1. Unrelated adult cord blood transplants for adults with acute leukemia (2005)

Unrelated cord blood transplant is an option for adults who lack an HLA identical bone marrow donor. Eurocord has analyzed results in 171 patients with malignancies and compared with HLA identical unrelated bone marrow transplant or to haploidentical peripheral blood related transplants. Results in adults: One-hundred and seventy one patients were transplanted after 1997. Median age was 29 years (15-55), and median follow-up time was 18 months (1-71). Most patients had acute or chronic leukemia (n = 142, 83%), 91 (53%) were transplanted in advanced phase and 32 (19%) had failed an autologous transplant. Most patients (87%) received an HLA incompatible CB unit with 1-2 HLA mismatches. At infusion, the median number of nucleated cells (NC) and CD34+ cells was 2.1 × 107/kg and 1 × 105/kg, respectively. The cumulative incidence (CI) of neutrophil recovery at day 60 was 72 ± 3% with a median of 28 days (11-57). A higher NC and use of hematopoietic growth factors were independently associated with faster neutrophil recovery. The CI of grade II-IV acute-GVHD was 32 ± 4% and it was not associated with the number of HLA mismatches. The 2-year CI of chronic-GVHD, transplant-related-mortality and relapse were 36 ± 10%, 51 ± 4% and 22 ± 4%, respectively. At 2-years, disease-free-survival (DFS) for patients transplanted in early, intermediate and advanced phase of disease was 41 ± 9%, 34 ± 10% and 18 ± 4%, respectively. In multivariate analyses, advanced status of the disease was an adverse factor for relapse and DFS. Comparison with HLA identical unrelated bone marrow transplants: Eurocord and EBMT have performed a matched pair analysis to compare the results of UCB and BMT from unrelated donors in adults with acute leukemia. Eighty-one patients receiving unrelated donor UCB (90% HLA-mismatched) were matched for age, diagnosis, status of disease at transplant and use of total body irradiation and compared with 162 recipients of unmanipulated HLA-matched unrelated donor BM. Neutrophil recovery was delayed in recipients of UCB and incidence of acute GVHD ≥ grade II was higher in those receiving BM. The 2-year cumulative incidence of chronic GVHD, TRM, leukemia relapse, 2-year probability of survival and leukemia-free survival were not significantly different. Comparison with haploidentical related peripheral blood transplant: We have compared the outcome in 229 patients receiving a haplo mismatched related transplant to 139 patients who received a mismatched unrelated cord blood transplant. There were 220 AML and 148 ALL which were analyzed separately. In AML, engraftment was faster in patients with haplo transplant. There was more GVH in the UCBT group (23 vs 5%). Transplant related mortality (58 vs 46%) and rate of relapse (24 vs 18%) were not different. Leukemia free survival was identical (30 vs 24%). In ALL engraftment and GVH rates were similar to the AML patients, TRM was identical after haplo or CB. LFS was higher in CB than in haplo (36 vs 13%). The difference was more significant in patients transplanted in CR2 or more advanced disease. Conclusion: UCBT is a clear alternative for adults with hematological malignancies lacking an HLA-matched related or unrelated donor. These data suggest that, despite increased HLA disparity, UCB from unrelated donors offers comparable results to matched unrelated BM in adults with acute leukemia, leading to the conclusion that the donor search process for BM and UCB from unrelated donors should be started simultaneously in adults, especially in patients with acute leukemia where the time factor is very important. The choice of units containing a higher NC and a policy of earlier transplantation are likely to provide better results.