title: Results of MDR-1 vector modification trial indicate that granulocyte/macrophage colony-forming unit cells do not contribute to posttransplant hematopoietic recovery following intensive systemic therapy.
abstract: To formally test the hypothesis that the granulocyte/macrophage colony-forming unit (GM-CFU) cells can contribute to early hematopoietic reconstitution immediately after transplant, the frequency of genetically modified GM-CFU after retroviral vector transduction was measured by a quantitative in situ polymerase chain reaction (PCR), which is specific for the multidrug resistance-1 (MDR-1) vector, and by a quantitative GM-CFU methylcellulose plating assay. The results of this analysis showed no difference between the transduction frequency in the products of two different transduction protocols: "suspension transduction" and "stromal growth factor transduction." However, when an analysis of the frequency of cells positive for the retroviral MDR-1 vector posttransplantation was carried out, 0 of 10 patients transplanted with cells transduced by the suspension method were positive for the vector MDR-1 posttransplant, whereas 5 of 8 patients transplanted with the cells transduced by the stromal growth factor method were positive for the MDR-1 vector transcription unit by in situ or in solution PCR assay (a difference that is significant at the P = 0.0065 level by the Fisher exact test). These data suggest that only very small subsets of the GM-CFU fraction of myeloid cells, if any, contribute to the repopulation of the hematopoietic tissues that occurs following intensive systemic therapy and transplantation of autologous hematopoietic cells.
authors.affiliation: University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
authors.forename: E G
authors.initials: EG
authors.lastname: Hanania
authors.forename: R E
authors.initials: RE
authors.lastname: Giles
authors.forename: J
authors.initials: J
authors.lastname: Kavanagh
authors.forename: S Q
authors.initials: SQ
authors.lastname: Fu
authors.forename: D
authors.initials: D
authors.lastname: Ellerson
authors.forename: Z
authors.initials: Z
authors.lastname: Zu
authors.forename: T
authors.initials: T
authors.lastname: Wang
authors.forename: Y
authors.initials: Y
authors.lastname: Su
authors.forename: A
authors.initials: A
authors.lastname: Kudelka
authors.forename: Z
authors.initials: Z
authors.lastname: Rahman
authors.forename: F
authors.initials: F
authors.lastname: Holmes
authors.forename: G
authors.initials: G
authors.lastname: Hortobagyi
authors.forename: D
authors.initials: D
authors.lastname: Claxton
authors.forename: C
authors.initials: C
authors.lastname: Bachier
authors.forename: P
authors.initials: P
authors.lastname: Thall
authors.forename: S
authors.initials: S
authors.lastname: Cheng
authors.forename: J
authors.initials: J
authors.lastname: Hester
authors.forename: J M
authors.initials: JM
authors.lastname: Ostrove
authors.forename: R E
authors.initials: RE
authors.lastname: Bird
authors.forename: A
authors.initials: A
authors.lastname: Chang
authors.forename: M
authors.initials: M
authors.lastname: Korbling
authors.forename: D
authors.initials: D
authors.lastname: Seong
authors.forename: R
authors.initials: R
authors.lastname: Cote
authors.forename: T
authors.initials: T
authors.lastname: Holzmayer
authors.forename: A B
authors.initials: AB
authors.lastname: Deisseroth
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis* / Q000235:genetics; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001483:Base Sequence; D001853:Bone Marrow / Q000473:pathology*; D016026:Bone Marrow Transplantation / Q000502:physiology; D001943:Breast Neoplasms / Q000188:drug therapy / Q000628:therapy*; D003114:Colony-Forming Units Assay; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000627:therapeutic use; D017931:DNA Primers; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D015316:Genetic Therapy; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000628:therapy*; D016133:Polymerase Chain Reaction
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D017931:DNA Primers; D005047:Etoposide; D003520:Cyclophosphamide