Suspected Donor-derived Myeloid Neoplasia After Allogeneic HSCT: A Case-based Review of Clonal Evolution

Background/Aim: Donor-derived leukemia represents a rare but increasingly recognized clinical complication of allogeneic hematopoietic stem cell transplantation. Emerging evidence indicates that clonal hematopoiesis of indeterminate potential in donors provides the biological substrate for donor-derived leukemia, while post-transplant immune pressure and niche damage drive clonal selection and leukemic evolution. Case Report: We describe the case of a 70-year-old woman with acute myeloid leukemia who underwent matched unrelated donor allogeneic hematopoietic stem cell transplantation (allo-HSCT) from a 25-year-old female donor. Following transplantation, serial bone marrow examinations demonstrated persistent predominant donor chimerism accompanied by progressive expansion of an aberrant myeloid population, increasing from approximately 2% to 14% by multiparametric flow cytometry, without clear morphologic relapse. Targeted next-generation sequencing at hematologic progression identified a pathogenic RAS-pathway mutation with a variant allele frequency of 7%, while no molecular features overlapping with the initially characterized acute myelogenous leukemia (AML) were identified. However, pre-transplant next-generation sequencing (NGS) data from both donor and recipient and lineage-specific chimerism of the abnormal population were unavailable, preventing definitive demonstration of donor origin. Conclusion: This case represents a suspected donor-derived myeloid neoplasm arising after allo-HSCT and illustrates the diagnostic difficulty of distinguishing donor-derived disease from relapse and other post-transplant myeloid neoplasms. The case also highlights the potential value of integrating serial flow cytometry, molecular profiling, and lineage-specific chimerism analyses when unexplained cytopenias or progressive abnormal myeloid populations develop despite preserved donor chimerism. The proposed evolutionary and microenvironmental mechanisms should be considered hypothesis-generating and require further validation in molecularly characterized cases.