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Results from a Prospective Phase II Clinical Study: High Vs Medium-Intensity Regimens in Patients Undergoing Cord Blood Transplantation

Year: 2025

Type: article

Abstract: Introduction We prospectively analyzed outcomes for UCB transplant (UCBT) in a malignant cohort receiving either a high-dose TBI or a medium-intensity conditioning regimen. Methods From 2006-2023, 132 patients were enrolled on a single-arm, phase II study for patients undergoing UCBT after myeloablative preparative regimen with either cyclophosphamide , fludarabine and 13.2Gy total body irradiation (TBI) (Reg A) or cyclophosphamide , fludarabine , thiotepa and 4Gy TBI (Reg B) for the treatment of hematologic malignancies . Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and mycophenolate mofetil. Kaplan-Meier or cumulative incidence estimates were used to summarize point estimates of overall survival (OS), progression-free survival (PFS), relapse, and non-relapse mortality (NRM). Cox regression was used to compare outcomes between treatment regimens (high-intensity vs. medium-intensity regimens) and between patients with vs. without measurable residual disease (MRD). Results Median follow-up among 93 survivors was 3.5 years and median age at time of transplant was 20. Fifty-seven of 132 enrolled were female. The most common indications for transplant were acute myeloid leukemia (n=57) and acute lymphoblastic leukemia (n=48). 51 patients received a single cord-blood unit and 81 received double-cord units. 105 patients received Reg A whilst 27 patients received Reg B. Average total nucleated cell dose was 5.42 × 10^7/kg. Median time to engraftment was 21 days with 3 patients experiencing primary graft failure . Incidence of grade III-IV acute GVHD was 20%. Estimates of OS, PFS, relapse, and NRM in the entire cohort, the acute leukemia cohort (patients with AML , ALL or myelodysplastic syndrome , n=114) and the pediatric leukemia cohort (patients </= 21, n=64) are represented in figures 1-3. Table 1 summarizes comparisons for each examined outcome between Regimens B and A for all patients, and between MRD+ and MRD- patients in the acute leukemia cohort. Discussion The data from this single center prospective trial demonstrate excellent overall outcomes for patients undergoing UCBT. A comparison between the medium-intensity and high-dose TBI regimens yielded numerical increases in the hazard of failure for each outcome, although none were large enough to draw definitive conclusions. In contrast to other stem cell sources, this analysis saw no evidence of increased relapse among patients with MRD relative to those without MRD. These results highlight the utility of UCB as a donor source for HSCT.

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.jtct.2025.01.018