Filgrastim mobilization and apheresis of blood stem cells constitute a safe, well-tolerated, and comparable or less expensive alternative to the traditional marrow harvest.
Peripheral blood stem cells (PBSCs) have been used rarely for allogeneic transplantation because of concerns regarding graft failure and graft-versus-host disease (GVHD). We evaluated the results of allogeneic PBSC transplantation (allo-PBSCT) in 9 patients with refractory leukemia or lymphoma receiving myeloablative therapy followed by allo-PBSCT from an HLA-identical sibling donor. Three patients had relapsed 11 to 21 months after allogeneic bone marrow transplantation (allo-BMT) and underwent allo-PBSCT using the same donor. Six patients received PBSCs as their initial allogeneic transplant. Filgrastim-mobilized PBSCs were collected from the donors in 3 to 4 aphereses and cryopreserved. The apheresis collections contained a median nucleated cell count of 16.5 x 10(8)/kg (range, 10.8 to 28.7 x 10(8), 10.7 x 10(6) CD34+ cells/kg (range, 7.5 to 22.5 x 10(6)), and 300.0 x 10(6) CD3+ cells/kg (range, 127.8 to 1,523.2 x 10(6)). The median recovery of CD34+ progenitor cells after freezing, thawing, and washing was 106.4% (range, 36.7% to 132.0%). All patients received filgrastim posttransplant through engraftment, and cyclosporine and methylprednisolone were used for GVHD prophylaxis. Neutrophil recovery to greater than 0.5 x 10(9)/L and greater than 1.0 x 10(9)/L occurred at a median of 9 (range, 8 to 10) and 9 days (range, 8 to 11) posttransplant, respectively, which was similar to historical controls after allo-BMT and granulocyte colony-stimulating factor therapy. Platelets recovered to greater than 20 x 10(9)/L and greater than 50 x 10(9)/L at a median of 12 (range, 8 to 25) and 15 days (range, 11 to 59), respectively, which was significantly more rapid than for the controls (P < .01). Donor cell engraftment was documented by cytogenetics, fluorescence in situ hybridization, and/or restriction fragment length polymorphisms with longest follow-up of 283 + days. Three patients developed grade 2 acute GVHD involving only the skin. Three of five evaluable patients show limited chronic GVHD. Cryopreserved, filgrastim-stimulated allogeneic PBSCs may be a suitable alternative to allogeneic marrow for transplantation with the advantage of more rapid platelet recovery. Acute GVHD was minimal despite the infusion of 1 log more CD3 cells than with marrow allografts. Further studies are required to assess long-term risks of chronic GVHD.
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.
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