Improved mobilization of peripheral blood CD34+ cells and dendritic cells by AMD3100 plus granulocyte-colony-stimulating factor in non-Hodgkin's lymphoma patients

被引:46
作者
Gazitt, Yair
Freytes, Cesar O.
Akay, Cagla
Badel, Karin
Calandra, Gary
机构
[1] Univ Texas, Hlth Sci Ctr, Dept Med Hematol, San Antonio & Audie L Murphy Mem Vet Hosp, San Antonio, TX 78284 USA
[2] AnorMed, Langley, BC, Canada
关键词
D O I
10.1089/scd.2006.0087
中图分类号
Q813 [细胞工程];
学科分类号
摘要
AMD3100 is a drug capable of mobilizing peripheral blood stem cells (PBSCs) in donors and in cancer patients as a single agent or in combination with granulocyte-colony-stimulating factor (G-CSF). We initiated a phase II study of 11 refractory or relapsed non-Hodgkin's lymphoma (NHL) patients, receiving 16 mu g/kg daily of G-CSF for 4 days followed by 240 mu g/kg of AMD3100 given subcutaneously on a new schedule of 9-10 h before apheresis collection on day 5. Our aims were to assess the effect of AMD3100 on the mobilization of CD34(+) cells, dendritic cells (DCs) and lymphoma cells. Administration of G-CSF and AMD3100 were continued daily until >= 2 x 10(6) CD34(+) cells/kg were collected. Adequate collection of the target of CD34(+) cells was achieved in all but 1 patient within 2 days, and 10/11 patients were transplanted within 2 months. All transplanted patients engrafted with a mean of 10 and 12 days for neutrophils and platelets, respectively. Addition of AMD3100 to G-CSF resulted with >2.5-fold increase in CD34(+) cells/mu l (p = 0.0001) and in a >2-fold increase in pDC1 and pDC2 cells/mu l (p = 0.003). Adverse events related to AMD3100 were minimal. AMD3100 was generally safe and improved PBSC and DC cell mobilization with no apparent contamination of lymphoma cells.
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页码:657 / 666
页数:10
相关论文
共 49 条
[1]   Human CD34+ cells express CXCR4 and its ligand stromal cell-derived factor-1.: Implications for infection by T-cell tropic human immunodeficiency virus [J].
Aiuti, A ;
Turchetto, L ;
Cota, M ;
Cipponi, A ;
Brambilla, A ;
Arcelloni, C ;
Paroni, R ;
Vicenzi, E ;
Bordignon, C ;
Poli, G .
BLOOD, 1999, 94 (01) :62-73
[2]   Granulocyte-colony stimulating factor mobilizes T helper 2-inducing dendritic cells [J].
Arpinati, M ;
Green, CL ;
Heimfeld, S ;
Heuser, JE ;
Anasetti, C .
BLOOD, 2000, 95 (08) :2484-2490
[3]  
Avigan D, 1999, CLIN CANCER RES, V5, P2735
[4]  
BERNHARD H, 1995, CANCER RES, V55, P1099
[5]   Rapid mobilization of murine and human hematopoietic stem and progenitor cells with AMD3100, a CXCR4 antagonist [J].
Broxmeyer, HE ;
Orschell, CM ;
Clapp, DW ;
Hangoc, G ;
Cooper, S ;
Plett, PA ;
Liles, WC ;
Li, XX ;
Graham-Evans, B ;
Campbell, TB ;
Calandra, G ;
Bridger, G ;
Dale, DC ;
Srour, EF .
JOURNAL OF EXPERIMENTAL MEDICINE, 2005, 201 (08) :1307-1318
[6]   Stromal-derived factor 1 and matrix metalloproteinase 9 levels in bone marrow and peripheral blood of patients mobilized by granulocyte colony-stimulating factor and chemotherapy.: Relationship with mobilizing capacity of haematopoietic progenitor cells [J].
Carion, A ;
Benboubker, L ;
Hérault, O ;
Roingeard, F ;
Degenne, M ;
Senecal, D ;
Desbois, I ;
Colombat, P ;
Charbord, P ;
Binet, C ;
Domenech, J .
BRITISH JOURNAL OF HAEMATOLOGY, 2003, 122 (06) :918-926
[8]  
DOLKEN L, 1998, BIOTECHNICS, V6, P105
[9]   AMD310, a small molecule inhibitor of HIV-1 entry via the CXCR4 co-receptor [J].
Donzella, GA ;
Schols, D ;
Lin, SW ;
Esté, JA ;
Nagashima, KA ;
Maddon, PJ ;
Allaway, GP ;
Sakmar, TP ;
Henson, G ;
De Clercq, E ;
Moore, JP .
NATURE MEDICINE, 1998, 4 (01) :72-77
[10]  
DUGAN MJ, 2004, AM SOC HEM M