A Novel Post-Transplant Regimen for Selectively Promoting Unrelated Cord Blood Engraftment in Haploidentical-Cord Transplantation in Childhood Leukemia: A Single-Arm, Dual-Center Trial
Authors: Ruan Yongsheng , Wang Xiaodong , He Yuelin , Liu Xuan , Liu Qiujun , Xiao Yuhua , Li Chunfu , Liu Sixi , Feng Xiaoqin 
Published: December 2023

Background
Our previous studies indicated that complementary transplantation that was combined with a haploidentical peripheral blood stem cell (PBSC) transplant (haplo-SCT) and unrelated cord blood (UCB) transplant using a post-transplant cyclophosphamide (PTCy) regimen was applicable in children with acute leukemia. A better leukemia-free survival (LFS) was found in the UCB engraftment group, however, the engraftment of PBSC or UCB was unpredictable in the setting of complementary transplantation. Here, we conducted a prospective single-arm dual-center trial to investigate the effect of post-transplant cyclophosphamide plus fludarabine regimen for selectively promoting UCB engraftment in haploidentical-cord transplant.
Methods
This updated conditioning regimen was performed in two hospitals in China, including a total of eligible 78 pediatric patients who were enrolled from September 2019 to October 2022. The median follow-up was 24 months. This study is in progress. Meanwhile, 55 historically consecutive patients from December 2012 to June 2019 were included for comparison. The updated conditioning regimen (PT-Cy/Flu group) consisted of fludarabine (40mg/m 2, d-5 to d-3 and d+3, d+4), busulfan (100mg/m 2, d-6 to d-3), haplo-PBSC (d0), PTCy (50mg/kg, d+3, d+4) and UCB (d+6). The fludarabine was applied at d-6 to d-2 in the original conditioning regimen (PT-Cy group). In addition to PTCy, tacrolimus or cyclosporine and mycophenolate mofetil were administered as prophylaxis of GVHD. The primary aim was the UCB engraftment rate. In addition, the 2-year mid-term inspection included overall survival (OS), LFS, non-relapse mortality (NRM), graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS), and cumulative incidence of acute and chronic GVHD.
Results
The characteristic of patients were shown in Table 1. In brief, 47 (60.3%) acute myeloid leukemia and 27 (34.6%) acute lymphoblastic leukemia pediatric patients were included. 64 (82.1%) patients achieved first complete remission (CR1) before SCT. The median of PBSC mononuclear cells was 20.0×10 8/kg and CD34 + cells was 12.1×10 6/kg, while the median of CB total nuclear cells was 5.0×10 7/kg and CD34 + cells was 1.8×10 5/kg. Eventually, 73 (93.6%) patients in the PT-Cy/Flu group achieved full UCB engraftment by short tandem repeat (STR) detection, while the UCB engraftment rate was 24 (43.6%) in the PT-Cy group (p&lt;0.001). The OS of the PT-Cy/Flu group was 88.6% ± 4.0% (95%CI 81.2% - 96.7%), which was significantly higher than the PT-Cy group [60.0% ± 6.6% (95%CI 48.4% - 74.5%), p&lt;0.001] (Figure 1A). Of note, the LFS was markedly higher in the PT-Cy/Flu group compared to PT-Cy group [83.2% ± 4.3% (95%CI 75.2% - 92.0%) vs. 54.2% ± 6.8% (95%CI 42.4% - 69.2%), p&lt;0.001] (Figure 1B). However, there was no statistical difference in NRM between the PT-Cy/Flu and PT-Cy groups (7.7% ± 0.1% vs 12.7% ± 0.2%, p=0.326). Moreover, similar cumulative incidence of III-IV acute GVHD and severe chronic GVHD were found between groups (Figure 1C, D). Finally, the GRFS of the PT-Cy/Flu was obviously better than the PT-Cy group [70.1% ± 5.9% (95%CI 59.5% - 82.5%) vs 39.4% ± 7.6% (95%CI 27.0% - 57.5%), p=0.025] (Figure 1E).
Conclusion
These results suggested that the novel post-transplant cyclophosphamide plus fludarabine regimen can be considered as a strategy for selectively facilitating UCB engraftment and improving LFS in haploidentical-cord transplant in children with acute leukemia.