Umbilical cord blood transplantation after nonmyeloablative conditioning: impact on transplantation outcomes in 110 adults with hematologic disease

Abstract

We evaluated the efficacy of umbilical cord blood (UCB) in the setting of a nonmyeloablative regimen consisting of fludarabine (200 mg/m2), cyclophosphamide (50 mg/kg), and a single fraction of total body irradiation (200 cGy) with cyclosporine and mycophenolate mofetil for posttransplantation immunoprophylaxis. The target cell dose for the UCB graft was 3.0 x 10(7) nucleated cells/kg, resulting in the selection of a second partially human leukocyte antigen-matched UCB unit in 85%. One hundred ten patients with hematologic disease were enrolled. Neutrophil recovery was achieved in 92% at a median of 12 days. Incidences of grades III and IV acute and chronic graft-versus-host disease (GVHD) were 22% and 23%, respectively. Transplantation-related mortality was 26% at 3 years. Survival and event-free survival (EFS) at 3 years were 45% and 38%, respectively. Favorable risk factors for survival were absence of high-risk clinical features (Karnofsky 50-60, serious organ dysfunction, recent fungal infection, P < .01) and absence of severe GVHD (P = .04), and favorable risk factors for EFS were absence of high-risk clinical features (P < .01) and use of 2 UCB units (P = .07). These findings support the use of UCB after a nonmyeloablative conditioning as a strategy for extending the availability of transplantation therapy, particularly for older patients.

Figures

Figure 1

Cumulative incidence of neutrophil recovery by day 42 and unsupported platelet recovery greater than 50 × 109/L at 6 months after nonmyeloablative umbilical cord blood transplantation. (A) Neutrophil recovery. (B) Unsupported platelet recovery.

Figure 2

Bone marrow chimerism 21, 100, 180, and 365 days after nonmyeloablative umbilical cord blood transplantation. The solid horizontal line indicates the median chimerism; ◇, patients with sustained donor engraftment; and ▴, patients who developed graft failure.

Figure 3

Cumulative incidence of grades II-IV (––) and grades III and IV (----) acute GVHD and 3-year treatment-related mortality after nonmyeloablative umbilical cord blood transplantation. (A) Incidences of GVHD. (B) Incidence of 3-year treatment-related mortality.

Figure 4

Cumulative proportion of 3-year event-free survival and overall survival for patients receiving either 1 (—) or 2 (---) UCB unit transplantation after a nonmyeloablative conditioning regimen. (A) Event-free survival. (B) Overall survival.