Prior chemotherapy and allograft CD34+ dose impact donor engraftment following nonmyeloablative allogeneic stem cell transplantation in patients with solid tumors

Abstract

Abstract Significant engraftment variability occurs among patients following nonmyeloablative hematopoietic cell transplantation. We analyzed the impact of multiple factors on donor myeloid and T-cell engraftment in 36 patients with metastatic tumors undergoing cyclophosphamide/fludarabine-based conditioning. Higher CD34+ doses facilitated donor myeloid engraftment, while prior chemotherapy exposure facilitated both donor myeloid and T-cell engraftment. At day 30, median donor T-cell and myeloid chimerism was 98% and 76%, respectively, in those patients with prior chemotherapy versus 88% (P = .008) and 26% (P < .0001) in chemotherapy-naive patients. Donor myeloid chimerism at day 45 was predicted by prior chemotherapy exposure and the log10 of the CD34+ dose (adjusted coefficient of determination [R2] = .47; P < .0001), while chemotherapy alone impacted donor T-cell engraftment. Patients with prior chemotherapy were more likely to develop acute grades II to IV graft-versus-host disease (GVHD; 8/18) compared with chemotherapy-naive patients (2/18; P = .031). Thus, tailoring the intensity of nonmyeloablative conditioning based on prior chemotherapy exposure is an important consideration in trial design.