Target Dose for PBSC Infusion

When bone marrow is collected, most operators target a final volume, or more commonly, a volume and a nucleated cell dose. Because of the high variability in stem and progenitor cell content in PBSC, a more direct assay is needed to assure that adequate numbers for reliable engraftment have been collected. There is no well-established assay for human stem cells, although stem cell activity is likely to be found in a portion of cells that are detected by the long-term culture initiating cell assay or the SCID mouse repopulating cell assay. Progenitor cell content can be assessed by the colony-forming unit granulo-cyte/monocyte (CFU-GM) assay. The presence of 2-10X104 CFU-GM/kg of recipient weight is predictive of engraftment, but the assay is laborious,expen-sive, and difficult to standardize. It also takes 14 days to complete, making it useless to assess PBSC collections in real time. For all these reasons, most centers have moved away from CFU-GM assays.

A major advance in the use of PBSC was the recognition that most (although not all) (Goodell et al. 1997) of the cells in the hematopoietic stem- and progenitor cell compartment bear the antigen CD34, regardless of lineage. Enumeration of CD34+ cells allows for more accurate assessment of engraftment potential provided by a given number of mononu-clear cells. There is a threshold for reliable engraft-ment and a rough correlation between number of CD34+ cells above this threshold and engraftment (Table 11.6.4). The threshold for reliable engraftment is generally thought to be 1x106 CD34+ cells/kg (Shpall et al. 1998). Below this threshold, the likelihood of delayed engraftment of neutrophils and especially platelets increases (Weaver et al. 1997). Increasing the minimum acceptable number to 2-2.5X106 CD34+ cells/kg decreases this likelihood somewhat further, and this is the threshold that most transplant centers attempt to achieve. Some authors

Cyclophosphamide 2000 mg/m2 day-1 over 2 days, followed by G-CSF 5 mg/kg day-1 SQ from day 3 to the end of pheresis

G-CSF 5 mg/kg day-1 SQ for 3-4 days,followed by pheresis on days 4-5 and subsequently

GM-CSF 250 mg/m2 day-1 SQ for 3-4 days, followed by pheresis on days 4-5 and subsequently

Combination of G-CSF 5-10 mg/kg day-1 (SQ in AM) and GM-CSF 250 mg/m2 day-1 (SQ in PM) for 4 days, pheresis starting on day 5

Other chemotherapy/HGF combinations

Table 11.6.4 Choosing doses of PBSC for stem-cell transplantation

Dose level

CD34+ cells/kg of recipient weight

Notes

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