title: Leukemia cell mobilization with G-CSF plus plerixafor during busulfan-fludarabine conditioning for allogeneic stem cell transplantation.
abstract: We hypothesized that during conditioning chemotherapy for allogeneic stem cell transplant (allo-SCT), the disruption of stromal-leukemia interactions using G-CSF in combination with the CXCR4-specific inhibitor, plerixafor, may promote the release of leukemic cells from the niche and increase tumor elimination. In a phase 1/2 investigation, we treated 45 AML/myelodysplastic syndrome (MDS)/CML patients (34 AML, 7 MDS and 4 CML) with G-CSF (10 μg/kg daily for 6 days starting on day -9) plus plerixafor (doses of 0, 80, 160 or 240 μg/kg daily for 4 days starting on day -7) along with the busulfan-fludarabine (Bu-Flu) conditioning regimen. In the phase 1 part, we determined that G-CSF plus plerixafor is safe in this setting. We compared the clinical effects and outcomes of AML/MDS study patients (n=40) with 164 patients from a historical data set who received Bu-Flu alone before allo-SCT by stratifying on cytogenetics and disease status to correct for bias. Study patients had increased myeloid chimerism and lower rates of GvHD. There was no significant difference in relapse-free survival or overall survival. The G-CSF plus plerixafor combination increased circulating WBCs, CD34+ cells and CXCR4+ cells, and preferentially mobilized FISH+ leukemic cells.
authors: Department of Stem Cell Transplantation, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.|Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
authors: Marina
authors: M
authors: Konopleva
authors: Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
authors: Christopher B
authors: CB
authors: Benton
authors: Department of Biostatistics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
authors: Peter F
authors: PF
authors: Thall
authors: Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
authors: Zhihong
authors: Z
authors: Zeng
authors: Department of Stem Cell Transplantation, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
authors: Elizabeth
authors: E
authors: Shpall
authors: Department of Stem Cell Transplantation, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
authors: Stefan
authors: S
authors: Ciurea
authors: Department of Stem Cell Transplantation, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
authors: Partow
authors: P
authors: Kebriaei
authors: Department of Stem Cell Transplantation, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
authors: Amin
authors: A
authors: Alousi
authors: Department of Stem Cell Transplantation, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
authors: Uday
authors: U
authors: Popat
authors: Department of Stem Cell Transplantation, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
authors: Paolo
authors: P
authors: Anderlini
authors: Department of Stem Cell Transplantation, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
authors: Yago
authors: Y
authors: Nieto
authors: Department of Stem Cell Transplantation, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
authors: Simrit
authors: S
authors: Parmar
authors: Department of Biostatistics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
authors: Wei
authors: W
authors: Qiao
authors: Department of Stem Cell Transplantation, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
authors: Julianne
authors: J
authors: Chen
authors: Department of Stem Cell Transplantation, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
authors: Gabriela
authors: G
authors: Rondon
authors: Department of Stem Cell Transplantation, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
authors: Becky
authors: B
authors: McMullin
authors: Department of Stem Cell Transplantation, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
authors: Rui-Yu
authors: RY
authors: Wang
authors: Department of Stem Cell Transplantation, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
authors: Hongbo
authors: H
authors: Lu
authors: Department of Stem Cell Transplantation, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
authors: Wendy
authors: W
authors: Schober
authors: Department of Stem Cell Transplantation, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
authors: Glenda
authors: G
authors: Woodworth
authors: Division of Pharmacy, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
authors: Alison
authors: A
authors: Gulbis
authors: Division of Pharmacy, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
authors: Rita
authors: R
authors: Cool
authors: Department of Stem Cell Transplantation, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.|Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
authors: Michael
authors: M
authors: Andreeff
authors: Department of Stem Cell Transplantation, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
authors: Richard
authors: R
authors: Champlin
mesh_terms: D000328:Adult; D000368:Aged; D001596:Benzylamines; D002066:Busulfan / Q000008:administration & dosage / Q000627:therapeutic use*; D002465:Cell Movement; D000080027:Cyclams; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000627:therapeutic use*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006571:Heterocyclic Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000628:therapy; D008297:Male; D008875:Middle Aged; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous / Q000379:methods*; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D001596:Benzylamines; D000080027:Cyclams; D006571:Heterocyclic Compounds; D016179:Granulocyte Colony-Stimulating Factor; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine; C088327:plerixafor