Umbilical Cord Blood Transplant Treats Children With Genetic Disorders, Trial Finds

Joana Carvalho, PhD avatar

by Joana Carvalho, PhD |

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Stem Cell Transplant, Gene Therapy, Improved Quality of Life

An umbilical cord blood transplant, coupled with a reduced intensity conditioning (RIC) regimen, can safely and effectively treat children with genetic disorders that include sickle cell disease (SCD) and thalassemia, data from a Phase 2 trial show.

These findings are detailed in the study, “Reduced-intensity single-unit unrelated cord blood transplant with optional immune boost for nonmalignant disorders,” published in the journal Blood Advances.

An umbilical cord blood transplant, known as UCBT, is a procedure in which blood isolated from the umbilical cord and placenta of healthy babies at birth — a readily available source of stem cells— is infused to a patient with the goal of resetting and restoring the production of healthy blood cells.

Compared to a blood marrow transplant, UCBT is more easily accessible and less likely to lead to rejection or other transplant complications when a donor and recipient are not a perfect match.

These features make UCBT particularly suitable as a universal treatment for children with non-cancerous genetic disorders, bringing another alternative to more specific therapies directed to each disorder.

“There has been a lot of emphasis placed on cool new technologies that might address these diseases, but — even if they prove effective — those aren’t available to most centers,” Paul Szabolcs, MD, division director of bone marrow transplantation and cellular therapies at UPMC Children’s Hospital of Pittsburgh, and the study’s senior author, said in a press release.

“The regimen we developed is more robust, readily applicable and will remain significantly less expensive,” Szabolcs said.

This regimen consisted not only on UCBT itself, but also a new conditioning regimen that involved a combination of low-dose chemotherapy and immunosuppressant treatments. This regimen is given to patients prior to the transplant to reduce a risk of rejection.

Rather than administer all umbilical cord blood at once, the investigators also reserved 5% to be given at a later stage. This was done to spur a patient’s immune system into action as fast as possible.

The safety and efficacy of this new regimen was tested in a Phase 2 trial (NCT01962415), the largest of its kind to date, that enrolled 44 children (median age, 1.7; maximum age, 16) with different metabolic, immune-related, or blood disorders.

The study, which also includes adults up to age 55 and is set to end in November 2022, is still recruiting patients at its single UMPC site. More information is available here.

Transplanted cells were successfully implanted in all children at a median of 15 days following the transplant. One year later, more than 90% of blood cells in most of these children were derived from the donor, confirming the procedure’s effectiveness. The transplant failed in one child, the researchers reported.

Complications following the umbilical cord blood infusion were relatively mild. The incidence of graft-versus-host disease (GVHD) — a potential life-threatening condition that occurs when the recipient’s immune system perceives the donor’s cells as a threat — was 27% at six months. No child developed severe GVHD.

Nearly all children were alive at one (95%) and five years (85%) post-transplant. High survival rates (around 90%) were also observed in a subgroup of children with rare childhood disorders known as leukodystrophies, where three-year survival rates typically do not surpass 60% even with treatment.

“This RIC transplant regimen using single-unit UCB graft resulted in outstanding survival and remarkably low rates of graft failure,” the investigators wrote.

In a subgroup of 30 children with metabolic disorders caused by the lack of specific enzymes, the transplant not only restored the production of the missing enzymes after one year, but also halted the progression of neurological decline.

“We designed an approach now proven to be efficacious for at least 20 diseases. And we believe it might be effective for many, many more,” Szabolcs said.

Since submitting their study for publication, Szabolcs and his colleagues report having successfully used this treatment regimen in adults and in children with other diseases.