Intrabone transplant of a single unwashed umbilical cord blood unit with ATG-free and sirolimus-based GvHD prophylaxis: fast immune-reconstitution and long-term disease control in 30 patients with high-risk diseases.

INTRO: Several strategies have been explored with the attempt of improving safety and feasibility of umbilical cord blood transplant (UCBT) in adults.

AIM: The aim of this retrospective analysis was to examine the safety and efficacy of intrabone transplant of a single unwashed cord blood unit in an ATG-free, sirolimus-based graft-versus-host prophylaxis platform.

METHODS: We collected data of all consecutive UCBT infused intrabone and unwashed at San Raffaele Hospital in Milan between 2012 and 2021.

RESULTS: Thirty-one consecutive UCBT were identified. All but 3 units had a high-resolution HLA typing on 8 loci at time of selection. At cryopreservation, the median number of CD34+ cells and total nucleated cells (TNCs) were 1 × 105 /kg (0.6-12.0) and 2.8 × 107 /kg (1.48-5.6), respectively. Eighty seven percent of patients received myeloablative conditioning; seventy seven percent of patients were transplanted for acute myeloid leukemia. Median follow-up among survivors was 38.2 months (range 10.4-123.6). No adverse events were related to the intrabone infusion at bedside under short-conscious peri-procedural sedation and to the no wash technique. After thawing, CD34+ and TNCs were 0.8 × 105 /kg (0.1-2.3) and 1.42 × 107 /kg (0.69-3.2) respectively. Median time to engraftment was 27 and 53 days for neutrophils and platelets, respectively; one patient rejected the transplant and was subsequently rescued with a salvage transplant. Median time to CD3+ above 100/μL was 30 days. 100-day CI of III-IV aGvHD was 12.9% (95%CI 4-27.3%), 2-year CI of moderate-to-severe chronic GvHD was 11.8% (95% CI 2.7-28.3%); at 2-year, OS was 52.7% (95%CI 33-69%), relapse incidence was 30.7% (95% CI 13.7-49.6%) and TRM of 29% (95%CI 14.3-45.6%). In univariate analysis CD34+ infused counts did not impact on transplant outcomes. In patients transplanted in first complete remission, relapse rate was 13% with an OS above 90% at 2 years.

CONCLUSIONS: Intrabone infusion of single CB unit was feasible, with no adverse reactions related to the no wash/intrabone infusion. We documented a low incidence of chronic GVHD and disease relapse with a fast immune-reconstitution.