Innovations in allogeneic stem-cell transplantation.
Allogeneic bone marrow transplantation (BMT) is associated with prolonged periods of neutropenia and thrombocytopenia, which can lead to severe infections and bleeding complications. Transplantation-related side effects might be ameliorated by use of cytokine-mobilized peripheral blood progenitor cells (PBPC) Instead of bone marrow. We have studied PBPC mobilization and transplantation in more than 150 patients with high-risk hematologic malignancies. Normal donors can be sufficiently mobilized with granulocyte colony-stimulating factor (G-CSF), with 91% of G-CSF-stimulated normal donors producing more than 2 x 10(6) CD34+ cells/kg by a single apheresis. The combination of G-CSF plus granulocyte-macrophage colony-stimulating factor (GM-CSF) was more effective than mobilization with G-CSF alone. A clear relationship was seen between numbers of resting CD34+ cells premobilization and numbers of PBPC collected by apheresis, indicating that resting CD34+ cells might be used to predict mobilization results and identify donors who could benefit from more effective mobilization regimens. Transplantation of G-CSF-mobilized PBPC was associated with a more rapid engraftment than that observed for BMT. While engraftment was safe and acute graft-versus-host disease (aGvHD) rates were not increased over BMT, chronic GvHD rates were higher after PBPC transplantation. An additional PBPC infusion on day +3 resulted in a further shortening of neutropenia and thrombocytopenia. Incorporation of these innovative approaches with "minimal" conditioning regimens has resulted in near-complete elimination of fever, neutropenia, thrombocytopenia, and the need for antibiotics and RBC and platelet transfusions after allogeneic transplantation.
DiPersio
J F
JF
Division of Bone Marrow Transplantation and Stem Cell Biology, Washington University School of Medicine, St Louis, MO 63110, USA.
Khoury
H
H
Haug
J
J
Vij
R
R
Adkins
D R
DR
Goodnough
L T
LT
Brown
R A
RA
D000818:Animals; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology / Q000627:therapeutic use; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology / Q000627:therapeutic use; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D014184:Transplantation, Homologous / Q000009:adverse effects
D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor