There is evidence that the total cellular content of placental cord blood (PCB) grafts is related to the speed of engraftment, though the total nucleated cell (TNC) dose is not a precise predictor of the time of neutrophil or platelet engraftment. It is important to understand the reasons for the quantitative association and to improve the criteria for selecting PCB grafts by using indices more precisely predictive of engraftment. The posttransplant course of 204 patients who received grafts evaluated for hematopoietic colony-forming cell (CFC) content among 562 patients reported previously were analyzed using univariate and multivariate life-table techniques to determine whether CFC doses predicted hematopoietic engraftment speed and risk for transplant-related events more accurately than the TNC dose. Actuarial times to neutrophil and platelet engraftment were shown to correlate with the cell dose, whether estimated as TNC or CFC per kilogram of recipient's weight. CFC association with the day of recovery of 500 neutrophils/μL, measured as the coefficient of correlation, was stronger than that of the TNC (R = −0.46 and −0.413, respectively). In multivariate tests of speed of platelet and neutrophil engraftment and of probability of posttransplantation events, the inclusion of CFC in the model displaced the significance of the high relative risks associated with TNC. The CFC content of PCB units is associated more rigorously with the major covariates of posttransplantation survival than is the TNC and is, therefore, a better index of the hematopoietic content of PCB grafts.
Cord blood (CB) hematopoietic stem cell transplantation can be successful even if donor and recipient are not fully matched for human leukocyte antigens (HLA). This may result from toleranceinducing events during pregnancy but to date this concept has not been tested in CB transplantation. Hence we analyzed the impact of fetal exposure to noninherited maternal antigens (NIMA) of the HLA-A, -B antigens, or -DRB1 alleles on the outcome of CB transplants. The 1,121 patients studied were transplanted for hematological malignancy with a single CB unit: 1,059 received grafts mismatched for one or two HLA antigens. Of these patients, 79 patients had a mismatched antigen that was identical to a donor NIMA, 25 with one HLA mismatch (MM), and 54 with two. If there was a NIMA match, transplant-related mortality (TRM) was improved, especially in patients >10 years (P ؍ 0.012) as were overall mortality and treatment failure (P ؍ 0.022 and 0.020, respectively, in the older subset), perhaps related to improved neutrophil recovery, especially in patients who received a low total nucleated cell (TNC) dose (P ؍ 0.031). Posttransplant relapse rate also tended to be reduced, especially in patients with myelogenous malignancies given units with a single HLA mismatch (P ؍ 0.074). These findings represent unique evidence that donor exposure to NIMA can improve survival in unrelated CB transplantation and might reduce relapse, indicating that cord blood cells can mount an antileukemic effect. By matching for donor NIMAs in search algorithms of CB inventories, the probability of selecting a graft with an optimal outcome will increase significantly.cord blood transplantation ͉ hematopoietic stem cell transplantation ͉ relapse reducing mechanisms ͉ tolerance
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