title: Prior chemotherapy and allograft CD34+ dose impact donor engraftment following nonmyeloablative allogeneic stem cell transplantation in patients with solid tumors.
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 log(10) of the CD34(+) dose (adjusted coefficient of determination [R(2)] =.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.
authors.affiliation: Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1652, USA.
authors.forename: Cristian
authors.initials: C
authors.lastname: Carvallo
authors.forename: Nancy
authors.initials: N
authors.lastname: Geller
authors.forename: Roger
authors.initials: R
authors.lastname: Kurlander
authors.forename: Ramaprasad
authors.initials: R
authors.lastname: Srinivasan
authors.forename: Othon
authors.initials: O
authors.lastname: Mena
authors.forename: Takehito
authors.initials: T
authors.lastname: Igarashi
authors.forename: Linda M
authors.initials: LM
authors.lastname: Griffith
authors.forename: W Marston
authors.initials: WM
authors.lastname: Linehan
authors.forename: Richard W
authors.initials: RW
authors.lastname: Childs
mesh_terms: D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000032:analysis; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001792:Blood Platelets; D003131:Combined Modality Therapy; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000737:chemistry; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D012044:Regression Analysis; D013601:T-Lymphocytes / Q000276:immunology; D018183:Transplantation Chimera; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous
chemical_list: D018952:Antigens, CD34; D000970:Antineoplastic Agents