An off-the-shelf progenitor cell therapy added to cord blood transplantation delivered rapid engraftment, no severe GVHD and 96% overall survival in a phase 2 trial.
A cryopreserved progenitor cell product derived from pooled cord blood donors may help overcome one of the biggest barriers to cord blood transplantation – delayed engraftment and high rates of severe graft-versus-host disease.
In a phase 2 trial published in the Journal of Clinical Oncology, US researchers reported that adding dilanubicel to single-unit cord blood transplantation produced rapid haematopoietic recovery with no cases of grade 3-4 acute GVHD or chronic GVHD.
The study enrolled 28 patients with haematologic malignancies between 2022 and 2025, most of whom had acute leukaemias and high-risk disease features.
Patients received a myeloablative conditioning regimen followed by infusion of a matched single cord blood unit and then dilanubicel, an off-the-shelf, non-HLA-matched expanded progenitor cell product generated from pooled donor cord blood CD34-positive cells.
All patients achieved neutrophil engraftment, with a median time of 18 days, while platelet recovery occurred at a median of 31 days. No primary or secondary graft failures were observed.
At a median follow-up of 1.4 years, 27 of 28 patients were alive and disease-free.
“When evaluated alongside a contemporaneous institutional cohort receiving standard single- or double-unit CBT, patients treated with dilanubicel demonstrated faster hematopoietic recovery and a markedly lower incidence of severe acute GVHD,” the researchers wrote.
The absence of severe GVHD stood out against outcomes in a contemporaneous institutional cohort of 24 patients undergoing standard single- or double-unit cord blood transplantation.
In that control group, grade 3-4 acute GVHD occurred in 26% of patients and chronic GVHD in 21%, while no such cases occurred in the dilanubicel group.
Patients receiving dilanubicel also experienced significantly faster neutrophil and platelet recovery, alongside improved overall and disease-free survival compared with standard cord blood transplantation. Median neutrophil recovery was shortened from 22 to 18 days, while platelet engraftment improved from 37 to 31 days.
The investigators observed an unusual transient lymphocyte expansion occurring around days nine to 11 after transplant, preceding neutrophil recovery. Chimerism studies showed the lymphocyte spike originated entirely from the primary cord blood graft rather than the dilanubicel product itself.
Single-cell RNA sequencing suggested this response was dominated by activated CD8-positive T cells with a polyclonal cytotoxic profile, raising the possibility that transient immune activation may enhance graft-versus-leukaemia effects without triggering severe GVHD.
The researchers said that dilanubicel may act as a “biologic adjuvant”, briefly stimulating donor immune responses through HLA disparity without persisting long-term or contributing to chronic alloreactivity.
Cord blood transplantation remains an important option for patients lacking matched donors, particularly those from ethnically diverse backgrounds, but delayed immune recovery and transplant-related toxicity have limited uptake.
Double-unit cord blood transplantation has often been used to boost cell dose in adults, although this strategy increases cost and GVHD risk without consistent survival benefits.
Unlike other expanded cord blood products requiring patient-specific manufacturing, dilanubicel is cryopreserved and immediately available, potentially avoiding transplant delays.
The authors cautioned that the trial was small, single-arm and conducted at a single centre, limiting definitive comparisons with other graft sources. Still, they said the combination of rapid engraftment, low relapse rates and absence of severe GVHD justified further multicentre evaluation.
“The ability to harness early immune activation without inducing chronic immunopathology represents a key advantage of this platform,” they concluded.
“Importantly, future applications should consider that the observed early lymphocyte expansion may reflect intrinsic properties of CB T cells and, even if not unique to CB, may require a T-cell–replete graft in which early immune activation is not attenuated by post-transplant CY.
“Accordingly, prospective multicentre studies are planned to evaluate dilanubicel as an adjunct cellular therapy across diverse allogeneic HCT platforms, including matched and haploidentical donors, 16 with integrated correlative analyses to define immunologic mechanisms, assess generalizability beyond CBT, and determine its potential to reduce relapse without increasing GVHD.”
