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Clinical Trial
. 2021 Nov 4:12:733326.
doi: 10.3389/fimmu.2021.733326. eCollection 2021.

Sequential Transplantation of Haploidentical Stem Cell and Unrelated Cord Blood With Using ATG/PTCY Increases Survival of Relapsed/Refractory Hematologic Malignancies

Hua Li  1 , Xiaofan Li  1   2 , Yiling Chen  1 , Duihong Li  1 , Xianling Chen  1 , Zhijuan Zhu  1 , Yiting Wang  1 , Jiafu Huang  1 , Ping Chen  1 , Yuanzhong Chen  1   2 , Nainong Li  1   2
Affiliations
Clinical Trial

Sequential Transplantation of Haploidentical Stem Cell and Unrelated Cord Blood With Using ATG/PTCY Increases Survival of Relapsed/Refractory Hematologic Malignancies

Hua Li et al. Front Immunol. .

Abstract

Allogeneic haploidentical HSCT (haplo-HSCT) and unrelated umbilical cord blood transplantation(UCBT)are used in patients lacking HLA-identical sibling or unrelated donors. With myeloablative condition and GVHD prophylaxis of using low-dose ATG and post-transplantation cyclophosphamide (PTCY), we conducted a prospective clinical trial. Of eligible 122 patients from February 2015 to December 2019 in the study, 113 patients were involved. Forty-eight patients were in the group of sequential haplo-cord transplantation (haplo-cord HSCT), and 65 patients were in the group of single UCBT. The primary endpoint of 2-year disease-free survival (DFS) was no statistical difference between groups (64.1 vs. 56.5%), p>0.05. The analysis of subgroup patients with relapsed/refractory showed haplo-cord HSCT was associated with better OS (HR 0.348, 95% CI, 0.175-0.691; p=0.0025), DFS (HR 0.402, 95% CI, 0.208-0.779; p=0.0069), and GRFS (HR 0.235, 95% CI, 0.120-0.457, p<0.0001) compared to the single cord group. The 2-year's probability in OS, DFS, and GRFS was 64.9 vs. 31.6%, 64.5 vs. 31.6%, and 60.8 vs. 15.0% in the haplo-cord group and single cord group, respectively. III-IV acute GVHD 8.3 vs. 6.2%, chronic GVHD 25.8 vs. 13.7%, and extensive chronic GVHD 5.3 vs. 1.8% were shown in corresponding group, p>0.05. The patients engrafted persistently with UCB showed better survival outcomes. Our sequential Haplo-cord HSCT with ATG/PTCY improved the survival of patients and might be an alternative transplantation approach for patients with relapsed/refractory hematologic malignancies.

Keywords: low-dose ATG; post-transplant cyclophosphamide; relapsed/refractory hematologic malignancies; sequential transplantation; umbilical cord blood transplantation.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Flowchart of the cohort.
Figure 2
Figure 2
Myeloablative Conditioning Regimens for haplo-cord HSCT (A) and single cord HSCT (B). Flu, Fludarabine; Ara-C, cytarabine; CTX, Cyclophosphamide; Bu, busulfan; ATG, anti-thymocyte globulin; MMF, Mycophenolate mofetil; CsA Cyclosporin; PBSC, peripheral blood hematopoietic stem cells; UCB, umbilical cord blood stem cells.
Figure 3
Figure 3
Cumulative incidences of (A) neutrophil recovery and (B) platelet recovery in haplo-cord HSCT and single cord HSCT group after IPTW.
Figure 4
Figure 4
The relapse/refractory patients’ outcomes of haplo-cord HSCT and single UCB-HSCT group after IPTW. (A) OS, (B) DFS, (C) GRFS, (D) NRM.
Figure 5
Figure 5
The survival outcomes of haploidentical engraftment and umbilical cord blood engraftment in haplo-cord HSCT group. (A) OS, (B) DFS, (C) GRFS, (D) RI, (E) RM, (F) NRM.
See this image and copyright information in PMC

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