Transplantation of enriched CD34-positive autologous marrow into breast cancer patients following high-dose chemotherapy: influence of CD34-positive peripheral-blood progenitors and growth factors on engraftment.
OBJECTIVE
To evaluate the capacity of enriched CD34-positive (CD34+) progenitor cells to reconstitute hematopoiesis in poor-prognosis breast cancer patients following administration of a high-dose alkylating agent chemotherapy regimen.


METHODS
Forty-four breast cancer patients received high-dose chemotherapy followed by autologous bone marrow support (ABMS) with CD34+ hematopoietic progenitor cells in five sequentially treated cohorts. Following infusion of CD34+ marrow, cohort no. 1 received no growth factor, cohort no. 2 received granulocyte colony-stimulating factor (G-CSF), and cohort no. 3 received granulocyte-macrophage colony-stimulating factor (GM-CSF). Cohort no. 4 received the CD34+ fractions of both marrow and peripheral-blood progenitor cells (PBPCs) plus G-CSF. Cohort no. 5 received only the CD34+ PBPCs plus G-CSF. Immunohistochemical staining for breast cancer was performed on all hematopoietic cell products before and after the positive selection procedure, to assess quantitatively the level of tumor-cell contamination.


RESULTS
Cohorts no. 1, 2, 3, 4, and 5 achieved a granulocyte count > or = 500 x 10(9)/L in a median of 23, 10, 16, 11, and 11 days, with a platelet count greater than 20,000 x 10(9)/L documented in a median of 22, 23, 32, 12, and 10 days, respectively. The time to granulocyte reconstitution was significantly shorter for patients who received CD34+ PBPCs alone (cohort no. 5), or in combination with CD34+ marrow (cohort no. 4), when compared with those who received only the CD34+ marrow fraction (P < .01). From 1 to greater than 4 logs of breast cancer cell depletion were documented after CD34-selection, for patients in whom tumor was initially detected.


CONCLUSIONS
CD34+ marrow and/or PBPCs provide reliable and timely hematopoietic reconstitution in breast cancer patients receiving high-dose chemotherapy. Contamination of both marrow and PBPCs with breast cancer cells was reduced using this positive selection technique.
Shpall
E J
EJ
Department of Pathologu, University of Colorado, Denver.
Jones
R B
RB
Bearman
S I
SI
Franklin
W A
WA
Archer
P G
PG
Curiel
T
T
Bitter
M
M
Claman
H N
HN
Stemmer
S M
SM
Purdy
M
M
D000328:Adult; D015703:Antigens, CD; D018952:Antigens, CD34; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D001855:Bone Marrow Diseases / Q000139:chemically induced / Q000517:prevention & control; D016026:Bone Marrow Transplantation; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy*; D003115:Colony-Stimulating Factors / Q000627:therapeutic use*; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged
D015703:Antigens, CD; D018952:Antigens, CD34; D003115:Colony-Stimulating Factors