Correlations between progenitor cell dose, likelihood to engraft and time to myeloid engraftment in 79 unrelated placental/cord blood transplants

The placental/cord blood stem cell program of The New York Blood Center has now supported over 300 unrelated transplants. Up to November, 1996, units collected were routinely characterized for their volume and white blood cell (WBC) content and only selected units (all the units of 40-60 ml and random units > 60 ml) were also assayed for their colony forming cell (CFC) content in standardized semisolid cultures. Of the 281 patients transplanted as of 10/31/96, for example, CFC counts are available on 79 units. Most of these units (67%) had a volume < 60 ml. The analysis of (he transplant outcome in this patient population is very interesting because of the generally small volume of cord blood grafted. Of these 79 transplants, 17 (21.5%) are either not informative for engraftment because the patients died before 30 days, or did not engraft. Sixty two patients (78.5%) did engraft. There was no correlation between WBC dose per Kg of body weight and likelihood to engraft in this patient population. In contrast, ihere was a strong and direct correlation between the CFC dose of the unit and the likelihood of engraftment (p=0.002); only 52i of the patients who received < 4x10 CFC/Kg engrafted while more than 80% of the patients receiving more than this dose engrafted. One unit, whose CFC count was below the level of detection (< 2.5 CFC/ul) did engraft, although an absolute neutrophil count (ANC) of > 500/u,l was observed very late (at 41 days). This prompted us to analyze the correlation between the cell content of the graft and the time to ANC >500. The time to ANC >500 for 58 patients averaged 25.8±9.9 days (range 12 to 59) and it was correlated inversely with the nucleated cell dose per Kg (p = 0.01) and with the CFC dose per Kg (p 0.001 ) but not with the graft volume {p = 0.8). The lack of correlation with the graft volume is probably due to the fact that most of the volumes were between 40 and 60 ml. Since the WBC and CFC doses per Kg used in this study are strongly associated with the patients' weight, we also examined the association between the concentration of cells and speed of myeloid engraftment. There was a significant inverse correlation with CFC/ml (p = 0.004) but a statistically insignificant relationship with WBC/ml (p = 0.66). Thus, in cord blood transplantation, the dose of progenitor cells, as measured in colony assays, is directly associated with the likelihood to engraft and inversely correlated with the speed of myeloid engraftment. This association, based on the largest sample population analyzed so far, suggests that ex-vivo expansion of at least some cord blood samples before transplantation could contribute to decrease the time of myeloid engraftment.