Transplantation of highly purified CD34东1 hematopoietic
stem cells in patients with metastatic breast cancer.
Negrin RS, Atkinson K, Leemhuis T, Hanania E, Juttner C,
Tierney K, Hu WW, Johnston LJ, Shizurn JA, Stockerl-Goldstein KE, Blume KG,
Weissman IL, Bower S, Baynes R, Dansey R, Karanes C, Peters W, Klein J
Division of Bone Marrow Transplantation, Department of Medicine,
Stanford University Medical Center, Stanford, California USA.
NegRS@Leland.Stanford.edu
[Medline record in process]
We report
here the transplantation of extensively purified "mobilized" peripheral blood
CD34Thy-1 hematopoietic stem cells from 22 patients with recurrent or metastatic
breast cancer. Patients were mobilized with either high-dose granulocyte
colony-stimulating factor (G-CSF) alone or cyclophosphamide plus G-CSE Median
purity of the stem cell product at cryopreservation was 95.3% (range,
91.1%-98.3%), and viability was 98.6% (range, 96.5%-100%). After high-dose
chemotherapy with carmustine, cisplatin, and cyclophosphamide, CD34东1 cells at a
median dose of 11.3 x 105 per kilogram (range, 4.7-163 x 105 per kilogram) were
infused. No infusion-related toxicity was observed. Neutrophil recovery was
prompt, with median absolute neutrophil count >500/microL by day 10 (range,
8-15 days) and >1000/microL by day 11 (range, 8-17 days). Median platelet
recovery (>20,000/microL) was observed by day 14 (range, 9-42 days) and
>50,000/microL by day 17 (range, 11-49 days). Tumor cell depletion below the
limits of detection of a sensitive immunofluorescence-based assay was
accomplished in all patients who had detectable tumor cells in apheresis
products before processing. Although CD4 T-cell reconstitution was slow, no
unusual infections were observed. Neither early nor late graft failure was
observed, and no patient required infusion of unmanipulated backup cells. At a
median follow-up of approximately 1.4 years and a maximum follow-up of 2.5
years, 16 of the 22 patients remain alive, with 9 free of disease progression,
and have stable blood counts. In summary, highly purified CD34东1 cells used as
the sole source of the hematopoietic graft result in rapid and sustained
hematopoietic engraftment.