General AML

Acute Leukemia/MDS patients with MRD receiving cord blood transplantation: higher OS and lower risk of relapse

Treatment of leukemia with transplantation of allogeneic bone marrow or stem cells from the peripheral blood is limited by the poor number of HLA-matched related donors. The purpose of this study was to conduct a retrospective analysis of outcomes in patients with Acute Lymphoid Leukemia (n=185), Acute Myeloid Leukemia (n=300) or Myelodysplastic Syndrome (n=97), who either received a transplant form a cord-blood donor (n=140), a HLA-matched unrelated donor (n=344) or from a HLA-mismatched unrelated donor (n=98).

Dr Filippo Milano and his colleagues from the Fred Hutchinson Cancer Research Centre, Seattle, USA, also analyzed if there was a difference in the relative risk of deaths and relapse between the cord-blood group and the other two unrelated donor groups with respect to numerous outcomes according to presence or absence of minimal residual disease (MRD) before transplantation. They published their data in the New England Journal of Medicine on the 8th of September 2016.

The key findings of the study are as follows:
  • The percentage of patients with MRD at the time of transplantation was similar in the three groups: 33% (45/137) in the cord-blood group, 31% (104/331) in the HLA-matched group and 39% (35/90) in the HLA-mismatched group
  • The survival rate was higher after receipt of a transplant from a cord-blood donor compared to receipt from a HLA-mismatched donor (HR = 1.91; 95% CI, 1.23 to 2.98; P = 0.004) although there was no difference between receipt from a cord-blood or a HLA-matched donor (HR = 1.12; 95% CI, 0.77 to 1.63; P = 0.57)
  • The difference in the outcome between the cord-blood group and the HLA-matched group varied significantly according to MRD status (P = 0.04 for interaction) whereas there was only a trend toward significance in the outcome between the HLA-mismatched group and the cord-blood group according to MRD status, P = 0.08
  • Among patients without MRD, the risk of death was lower in the HLA-matched group than in the cord-blood group, but the difference was not significant. In the same MRD negative patients, the risk of relapse was not significantly higher in the cord-blood group compared to the two other groups (HR = 1; HR = 1.30 for the HLA-matched group, P = 0.46 and HR = 1.28 for the HLA-mismatched group, P = 0.60).  On the contrary, among patients with MRD, the risk of relapse was significantly lower in the cord-blood group compared to the two other groups (HR = 1; HR = 2.92 for the HLA-matched group, P = 0.007 and HR = 3.01 for the HLA-mismatched group, P = 0.02).

Conclusions


Even though the data analyzed here focuses on a cohort of patients based on clinical priority and non-randomization, it does provide evidence and guidance regarding difficult donor choices in circumstances where a HLA-identical sibling is not available. Future studies based on randomization would determine the differences between cord-blood and unrelated-donor transplantations.

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 pre-transplantation 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.

References
  1. Milano F. et al. Cord-Blood Transplantation in Patients with Minimal Residual Disease. N Engl J Med. 2016 Sep 8; 375(10):944-953.