Double-Unit Cord Blood Transplantation in Japan.

Cord blood (CB) is being increasingly used as a source of hematopoietic stem cells for patients in need of stem cell transplantation when a HLA matched-related or unrelated donor is not found. However, cord blood transplantation (CBT) in adults is limited by its lower cell dose. We have started investigating whether transplant with two units of CB will make an engraftment faster and improve outcomes in adult patient lacking a suitable single CB unit. Four transplant centers have participated in this clinical study. Eligibility for this study are as follows; 1) high-risk or advanced hematological malignancy without a related donor, 2) no HLA-matched unrelated BM donor in JMDP or requirement for urgent transplantation, and 3) absence of single HLA 0–2 antigen-mismatched cord blood unit with a cell dose of >2.5x10e7/kg. Eleven patients with hematological malignancies (AML 7, MLL 2, ALL 1, LBL 1) were transplanted with two CB units, following myeloablative conditioning with fractionated TBI(12Gy)+ G-CSF (5?g/kg/dx2days) combined ara-C (12g/?) +CY (120mg/kg) or TBI(12Gy) + CY (120mg/kg). GVHD prophylaxis consisted of short term MTX and CSA. The median age was 33 years (range; 19–52) and median weight was 68kg (range 48– 84). CB grafts were HLA 0–2 antigen-mismatched to the patients and each other, with a median total cryopreserved cell dose of 3.88x10e7/kg (range; 2.83–4.79) and median CD34+ cell dose of 1.06x10e5/kg (0.62–2.6). Nine out of 11 patients engrafted successfully, and had 96–100% single donor chimerism at day+28 bone marrow aspirate. The median time to neutrophil engraftment (ANC >500 /?) was 21days (16–26) and median time to platelets >50000 /?was 53 days (32–98). Nine patients who survived more than 28 days had AGVHD (grade I in 2, II in 3, III in 1), and CGVHD (limited type) was developed in 4 of the 6 evaluable patients. Two patients died of sepsis at day 7 and 27 and one had relapse at day 249. Nine patients are now alive 3 to 16 months after CBT. These preliminary results suggest that multiple unit CBT seems to be useful for adult with hematological malignancies lacking an appropriate BM donor or a single CB unit. Further studies with double-unit CBT may be warranted.