Cord Blood HSCT Better for High-Risk Leukemia Patients

Alexander Castellino, PhD

September 08, 2016

For leukemia patients who are to undergo hematopoetic stem cell transplant (HSCT), the use of cord blood from an unrelated source appears to yield better outcomes than use of either bone marrow or peripheral blood.

A retrospective analysis has found that for such patients, the probability of overall survival after a cord-blood transplant was at least as favorable as that after receipt of a transplant from an HLA-matched unrelated donor and was significantly higher than after receipt of a transplant from an HLA-mismatched unrelated donor. In addition, the risk for relapse was lower for patients receiving cord blood.

The findings were reported by researchers from the Fred Hutchinson Cancer Center in an article published online September 8 in the New England Journal of Medicine.

"Patients with detectable amounts of cancer cells in their blood could benefit from choosing cord blood as the source of stem cells for their transplant over a traditional transplant," lead author Filippo Milano, MD, PhD, said in a Fred Hutchinson Cancer Center press release.

This patient population – leukemia patients with minimal residual disease in whom cancer cells remain following chemotherapy before transplant – account for about one third of leukemia patients who undergo HSCT.

Such patients generally have "very dismal outcomes," Dr Milano commented, but this study showed that those who received a cord blood transplant "had good outcomes with low relapse rate" compared with patients who received stem cells from an unrelated adult donor.

For the two thirds of patients with no minimal residual disease following chemotherapy, cord blood and traditional transplants yielded very similar outcomes.

Details of the Study

For this study, the researchers analyzed outcomes of 582 consecutive patients with acute leukemia or myelodysplastic syndrome. The review period was from 2014 to 2006.

The team found that 344 patients received a transplant from an HLA-matched unrelated donor (bone marrow transplant: 107 patients; peripheral blood transplant: 237 patients); 98 patients received a transplant from an HLA-mismatched unrelated donor (bone marrow transplant: 28 patients; peripheral blood transplant: 70 patients); and 140 patients received cord blood.

The overall results showed that at 4 years, survival rates were 71% for the cord-blood group, 63% for the HLA-matched group, and 49% for the HLA-mismatched group.

Compared with patients receiving cord blood, risk for death was significantly higher in recipients of HLA-mismatched transplants (hazard ratio [HR], 1.91; P = .004) and was similar in recipients of HLA-matched transplants (HR, 1.12; P = .57).

However, when the data were analyzed on the basis of the presence or absence of minimal residual disease, the results differed.

Patients with minimal residual disease were similar across the three groups: 33% in the cord-blood group; 31% in the HLA-matched group; and 39% in the HLA-mismatched group.

For patients without minimal residual disease, risk for death or relapse was not significant for recipients of HLA-matched or HLA-mismatched transplant recipients compared with cord blood recipients.

But for patients with minimal residual disease, risk for death was highest in patients receiving HLA-mismatched transplants (HR, 2.92 vs cord-blood group; P = .001) but less so and not significant for patients receiving HLA-matched transplants (HR, 1.69 vs cord-blood group; P = .08).

In this same subgroup of patients, risk for relapse was significantly higher in HLA-mismatched and HLA-matched transplant recipients (HR for HLA-matched group: 2.92; P = .007; HR for HLA-mismatched group: 3.01; P = .02).

Grade 3 or 4 graft-vs-host disease was numerically, but not significantly, higher in recipients of HLA-mismatched transplants (26% vs 18% and 14% for the cord-blood group and the HLA-matched group, respectively).

In their discussion, the investigators concede that "a randomized trial is the only way to assess definitively the differences between cord-blood and unrelated donor transplantation.

"Given the lack of such a trial, however, studies such as this are one means of providing guidance regarding difficult donor choices in situations in which an HLA-identical sibling is not available," they add.

They point out that because cord blood provides for greater HLA disparity, suitable donors can be found for almost all patients, regardless of racial and ethnic differences. This may be most appropriate for nonwhite racial and ethnic minorities — patients for whom it is difficult to find appropriate donors.

"Everyone has a cord blood donor," said Colleen Delaney, MD, coauthor of the article and founder of the cord blood program at Fred Hutchinson. "This brings home the point that cord blood shouldn't be called an alternative donor. The outcomes are the same as a conventional donor," she said in a statement. "This paper shows that if you've got high-risk disease and are at high risk for relapse post transplant, transplant with a cord blood donor may be the best option."

In the article, the research team cautions that the number of patients in each group analyzed was small. This, in addition to the analyses undertaken and the retrospective nature of the study, "requires that our conclusions be made both with caution and with a call for further examination in the future."

Dr Milano and Dr Delaney have received funding for clinical trials from Medac GmbH. Several coauthors have disclosed financial relationships with industry, as listed in the original article.

N Engl J Med. 2016;375:944-53. Abstract


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