Unrelated Cord Blood Transplantation after Nonmyeloablative Conditioning: Single Institutional Retrospective Comparison with Bone Marrow or Peripheral Blood Stem-Cell Transplants.

Background: Unrelated cord blood transplantation (CBT) has emerged as an effective therapy for treating patients with advanced or high-risk hematologic diseases who have no suitable related or unrelated donor. In older patients or those with extensive prior therapy or other clinical features, nonmyeloablative regimens have been used to reduce the risk of regimen-related toxicity and transplantation-related mortality (TRM). Several studies have been reported on the use of unrelated CBT using various reduced-intensity conditioning regimens.

Objectives: This study aimed to evaluate the safety and efficacy of unrelated CBT after nonmyeloablative conditioning using fludarabine, cyclophosphamide and single fraction of total body irradiation of 200 cGy, compared with bone marrow transplantation (BMT) or peripheral blood stem-cell transplantation (PBSCT) for adult Japanese patients with hematologic diseases and relate those to biological and procedural factors.

Patients and Methods: Clinical data were collected retrospectively on 70 adults with hematologic disease who received unrelated CBT (n=19) or BMT from unrelated donors (n=27), or PBSCT from related donors (n=24) between August 2000 and June 2008 in our institution. All patients received nonmyeloablative conditioning regimens including fludarabine. The median period of follow-up for survivors was 253 days after CBT, 364 days after BMT and 692 days after PBSCT, respectively. We analyzed the hematopoietic recovery, incidence of graft-versus-host disease (GVHD), risks of TRM and relapse, and disease-free survival (DFS) using Cox proportional hazards models.

Results: Comparisons of characteristics in 3 groups showed similar distributions for age, gender ratio, diagnosis, risk of disease at the transplant. Compared with BMT and PBSCT (BMT/PBSCT) recipients, CBT recipients had more previous history of hematopoietic stem cell transplantation (HSCT), less human leukocyte antigen-matched donor and less methotrexate (MTX)-containing GVHD prophylaxis. Multivariate analysis demonstrated slow neutrophil (P<0.01) and platelet (P<0.01) recoveries in CBT compared with BMT/PBSCT. The cumulative incidence of grade II to IV acute GVHD in CBT recipients were significantly higher than those in PBSCT recipients (60% versus 23%, P=0.02), but not significantly different from BMT recipients. The cumulative incidence of extensive-type of chronic GVHD at 1 year in CBT recipients was not significantly different from BMT/PBSCT recipients. No statistically differences were seen in TRM (22% in CBT, 24% in BMT and 9% in PBSCT recipients at 1 years), relapse (38% in CBT, 32% in BMT and 40% in PBSCT recipients at 1 years) and DFS (46% in CBT, 50% in BMT and 46% in PBSCT recipients at 1 years) among 3 groups. Risk of disease at the transplant was the only factor for DFS result (standard versus high, P<0.01).

Conclusion: These data suggest that unrelated cord blood (UCB) after this nonmyeloablative conditioning could be a safe and effective stem cell source similar to bone marrow or mobilized peripheral blood for adult Japanese patients, and also support the use of UCB as a strategy for extending the availability of transplantation therapy, particularly for older patients without suitable related or unrelated blood or bone marrow donor.