Unrelated Donor Umbilical Cord Blood Transplantation (UD-UCBT) for Adult Patients with High-Risk Acute Myeloid Leukemia (AML)

BACKGROUND: Adult patients with high-risk AML 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 AML in adults as well as to identify, by multivariate analysis, factors affecting transplant outcome.

PATIENTS AND METHODS: Forty-four consecutive patients (27 males, 17 females) with a median age of 34 yr (range, 16–52) who underwent UD-UCBT at Hospital Universitario La Fe from 2000 until 2007 were analyzed. Primary high-risk feature was high risk cytogenetics (13), therapy-related AML (3) and two or more cycles to achieve first complete remission (CR1, 10) for patients transplanted in CR1 and salvage treatment for patients in second complete remission (CR2, 6) or more advanced stage of the disease (12). Five patients had failed a previous autologous stem cells transplant (ASCT). Conditioning regimen consisted of thiotepa, busulfan (oral, 8; IV, 36), cyclophosphamide (16) or fludarabine (28), and anti-thymocyte globulin. Cyclosporine and prednisone (37) or cyclosporine and mycophenolate mofetil (7) were used for graft-versus-host disease (GVHD) prophylaxis. Most patients (93%) received an HLA-mismatched cord blood unit with 1 (43%) or 2 (50%) disparities. The median number of total nucleated cells (TNC) and CD34+ cells infused was 2 ×10⁷/kg (range, 1–4.4) and 1.2 ×10⁵/kg (range, 0.1–6), respectively.

RESULTS: Cumulative incidence (CI) of myeloid and platelet engraftment was 98% and 72% at a median time of 20 and 54 days respectively. Higher CFU-GM counts at infusion accelerated neutrophil recovery and higher CD34+ cell dose at infusion as well as being in first complete remission (CR1) improved platelet engraftment. CI of acute GVHD grades II–IV and III–IV was 20% and 9%, respectively. CI of chronic and chronic extensive GVHD was 47% and 21%, respectively. CI of non-relapse mortality at 2 years was 38% and was significantly increased in patients transplanted beyond CR1 (53% vs 29%; p = 0.01). With a median follow-up of 19 months (range, 7–75), CI of relapse was 20% at 2 years and was higher in patients beyond CR1 (35% vs 18%; p = 0.02) and in patients receiving a lower TNC dose (39% vs 9%; p = 0.02). Event-free survival (EFS) at 2 years was 42% and was significantly higher for patients in CR1 (53% vs 19%; p < 0.01).

CONCLUSIONS: These results show that UD-CBT is a curative alternative for a significant number of patients with high-risk AML. This option should be offered to patients early in the course of their disease to improve outcomes. Apart from disease status, cord blood cell dose affected engraftment and could also influence relapse incidence.