Large-scale expansion and transplantation of CD34(+) hematopoietic cells: in vitro and in vivo confirmation of neutropenia abrogation related to the expansion process without impairment of the long-term engraftment capacity.
BACKGROUND
Herein are reported the results obtained in all multiple myeloma patients transplanted with peripheral blood hematopoietic progenitor cells submitted to ex vivo expansion.


METHODS
Patients had blood progenitor cell mobilization with cyclophosphamide and filgrastim. CD34+ cells were expanded for 10 days in a medium containing granulocyte-colony-stimulating factor (G-CSF), stem cell factor, and megakaryocyte growth and development factor (MGDF). Twenty-seven patients underwent transplantation with expanded and nonexpanded cells and 7 patients underwent transplantation with expanded cells only.


RESULTS
The median fold cell expansion was 29.1. The number of colony-forming unit-granulocyte-macrophage (CFU-GM) and CD34+ cells, and the long-term culture-initiating cell (LTC-IC) activity increased with median fold values of 14.7, 2.75, and 2.25, respectively. Postmyeloablative neutropenia was abrogated in 24 of 27 patients transplanted with expanded cells plus nonexpanded cells. The median duration of severe neutropenia was 0 days and correlated with the number of cells and CFU-GM infused. Survival was similar to that of a historical control group. Our LTC-IC and NOD-SCID mice studies showed that the expanded cells are able of sustaining long-term hematopoiesis. Seven other patients received transplantation with expanded cells alone. Absolute neutropenia was abrogated in 6 patients. The median duration of neutropenia was 0 days. Two patients who received the lower number of total cells or CFU-GM had brief secondary neutropenia, which resolved after G-CSF injections.


CONCLUSIONS
CD34+ cells expanded ex vivo can abrogate absolute and severe neutropenia after high-dose therapy. The results of the amplification process are strongly related to the delay of hematopoietic recovery.
Boiron
Jean-Michel
JM
CHU Bordeaux, Pessac, France. jean-michel.bciron@efs.sante.fr
Dazey
Bernard
B
Cailliot
Christian
C
Launay
Béatrice
B
Attal
Michel
M
Mazurier
Frédéric
F
McNiece
Ian K
IK
Ivanovic
Zoran
Z
Caraux
Jean
J
Marit
Gérald
G
Reiffers
Josy
J
D000328:Adult; D018952:Antigens, CD34; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D000069585:Filgrastim; D006085:Graft Survival / Q000187:drug effects; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D042381:Granulocyte Precursor Cells / Q000637:transplantation; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000150:complications / Q000628:therapy*; D009503:Neutropenia / Q000209:etiology / Q000628:therapy*; D036102:Peripheral Blood Stem Cell Transplantation; D011994:Recombinant Proteins; D014182:Transplantation, Autologous
D018952:Antigens, CD34; D018906:Antineoplastic Agents, Alkylating; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D003520:Cyclophosphamide; D000069585:Filgrastim