Cord Blood Transplant: In Children, One Will Do

Alexander M. Castellino, PhD

October 29, 2014

It may seem intuitive that, in stem cell transplantation, two units of cord blood may bestow significantly better outcomes than one unit of cord blood. But at least in children, that may not be the case: the outcomes were similar after both.

That is the conclusion from the Bone and Marrow Transplant Clinical Trials Network study that was published in the October 29 issue of the New England Journal of Medicine.

Medscape Medical News reported the initial presentation of these data from the 2012 annual meeting of the American Society of Hematology.

"We found that among children and adolescents with hematologic cancer, survival rates were similar after single-unit and double-unit cord-blood transplantation," concluded principal and corresponding author John E. Wagner, MD, a pediatric hematologist oncologist at the University of Minnesota Medical School, in Minneapolis.

"While there is no advantage of two vs one unit of cord transplant in children, the study does not answer this question in adults," Karen K. Ballen, MD, director of the Leukemia Program at the Massachusetts General Hospital and professor of Medicine at the Harvard Medical School told Medscape Medical News. She was not involved in the study.

Open-Label Multicenter Study

The study reported by Dr Wagner and colleagues was an open-label, phase 3 study that randomly assigned children, adolescents, and young adults aged 1 to 21 years to receive double-unit cord- blood transplant (n = 111) or single-unit cord-blood transplant (n = 113).

Cases involving several hematologic malignancies were included in the study, including high-risk acute leukemia, chronic myeloid leukemia, or myelodysplastic syndrome.

Median age at transplantation was 9.9 years for double-unit recipients and 10.4 years for single-unit recipients. Correspondingly, median weight was 37 kg and 35.7 kg, respectively. Approximately 74% of the children were white, and 10% were black.

Cord blood was HLA-matched both to the patient and, when two units were used, to each other to at least 4 of 6 different loci.

The first unit of cord blood was required to contain at least 2.5 x 107 nucleated cells per kg of the patient's body weight, and the second unit, at least 1.5 x 107 nucleated cells per kg of body weight.

More than 10 days before transplantation, all patients received a conditioning regimen of fludarabine, total body irradiation, and cyclophosphamide to kill all leukemia cells and to suppress the patient's immune system.

In addition, patients received prophylaxis for graft-vs-host disease (GVHD).

Two Units Are Not Better Than One Unit

The two treatment groups were well balanced for sex, age, status of cytomegalovirus, disease type, and status at transplantation.

Overall survival at the end of 1 year, the primary endpoint of the study, was 65% for double-unit recipients and 73% for single-unit recipients. Hazard ratio for mortality was 1.34 (95% confidence interval: 0.86 - 2.09; P = .20) for double-unit vs single-unit recipients.

One-year disease-free survival was also not significantly different: 64% vs 70% for double- and single-unit recipients, respectively.

Neutrophil recovery — a measure for transplant success — was similar across the two groups: 88% vs 89% for double- and single-unit recipients, respectively.

Acute and chronic GVHD, treatment-related infections, relapse, and mortality were not significantly different between groups.

Dr Wagner and colleagues report that in subgroup analyses, race, sex, age, and HLA match had no effect on survival. However, an exploratory analysis indicated that "a diagnosis of acute myeloid leukemia, non-white race, and a better HLA-match score were associated with a lower of disease-free survival after cord-blood transplantation."

"The potential beneficial effect of greater HLA mismatch is provocative and merits further examination in a larger population," the authors write in their discussion.

Differences in GVHD

Platelet recovery was significantly higher (76% vs 65%; P = .04) and occurred sooner (58 days vs 84 days) for patients receiving one unit than for those receiving two units of cord blood.

Although incidence of GVHD grade II-IV was similar across the two groups, double-unit transplantation was associated with a higher incidence of grade III and IV GVHD (23% vs 13%; P = .02).

Perspectives in Cord Blood Transplantation

Dr Ballen provided Medscape Medical News a perspective on cord blood transplantation, a source of hematopoietic stem cells for patients across multiple hematologic malignancies, which has been used for more than 25 years.

"Transplantation is curative for hematologic malignancies and for several cancers. However, most patients do not have a donor in the family to facilitate this process," Dr Ballen said.

Typically, for patients without a family donor, established registries provide appropriate donors for hematopoietic stem cells. Cord blood transplant is especially important for those who cannot obtain stem cell match from the registries — approximately 20% of non-white patients.

This randomized study says that for children who need stem cell transplantation and who have an adequate single unit [based on nucleated cells], two units of cord blood do not provide any additional benefit compared with one unit. Indeed, there is no need for additional resource utilization, Dr Ballen said.

Regardless of whether children received one unit or two units of cord blood, engraftment and survival outcomes were better in this study compared with the National Heart, Lung, and Blood Institute–sponsored COBLT study, which had a different conditioning regimen.

However, the study does not broaden the discussion of the applicability of double-unit cord blood transplantation for adults.

The study was funded by grants from the National Heart, Lung, and Blood Institute and the National Cancer Institute. The authors and Dr Ballen report no relevant financial relationships.

New Engl J Med. 2014;371:1685-1694.

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