Unrelated cord blood transplantation after myeloablative conditioning in adult patients with acute leukemia

Abstract

Although allogeneic stem cell transplantation from a human leukocyte antigen (HLA)-identical related donor offers a potential cure for patients with acute leukemia, a suitably matched related donor is unavailable for approximately two-thirds of patients. Recently, umbilical cord blood from unrelated donors has been used as an alternative stem cell source for adult patients with hematological malignancies. Here, we updated the results of unrelated cord blood transplantation (CBT) after myeloablative conditioning for 69 adult patients with acute leukemia. Between August 1998 and April 2005, 69 adult patients with acute leukemia were treated with unrelated CBT at The Institute of Medical Science, University of Tokyo. Diagnoses at transplantation included de novo AML (n = 38), ALL (n = 16), and MDS-related secondary AML (n = 15). All patients received four fractionated 12 Gy total body irradiation and chemotherapy as myeloablative conditioning. 66 patients received standard cyclosporine (CyA) and methotrexate, and 3 patients received CyA only as a graft-versus-host disease (GVHD) prophylaxis. Among the patients the median age was 41 years (range, 18-55 years), the median weight was 55 kg (range, 36-76 kg) and the median number of cryopreserved nucleated cells was 2.50 × 107/kg (range, 1.16-5.29 × 107/kg). 65 patients had myeloid reconstitution and the median time to more than 0.5 × 109/L absolute neutrophil count was 21 days. A self-sustained platelet count more than 50 × 109/L was achieved in 59 patients at a median time of 39 days. Acute GVHD above grade II occurred in 39 of 65 evaluable patients and chronic GVHD occurred in 37 of 47 evaluable patients. Among 37 chronic GVHD patients, 12 patients were extensive type. 46 patients are alive and free of disease at between 126 and 2562 days after transplantation. With a median follow-up of 1259 days, the probability of disease-free survival at 3 years was 69.0%. These results suggest that adult acute leukemia patients without suitable related or unrelated bone marrow donors should be considered as candidates for CBT. Although allogeneic stem cell transplantation from a human leukocyte antigen (HLA)-identical related donor offers a potential cure for patients with acute leukemia, a suitably matched related donor is unavailable for approximately two-thirds of patients. Recently, umbilical cord blood from unrelated donors has been used as an alternative stem cell source for adult patients with hematological malignancies. Here, we updated the results of unrelated cord blood transplantation (CBT) after myeloablative conditioning for 69 adult patients with acute leukemia. Between August 1998 and April 2005, 69 adult patients with acute leukemia were treated with unrelated CBT at The Institute of Medical Science, University of Tokyo. Diagnoses at transplantation included de novo AML (n = 38), ALL (n = 16), and MDS-related secondary AML (n = 15). All patients received four fractionated 12 Gy total body irradiation and chemotherapy as myeloablative conditioning. 66 patients received standard cyclosporine (CyA) and methotrexate, and 3 patients received CyA only as a graft-versus-host disease (GVHD) prophylaxis. Among the patients the median age was 41 years (range, 18-55 years), the median weight was 55 kg (range, 36-76 kg) and the median number of cryopreserved nucleated cells was 2.50 × 107/kg (range, 1.16-5.29 × 107/kg). 65 patients had myeloid reconstitution and the median time to more than 0.5 × 109/L absolute neutrophil count was 21 days. A self-sustained platelet count more than 50 × 109/L was achieved in 59 patients at a median time of 39 days. Acute GVHD above grade II occurred in 39 of 65 evaluable patients and chronic GVHD occurred in 37 of 47 evaluable patients. Among 37 chronic GVHD patients, 12 patients were extensive type. 46 patients are alive and free of disease at between 126 and 2562 days after transplantation. With a median follow-up of 1259 days, the probability of disease-free survival at 3 years was 69.0%. These results suggest that adult acute leukemia patients without suitable related or unrelated bone marrow donors should be considered as candidates for CBT.