 (n=7), CEBPA (n=2), and CHEK2 (n=1), all after a related-donor transplantation. DDX41-associated DDHN showed recurrent somatic hits and low genomic complexity. Donor-derived clonal hematopoiesis was confirmed in only one myeloid case involving U2AF1. These findings support inherited germline predisposition as the potential main molecular driver of DDHN after related allo-HSCT, reinforcing the recommendation for comprehensive germline evaluation of patients at ORD diagnosis prior to transplantation, followed by targeted cascade screening of candidate related donors.
PMID:
42932250
Bibliographic data and abstract were imported from PubMed on 27 Oct 2026.
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