Clonal expansion and evolution after graft failure and autologous gene therapy. HSCs can acquire deleterious mutations during the normal course of life of an individual or as a result of exposure to chemotherapy and radiation during conditioning for an allogeneic HCT. HSCs that have acquired deleterious mutations may preferentially expand during the phase of regenerative hematopoiesis after graft failure with an allogeneic HCT. These clonally expanded HSCs, along with normal stem cells, may be collected during apheresis, be genetically modified, and then be reinfused into the patient to reconstitute the entire hematopoietic system after gene therapy. During this second cycle of regenerative hematopoiesis, HSCs with a mutation that confers a relative growth advantage may continue to expand clonally and predispose the individual to developing a hematologic malignancy.