Allogeneic stem cell transplantation with omidubicel in sickle cell disease

Abstract

Many patients with sickle cell disease (SCD) do not have HLA-matched related donors for hematopoietic stem cell transplantation (HSCT). Unrelated cord blood (UCB) is an alternative graft option but is historically associated with high graft failure rates, with inadequate cell dose a major limitation. Omidubicel is a nicotinamide-based, ex vivo-expanded UCB product associated with rapid engraftment in adults with hematologic malignancies. We hypothesized that increasing the UCB cell dose with this strategy would lead to improved engraftment in pediatric patients undergoing myeloablative HSCT for SCD. We report the outcomes of a phase 1/2 study in 13 patients with severe SCD who received omidubicel in combination with an unmanipulated UCB graft and 3 who received a single omidubicel graft. Grafts were minimally matched with patients at 4 of 6 HLA alleles. Median age at transplant was 13 years. A median CD34+ expansion of ∼80-fold was observed in omidubicel and led to rapid neutrophil engraftment (median, 7 days). Long-term engraftment was derived from the unmanipulated graft in most of the double cord blood recipients. Two of the 3 single omidubicel recipients also had sustained engraftment. Incidence of acute graft-versus-host disease (GVHD) was high, but resolved in all surviving patients. Event-free survival in the double cord group was 85% (median follow-up 4 years). All 3 patients in the single cord group were alive at 1 year after transplantation. Ex vivo expansion of UCB with omidubicel supports engraftment in patients with SCD. This approach to decreasing the incidence of GVHD should be optimized for general use in patients with SCD. This study was registered at www.clinicaltrials.gov as #NCT01590628.

Conflict of interest statement

Conflict-of-interest disclosure: E.G. and A.S. are employees of Gamida Cell. The remaining authors declare no competing financial interests.

© 2021 by The American Society of Hematology.

Figures

Graphical abstract

Figure 1.

Graft characteristics. TNC dose and CD34+ cell dose for unmanipulated UCB units and before and after ex vivo expansion of the CBU for omidubicel. Precryopreservation values represent cell content as reported by the cord blood bank. (A) DC cohort (n = 13), median (range). (B) SC cohort (n = 3), individual patient results. Cryo, cryopreservation; UM, unmanipulated cord.

Figure 2.

Chimerism: whole blood. Percentage of whole-blood chimerism from omidubicel (red) and unmanipulated UCB graft (blue) are shown in individual patients in the DC cohort (n = 13).

Figure 3.

Chimerism: CD3+fraction. Percentage of CD3+ (T-cell) peripheral blood chimerism from omidubicel (red) and unmanipulated UCB graft (blue) are shown in individual patients in the DC cohort (n = 13).

Figure 4.

Chimerism: myeloid fraction. Percentage of myeloid peripheral blood chimerism from omidubicel (red) and unmanipulated UCB graft (blue) are shown in individual patients in the DC cohort (n = 13).

Figure 5.

Immune reconstitution. Cell counts (cells per microliter) for CD3, CD4, CD8, CD45RA+62L+, CD4+CD25+, CD19, and CD16+56+ cells at 100, 180, 365, and 730 days after transplantation in a subset of patients in the DC cohort (n = 9).