Long-lasting decrease of marrow and circulating long-term culture initiating cells after allogeneic bone marrow transplant.
We investigated bone marrow (BM) and circulating (PB) hematopoietic progenitor cells in 37 normal donors and in 25 patients 1 to 8 years after successful allogeneic bone marrow transplant. At the time of testing, transplanted patients had normal blood counts and bone marrow cellularity. By flow cytometry, BM CD34+ cells were found to be three- to four-fold decreased in transplanted patients compared to normal donors, while the number of PB CD34+ cells was the same as in normal donors. Using a methylcellulose colony assay, primary BM colony-forming cells (CFU-GM) were decreased 2.1-fold, whereas PB CFU-GM were only marginally decreased. In a long-term culture initiating cell (LTC-IC) assay, an eight-fold decrease of early progenitor cells was observed in the marrow of transplanted patients compared to normal donors, and a five-fold decrease was documented in peripheral blood. We found that the BM LTC-IC cell number correlated with concurrently determined BM CD34+ cells and committed progenitor cell number (measured as CFU-GM) and with PB LTC-IC number, but not with PB CFU-GM and CD34+ cells. We conclude that marrow and circulating early stem cell compartments, as measured by the LTC-IC assay, are greatly and permanently depressed following bone marrow transplant. The correlation between BM and PB LTC-IC indicates that the enumeration of circulating LTC-IC can be used as a measure of the stem cell compartment in the bone marrow after transplant. It seems that the deficiency of the most immature progenitor cells persists forever after successful bone marrow transplant; this means that a complete hematopoietic reconstitution can be sustained by a reduced stem cell pool.
Selleri
C
C
Division of Hematology, Federico II University School of Medicine, Naples, Italy.
Maciejewski
J P
JP
De Rosa
G
G
Raiola
A
A
Risitano
A M
AM
Picardi
M
M
Pezzullo
L
L
Luciano
L
L
Ricci
P
P
Varriale
G
G
Della Cioppa
P
P
Del Vecchio
L
L
Rotoli
B
B
D000293:Adolescent; D000328:Adult; D018952:Antigens, CD34 / Q000378:metabolism; D001772:Blood Cell Count; D001773:Blood Cells / Q000276:immunology / Q000473:pathology; D016026:Bone Marrow Transplantation / Q000276:immunology / Q000473:pathology*; D002454:Cell Differentiation; D003114:Colony-Forming Units Assay; D005260:Female; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000473:pathology*; D006801:Humans; D007938:Leukemia / Q000097:blood / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D014184:Transplantation, Homologous
D018952:Antigens, CD34