Unrelated Donor Umbilical Cord Blood Transplantation (UD-UCBT) for Adult Patients with High-Risk Acute Lymphoblastic Leukemia (ALL).

BACKGROUND: Adult patients with high-risk ALL can benefit from allogeneic stem cell transplantation but most lack a suitable sibling or unrelated adult donor. Umbilical cord blood has emerged as an alternative source for stem cell transplantation.

OBJECTIVES: The aim of the present study was to evaluate toxicity and efficacy of UD-UCBT for the treatment of high-risk ALL in adults as well as to identify by multivariate analysis factors affecting transplant outcome.

PATIENTS AND METHODS: Thirty-seven consecutive patients (23 males, 14 females) with median age 26 yr (range, 15–47) who underwent UD-UCBT at a single institution from 1999 until 2006 were analyzed. Primary high-risk feature was Philadelphia-positive ALL (12), MLL rearrangement (3), primary refractory disease (3), salvage treatment for patients in second complete remission (CR2, 4) or beyond CR2 (6), and slow response to initial therapy or 2 cycles to achieve CR (9). Conditioning regimen consisted of thiotepa, busulfan (oral, 13; IV, 24), cyclophosphamide (24) or fludarabine (13), and anti-thimocyte globulin. Cyclosporine and prednisone were used for graft-versus-host disease (GVHD) prophylaxis. Most patients (95%) received an HLA-mismatched cord blood unit with 1 (35%) or 2 (60%) HLA disparities. At infusion, the median number of nucleated cells and CD34+ cells was 2.4 × 10⁷/kg and 1.3 × 10⁵/kg, respectively.

RESULTS: Cumulative incidence (CI) of myeloid and platelet engraftment was 92% and 76% at a median time of 21 and 63 days respectively. CI of GVHD acute grades II-IV, III-IV and chronic extensive was 29%, 19% and 19% respectively. Transplant-related mortality at 180 days was 29% and was significantly increased in patients developing severe acute GVHD (96% vs 19%; p < 0.001). With a median follow-up of 23 months (range, 7–88), CI of relapse was 34% at 3 years and was higher in patients beyond CR1 (63% vs 28%; p < 0.001). 3-year event-free survival (EFS) and overall survival (OS) were 33% and 37%, respectively. Patients in CR1/2 had better EFS (41% vs 14%; p = 0.04) and OS (50% vs 14%; p = 0.04) while those who developed severe acute GVHD had a worse EFS (42% vs 0%; p = 0.004) and OS (49% vs 0%; p = 0.004).

CONCLUSIONS: These results show that UD-CBT is a curative alternative for a significant number of patients with high-risk ALL. This option should be offered to patients early in the course of their disease to improve outcomes.