Early Secondary Graft Failure After Complete Donor Chimerism with Autologous Recovery Following Haploidentical HSCT for Relapsed B-ALL

Abstract

Secondary graft failure after initial donor engraftment is a rare complication of allogeneic hematopoietic stem cell transplantation (HSCT). We report a 47-year-old man with Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia (B-ALL) who underwent haploidentical sibling peripheral blood HSCT after second complete remission. Neutrophil engraftment occurred by Day +14 with platelet engraftment by Day +18. Beginning Day +22, recurrent fever with progressive cytopenias developed. Day +30 peripheral blood short tandem repeat (STR) analysis showed complete donor chimerism; however, cytomegalovirus (CMV) DNAemia increased to 3,736 IU/mL, prompting therapeutic valganciclovir. Bone marrow biopsy on Day +37 showed hypocellular marrow without residual disease, although bone marrow X/Y fluorescence in situ hybridization (FISH) demonstrated 100% XY signals despite a female donor, indicating graft loss. Septic shock developed on Day +48. Management included growth factors, temporary tacrolimus withdrawal, antibiotics, granulocyte infusions, and a stem cell boost on Day +62. Repeat peripheral blood chimerism by Day +95 showed complete recipient genotype, confirming secondary graft failure with autologous reconstitution. Follow-up through Day +183 confirmed sustained autologous hematopoiesis with no relapse or graft-versus-host disease (GVHD). This case highlights an uncommon transition from donor-type marrow failure to autologous recovery and underscores the importance of bone marrow-based chimerism monitoring in cytopenic post-transplant patients.