title: Transplantation of highly purified CD34+Thy-1+ hematopoietic stem cells in patients with metastatic breast cancer.
abstract: We report here the transplantation of extensively purified "mobilized" peripheral blood CD34Thy-1 hematopoietic stem cells from 22 patients with recurrent or metastatic breast cancer. Patients were mobilized with either high-dose granulocyte colony-stimulating factor (G-CSF) alone or cyclophosphamide plus G-CSE Median purity of the stem cell product at cryopreservation was 95.3% (range, 91.1%-98.3%), and viability was 98.6% (range, 96.5%-100%). After high-dose chemotherapy with carmustine, cisplatin, and cyclophosphamide, CD34+Thy-1 cells at a median dose of 11.3 x 10(5) per kilogram (range, 4.7-163 x 10(5) per kilogram) were infused. No infusion-related toxicity was observed. Neutrophil recovery was prompt, with median absolute neutrophil count >500/microL by day 10 (range, 8-15 days) and >1000/microL by day 11 (range, 8-17 days). Median platelet recovery (>20,000/microL) was observed by day 14 (range, 9-42 days) and >50,000/microL by day 17 (range, 11-49 days). Tumor cell depletion below the limits of detection of a sensitive immunofluorescence-based assay was accomplished in all patients who had detectable tumor cells in apheresis products before processing. Although CD4+ T-cell reconstitution was slow, no unusual infections were observed. Neither early nor late graft failure was observed, and no patient required infusion of unmanipulated backup cells. At a median follow-up of approximately 1.4 years and a maximum follow-up of 2.5 years, 16 of the 22 patients remain alive, with 9 free of disease progression, and have stable blood counts. In summary, highly purified CD34+Thy-1+ cells used as the sole source of the hematopoietic graft result in rapid and sustained hematopoietic engraftment.
authors.affiliation: Division of Bone Marrow Transplantation, Department of Medicine, Stanford University Medical Center, Stanford, California USA. NegRS@Leland.Stanford.edu
authors.forename: R S
authors.initials: RS
authors.lastname: Negrin
authors.forename: K
authors.initials: K
authors.lastname: Atkinson
authors.forename: T
authors.initials: T
authors.lastname: Leemhuis
authors.forename: E
authors.initials: E
authors.lastname: Hanania
authors.forename: C
authors.initials: C
authors.lastname: Juttner
authors.forename: K
authors.initials: K
authors.lastname: Tierney
authors.forename: W W
authors.initials: WW
authors.lastname: Hu
authors.forename: L J
authors.initials: LJ
authors.lastname: Johnston
authors.forename: J A
authors.initials: JA
authors.lastname: Shizurn
authors.forename: K E
authors.initials: KE
authors.lastname: Stockerl-Goldstein
authors.forename: K G
authors.initials: KG
authors.lastname: Blume
authors.forename: I L
authors.initials: IL
authors.lastname: Weissman
authors.forename: S
authors.initials: S
authors.lastname: Bower
authors.forename: R
authors.initials: R
authors.lastname: Baynes
authors.forename: R
authors.initials: R
authors.lastname: Dansey
authors.forename: C
authors.initials: C
authors.lastname: Karanes
authors.forename: W
authors.initials: W
authors.lastname: Peters
authors.forename: J
authors.initials: J
authors.lastname: Klein
mesh_terms: D000328:Adult; D000368:Aged; D018952:Antigens, CD34; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000473:pathology / Q000628:therapy*; D002330:Carmustine / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D014182:Transplantation, Autologous
chemical_list: D018952:Antigens, CD34; D003520:Cyclophosphamide; D002945:Cisplatin; D002330:Carmustine