The Comparative Analysis of Bone Marrow Transplantation and Cord Blood Transplantation from Unrelated Donors in Patients with Myelodysplastic Syndrome in Japan.

Background: Allogeneic stem cell transplantation currently is the only potentially curative therapy for myelodysplastic syndrome (MDS). Cord blood and bone marrow from unrelated donors are considered as an acceptable alternative to hematopoietic stem cells. The result of single institutional analysis in Japan has shown cord blood transplantation (CBT) is promising in adults with hematologic malignancies including MDS and is comparable with bone marrow transplantation (BMT) from unrelated or related donors (

Objectives: This study aimed to use the data of MDS patients within JMDP and JCBBN registry database to evaluate safety and efficacy of both BMT and CBT from unrelated donors and relate those to biological and procedural factors.

Methods: Clinical data of 965 patients with MDS including transformed acute myelogenous leukemia (AML/MDS) who received unrelated BMT (n=532) or unrelated CBT (n=433) between 1993 and 2006 were collected. The median period of follow-up for survivors after BMT was 21 months for BMT and 12 month for CBT, respectively. We analyzed the hematopoietic recovery, incidences of graft-versus-host disease (GVHD), risks of transplant-related mortality (TRM) and relapse, and disease-free survival (DFS) using Cox proportional hazards models.

Results: Compared with BMT recipients, CBT recipients were older (52 years old versus 39 years old), included many patients with AML/MDS (58% versus 38%), used many non-myeloablative regimen (55% versus 18%), less human leukocyte antigen-matched donor (3% versus 67%) and less methotrexate (MTX)-containing GVHD prophylaxis (43% versus 91%). Multivariate analysis demonstrated slow neutrophil (P<0.01) and platelet (P<0.01) recoveries in CBT compared with BMT. The incidences of acute and chronic GVHD were not significantly different. Unrelated BMT showed better TRM (25% versus 38% at 1 year, P<0.01), relapse (15% versus 26% at 3 years, P<0.01) and DFS (57% versus 29% at 3 years, P<0.01) results compared with CBT. Next, we analyzed 397 BMT (n=277) and CBT (n=116) recipients who have taken total body irradiation (>8Gy) containing myeloablative regimen and calcineurin inhibitors (cyclosporine or tacrolimus) plus MTX for GVHD prophylaxis without history of prior transplants. In this subpopulation, multivariate analysis revealed no significant difference between BMT and CBT in DFS (59% and 52% at 3 years, respectively). History of chemotherapy before transplant and risk of disease at the transplant were factors affected for DFS results. No statistically difference was also seen in TRM (25% at 1 year after BMT and 24% at 1 year after CBT, respectively). However, the cumulative incidence of relapse was lower in BMT than in CBT (15% and 21% at 3 years, respectively) and this was significantly different by multivariate analysis.

Conclusion: The current Japanese registration data showed overall results of unrelated BMT were better than those of unrelated CBT in MDS. These data also suggest that unrelated CBT could be safely and effectively used for patients with MDS as unrelated BMT when adequate transplant procedures are selected. Myeloablative conditioning regimen including TBI and calcineurin inhibitors plus MTX for GVHD prophylaxis might be promising and the results of prospective clinical studies are warranted.