New cell products can improve cord blood transplant outcomes

Hematopoietic stem cell transplant is a powerful treatment option for patients with blood cancers. Despite the curative potential for hematopoietic stem cell transplant, not every patient who needs a transplant is able to receive one. One common problem facing patients who need transplants is the lack of an HLA-matched donor. HLA matching can improve the chances of a successful transplant and help prevent severe complications like graft-versus-host disease. Many patients find a related HLA-matched donor in their family or an unrelated donor from registries like the National Marrow Donor Program. However, some patients, especially those from racial or ethnic minority backgrounds, are unable to find an HLA-matched donor for their transplant.

To help patients without a matched donor, doctors developed the umbilical cord blood transplant in 1988. If parents choose to donate their baby’s cord blood, doctors can preserve the blood left in the umbilical cord born by freezing it. The cord blood is then stored at a blood bank. Because cord blood cells are immunologically naïve, they do not react as strongly to a recipient’s cells, so cord blood cells do not need to be a complete HLA match for a transplant patient to receive them. While cord blood transplant expands who can receive a stem cell transplant, there are unique limitations to this strategy. Cord blood does not have as many stem cells as a more traditional matched donation from bone marrow, and this can lead to delayed engraftment and a longer immune recovery time for patients. Sometimes, doctors will transplant two cord blood units to speed up engraftment and recovery, but this approach is more expensive, increases the risk of severe graft-versus-host disease, and does not offer a consistent survival advantage for patients.

Deverra Therapeutics developed a hematopoietic progenitor cell product called dilanubicel to help support cord blood transplant recipients during engraftment and recovery. Dilanubicel is made by expanding cord blood cells in a dish to generate immature blood cells that are not capable of engraftment, and it is infused alongside the donor cord blood. Dilanubicel supports transplant recipients by quickly expanding into mature blood cells that only persist for a short time. This helps the transplanted cord blood cells establish a new, healthy immune system in the patient in the long-term. Because dilanubicel is depleted of T cells prior to transplant, it has minimal risk of causing severe complications like graft-versus-host disease. Prior work has shown that dilanubicel is safe for patients and supports blood system recovery after chemotherapy, but its potential as an adjuvant for transplants was unclear. A recent phase II clinical trial from Dr. Filippo Milano and colleagues in the Translational Sciences and Therapeutics Division investigated how dilanubicel impacted outcomes for cord blood transplant recipients.

Twenty-eight participants with different types of blood cancer received cord blood transplants supplemented with dilanubicel. After follow-up, 27 patients were alive and in remission. One patient died due to complications unrelated to the transplant. Over the course of the study, only one patient relapsed, but he achieved remission following additional treatment. No patients experienced infusion-related toxicities. Three quarters of patients experienced low-grade acute graft-versus-host disease, but, strikingly, no patients had severe acute or chronic graft-versus-host disease. In contrast, 26% of transplant recipients who received cord blood only developed high-grade graft-versus-host disease, and 21% developed chronic graft-versus-host disease.

The team also quantified hematopoietic recovery in patients that received dilanubicel with their cord blood transplant. A spike in the number of lymphocytes, or immune cells, after transplant generally predicts more favorable outcomes for recipients. The researchers saw that all the patients they analyzed had a transient lymphocyte spike roughly 11 days after their transplants. Patients from another cord blood transplant cohort who did not receive dilanubicel did not have a lymphocyte spike, suggesting this is specific to dilanubicel treatment. To tease apart the precise immune cells contributing to the lymphocyte spike, they performed single-cell RNA sequencing for 3 dilanubicel recipients and 3 controls. They saw that patients who received dilanubicel had significantly more CD8+ T cells and fewer monocytes compared to untreated controls. Frequencies of natural killer and CD4+ T cells were similar between the groups.

Because dilanubicel is depleted of T cells during manufacturing, the quick expansion of CD8+ T cells in patients must be coming from the healthy donor cord blood unit. This suggests that dilanubicel indeed supports engraftment and immune recovery in recipients. While the exact mechanism underlying this phenomenon is unclear, the authors suggest that dilanubicel may create a primed immune environment through short-term activation of healthy donor T cells. In the future, the researchers hope that more trials will be done to understand how dilanubicel produces these effects and investigate whether it could be used as an adjuvant for other types of hematopoietic stem cell transplants.

This work was supported by funding and materials from the Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation, the George & Fay Young Foundation, Fred Hutchinson Cancer Center, and Deverra Therapeutics.

Fred Hutch/University of Washington/Seattle Children’s Cancer Consortium Members Drs. Filippo Milano, Ann Dahlberg, Francesco Mazziotta, Brandon Hadland, Aude Chapuis, and Colleen Delaney contributed to this work.

Milano F, Dahlberg A, Pedersen J, Roberts L, Azure A, Martin L, Mazziotta F, Hadland B, Chapuis AG, Delaney C. 2026. Safety and Clinical Outcomes of Pooled Donor, Nonengrafting Expanded Progenitor Cells in Single-Unit Cord Blood Transplantation. J Clin Oncol. 2026 Apr 27:JCO2502510. doi: 10.1200/JCO-25-02510.