Allogeneic Stem Cell Transplantation in Patients With Mixed Chimerism Following Double Cord Blood Transplantation: A Case Report

Introduction Double‐unit cord blood transplantation (dCBT) is an established strategy to enhance progenitor cell dose and accelerate hematopoietic recovery when a matched sibling or unrelated donor is unavailable. While dCBT typically results in the dominance of a single unit, the persistence of donor–donor mixed chimerism is an exceptionally rare clinical phenomenon. This case report describes a unique therapeutic strategy where persistent donor–donor chimerism following dCBT was utilized to redefine the recipient’s HLA profile for a subsequent successful allogeneic transplantation. Case Presentation A 38‐year‐old patient with diffuse large B‐cell lymphoma experienced disease relapse following autologous peripheral blood stem cell transplantation. After achieving a second remission through salvage chemotherapy, the patient underwent dCBT due to the absence of a compatible HLA‐matched donor. Fifteen months posttransplantation, the disease relapsed again; however, further salvage therapy successfully induced a third remission. Notably, HLA analysis revealed persistent donor–donor mixed chimerism with one unit maintaining clear dominance. Because no suitable matches existed for the patient’s native HLA type, the dominant donor’s HLA genotype was utilized as the new target for donor selection. This shift facilitated the identification of a matched allogeneic peripheral blood stem cell transplantation (allo‐PBSCT) donor. Conclusion The patient subsequently underwent a second allo‐PBSCT based on the dominant donor’s HLA profile. The procedure resulted in robust engraftment and complete donor chimerism without the occurrence of graft‐versus‐host disease. The patient has remained in relapse‐free survival for over 4 years. This case demonstrates that in the rare event of persistent donor–donor chimerism post‐dCBT, the emergent dominant HLA genotype can serve as a viable and effective target for donor selection, providing a life‐saving alternative for patients who lack native HLA‐matched donors.