Placental blood for bone marrow replacement: the New York Blood Center's program and clinical results

Background and objectives: Placental/umbilical cord blood (PCB) has been used for allogeneic bone marrow replacement since 1988. The Placental Blood Program of the New York Blood Center has developed techniques for collecting, testing, freezing and searching units on behalf of unrelated patients in need of hematopoietic stem cell replacement since 1993 and provided analysis of the outcomes of these transplants identified variables associated with clinical outcomes. In this review, after considering practical and conceptual aspects of the technology, we update information on the clinical outcomes of these transplants.

Materials and methods: All 861 patients transplanted through 1999 with PCB from our Program are included in this report. Two thirds were diagnosed with leukaemia or lymphoma, 25% with inherited conditions and 7% with acquired diseases. Outcome data were provided by the respective Transplant Center and analyses included both univariate and multivariate regression tests and actuarial (Kaplan-Meier) techniques.

Results: Engraftment was achieved by over 90% of recipients (Kaplan-Meier estimate). Multivariate analysis confirmed the influence of cell dose, HLA matching, disease diagnosis and transplant center location (US vs. foreign). Patient age and HLA match grade independently affected the frequency and severity of acute graft vs. host disease. Leukaemic relapse was associated with the stage of disease at transplantation and the prior existence of acute graft vs. host disease. The probability of transplant-related events was independently associated with disease diagnosis, cell dose, number of HLA mismatches and transplant center, while the cell dose failed to associate significantly with the relative risk of reaching this endpoint in the subset of patients who achieved engraftment. Overall, event-free survival rates at one year post-transplant were 49 and 30%, respectively for genetic disease and haematologic malignancies and 35% for patients with acquired diseases, respectively.

Conclusions: These results confirm and extend earlier data, particularly establishing the significant association of transplant success with histocompatibility matching grades, and indicatng the urgency of improving the transplant match levels.