Cord-Blood Transplantation in Patients with Minimal Residual Disease

Abstract

Background: The majority of patients in need of a hematopoietic-cell transplant do not have a matched related donor. Data are needed to inform the choice among various alternative donor-cell sources.

Methods: In this retrospective analysis, we compared outcomes in 582 consecutive patients with acute leukemia or the myelodysplastic syndrome who received a first myeloablative hematopoietic-cell transplant from an unrelated cord-blood donor (140 patients), an HLA-matched unrelated donor (344), or an HLA-mismatched unrelated donor (98).

Results: The relative risks of death and relapse between the cord-blood group and the two other unrelated-donor groups appeared to vary according to the presence of minimal residual disease status before transplantation. Among patients with minimal residual disease, the risk of death was higher in the HLA-mismatched group than in the cord-blood group (hazard ratio, 2.92; 95% confidence interval [CI], 1.52 to 5.63; P=0.001); the risk was also higher in the HLA-matched group than in the cord-blood group but not significantly so (hazard ratio, 1.69; 95% CI, 0.94 to 3.02; P=0.08). Among patients without minimal residual disease, the hazard ratios were lower (hazard ratio in the HLA-mismatched group, 1.36; 95% CI, 0.76 to 2.46; P=0.30; hazard ratio in the HLA-matched group, 0.78; 95% CI, 0.48 to 1.28; P=0.33). The risk of relapse among patients with minimal residual disease was significantly higher in the two unrelated-donor groups than in the cord-blood group (hazard ratio in the HLA-mismatched group, 3.01; 95% CI, 1.22 to 7.38; P=0.02; hazard ratio in the HLA-matched group, 2.92; 95% CI, 1.34 to 6.35; P=0.007). Among patients without minimal residual disease, the magnitude of these associations was lower (hazard ratio in the HLA-mismatched group, 1.28; 95% CI, 0.51 to 3.25; P=0.60; hazard ratio in the HLA-matched group, 1.30; 95% CI, 0.65 to 2.58; P=0.46).

Conclusions: Our data suggest that among patients with pretransplantation minimal residual disease, the probability of overall survival after receipt of a transplant from a cord-blood donor was at least as favorable as that after receipt of a transplant from an HLA-matched unrelated donor and was significantly higher than the probability after receipt of a transplant from an HLA-mismatched unrelated donor. Furthermore, the probability of relapse was lower in the cord-blood group than in either of the other groups.

Figure 1. Unadjusted and Adjusted Estimates of Overall Survival and Relapse

Adjusted estimates are to be interpreted as the expected outcome if the HLA-matched and HLA-mismatched groups were the same, on average, as the cord-blood group with respect to disease severity, age of the patient, year of transplantation, and presence or absence of minimal residual disease. The hazard ratio for death in the HLA-matched group versus the cord-blood group was 1.12 (95% CI, 0.77 to 1.63; P = 0.57), and the hazard ratio in the HLA-mismatched group versus the cord-blood group was 1.91 (95% CI, 1.23 to 2.98; P = 0.004). The hazard ratio for relapse in the HLA-matched group versus the cord-blood group was 1.95 (95% CI, 1.16 to 3.27; P = 0.01), and the hazard ratio in the HLA-mismatched group versus the cord-blood group was 1.97 (95% CI, 1.04 to 3.73; P = 0.04).

Figure 2. Unadjusted and Adjusted Estimates of Overall Survival and Relapse among Patients with Minimal Residual Disease

Adjusted estimates are to be interpreted as the expected outcome if the HLA-matched and HLA-mismatched groups were the same, on average, as the cord-blood group with respect to disease severity, age of the patient, and year of transplantation. The hazard ratio for death in the HLA-matched group versus the cord-blood group was 1.69 (95% CI, 0.94 to 3.02; P = 0.08), and the hazard ratio in the HLA-mismatched group versus the cord-blood group was 2.92 (95% CI, 1.52 to 5.63; P = 0.001). The hazard ratio for relapse in the HLA-matched group versus the cord-blood group was 2.92 (95% CI, 1.34 to 6.35; P = 0.007), and the hazard ratio in the HLA-mismatched group versus the cord-blood group was 3.01 (95% CI, 1.22 to 7.38; P = 0.02). Data on minimal residual disease status were missing for 3 patients in the cord-blood group, for 13 in the HLA-matched group, and for 8 in the HLA-mismatched group.