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 progeni tor cells in 37 normal donors and in 25 patients 1 to 8 years after success ful allogeneic bone marrow transplant, At the time of testing, transplanted patients had normal blood counts and bone marrow cellularity. By flow cyto metry, BM CD34(+) cells were found to be three- to four-fold decreased in t ransplanted 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, wh ereas PB CFU-GM were only marginally decreased, In a long-term culture init iating cell (LTC-IC) assay, an eight-fold decrease of early progenitor cell s was observed in the marrow of transplanted patients compared to normal do nors, 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 conclu de that marrow and circulating early stem cell compartments, as measured by the LTC-IC assay, are greatly and permanently depressed following bone mar row 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 cel l compartment in the bone marrow after transplant. It seems that the defici ency of the most immature progenitor cells persists forever after successfu l bone marrow transplant; this means that a complete hematopoietic reconsti tution can be sustained by a reduced stem cell pool.