A novel protocol of dual passing cord blood pre-/post-transplant reduced relapse in TCRαβ cell depleted HCT

Abstract Background How to overcome post-transplant relapse (PTR) is the main challenge in current. PTR is 20% or higher in haplo-HCT. An advantage of overcoming PTR was proved in TCRαβ cell depleted HCT (TDH). There are reports showed a significant reduction in PTR with ATG-free conditioning or immunosuppressants-free after TDH. Given that unrelated cord blood (UCB) has a good anti- leukemia effect, we hypothesize that the addition of dual passing UCB before and after transplant to the TDH can further reduce PTR. Patients and Methods From Sep. 2020 to Jun. 2025, 101 patients underwent TDH, with median age 8 (1-75) year old and median follow-up time (MFU) 24 (2-58) months, including 74 lymphoid and 27 myeloid diseases. The disease status at TDH were 40 at CR1, 42 at CR2, 19 at > CR3 or progress ( the latter two (≥ CR2) together was 61). Patients received different conditioning regimens composed of Busulfan or Melphalan, Cyclophosphamide, Fludalabine and Thiotepa, and the doses of them were adjusted according to the disease status and kinds. No GVHD prophylaxis was used. All patients received Decitabine plus DLI, monthly for 6 time. The infused doses of CD34+, MNC and NK cells were 27.5 (20.5-38.4)×106/kg, 11.4 (7.9-14.8)×108/kg, and 105.7 (80.3-160.9)×106/kg, respectively. Seventy-five patients with MRD+ or higher received Car-T prior to transplant if available. 42 patients received UCB 7 to 10 days before TDH (matched to patients as possible) and 3-5 days after transplant (mismatched to patients and Kir favorable). The CR1 vs. ≥ CR2 groups, lymphoid vs. myeloid leukemia, Car-T vs. non-Car-T, UCB vs. non-UCB in total, and UCB (n=26) vs. non-UCB (n=35) and Car-T (n=52) vs. non-Car-T (n=9) in ≥ CR2 group were compared. Results Five patients rejected their grafts and 2 died of infection before engraftment. The rate of engraftment was 93.1% (94/101). ANC time to 0.5x109/L and platelet time to 20x109/L were 14 (12-15) and 9 (8-11) days, respectively. The OS, EFS, relapse, TRM and relapse-free survival (RFS), in total, were 87.6%, 78.7%, 9.6%, 7.4% and 82.7%, respectively. Corresponding data, in CR1 cohort, were 94.9%, 87.4%, 0%, 5.1% and 94.9%, respectively. The RFS of CR1 group with MFU of 26 months was better than ≥ CR2 group with MFU of 23 months (94.9% vs. 74.7% p= 0.02). The cumulative relapse rate in the ≥CR2 group was higher than CR1 group (16% vs.0%, p = 0.017). The positive events of the current study too few to find significant difference in comparison of Car-T vs. non-Car-T, UCB vs. non-UCB, and lymphoid vs. myeloid leukemia in total. While, UCB subgroup (n: 26, MFU: 15.5 months) compared to non-UCB subgroup (n: 35, MFU:29 months) in ≥ CR2 group showed a tendency reduced recurrence (85.6% vs. 68.2%, p=0.135), but not in Car-T vs. non-Car-T (75.6 % vs.71.1%, p=0.939). Acute GVHD occurred in 31.9% (30/94) of patients, and 93.33% (28/30) were at gradesⅠ-Ⅱ, and 6.67% (2/30) were at grades Ⅲ-Ⅳ. Chronic GVHD occurred in 11.7% (11/94) of patients. Of them, 54.6% (6/11) was grade I, and 45.5% (5/11) were I grade II and III Summary Our TDH protocol showed promising results with 94.9% RFS in CR1 group and PTR and TRM below 10% in the cohort in which ≥ CR2 patients were more than 60%. None of relapse occurred in the CR1 group. In the ≥ CR2 group the UCB subgroup showed a PTR reduced tendency.