Haploidentical transplantation has a superior graft-versus-leukemia effect than HLA-matched sibling transplantation for Ph- high-risk B-cell acute lymphoblastic leukemia

Menglin Fan, Yu Wang, Ren Lin, Tong Lin, Fen Huang, Zhiping Fan, Yajing Xu, Ting Yang, Na Xu, Pengcheng Shi, Danian Nie, Dongjun Lin, Zujun Jiang, Shunqing Wang, Jing Sun, Xiaojun Huang, Qifa Liu, Li Xuan, Menglin Fan, Yu Wang, Ren Lin, Tong Lin, Fen Huang, Zhiping Fan, Yajing Xu, Ting Yang, Na Xu, Pengcheng Shi, Danian Nie, Dongjun Lin, Zujun Jiang, Shunqing Wang, Jing Sun, Xiaojun Huang, Qifa Liu, Li Xuan

Abstract

Background: Compared with human leukocyte antigen (HLA)-matched sibling donor (MSD) transplantation, it remains unclear whether haploidentical donor (HID) transplantation has a superior graft-versus-leukemia (GVL) effect for Philadelphia-negative (Ph-) high-risk B-cell acute lymphoblastic leukemia (B-ALL). This study aimed to compare the GVL effect between HID and MSD transplantation for Ph- high-risk B-ALL.

Methods: This study population came from two prospective multicenter trials (NCT01883180, NCT02673008). Immunosuppressant withdrawal and prophylactic or pre-emptive donor lymphocyte infusion (DLI) were administered in patients without active graft-versus-host disease (GVHD) to prevent relapse. All patients with measurable residual disease (MRD) positivity posttransplantation (post-MRD+) or non-remission (NR) pre-transplantation received prophylactic/pre-emptive interventions. The primary endpoint was the incidence of post-MRD+.

Results: A total of 335 patients with Ph- high-risk B-ALL were enrolled, including 145 and 190, respectively, in the HID and MSD groups. The 3-year cumulative incidence of post-MRD+ was 27.2% (95% confidence interval [CI]: 20.2%-34.7%) and 42.6% (35.5%-49.6%) in the HID and MSD groups (P = 0.003), respectively. A total of 156 patients received DLI, including 60 (41.4%) and 96 (50.5%), respectively, in the HID and MSD groups (P = 0.096). The 3-year cumulative incidence of relapse was 18.6% (95% CI: 12.7%-25.4%) and 25.9% (19.9%-32.3%; P = 0.116) in the two groups, respectively. The 3-year overall survival (OS) was 67.4% (95% CI: 59.1%-74.4%) and 61.6% (54.2%-68.1%; P = 0.382), leukemia-free survival (LFS) was 63.4% (95% CI: 55.0%-70.7%) and 58.2% (50.8%-64.9%; P = 0.429), and GVHD-free/relapse-free survival (GRFS) was 51.7% (95% CI: 43.3%-59.5%) and 37.8% (30.9%-44.6%; P = 0.041), respectively, in the HID and MSD groups.

Conclusion: HID transplantation has a lower incidence of post-MRD+ than MSD transplantation, suggesting that HID transplantation might have a superior GVL effect than MSD transplantation for Ph- high-risk B-ALL patients.

Trial registration: ClinicalTrials.gov: NCT01883180, NCT02673008.

Conflict of interest statement

None.

Copyright © 2022 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.

Figures

Figure 1
Figure 1
Cumulative incidence of post-MRD+ (A) and relapse (B) for all patients. ∗P < 0.05. CI: Confidence interval; HID: Haploidentical donor; HR: Hazard ratio; MRD: Measurable residual disease; MSD: HLA-matched sibling donor; post-MRD+: Measurable residual disease positivity post-transplantation.
Figure 2
Figure 2
Flow diagram. CsA: Cyclosporin A; DLI: Donor lymphocyte Infusion; HID: Haploidentical donor; MSD: HLA-matched sibling donor.
Figure 3
Figure 3
Cumulative incidence of overall survival (A), leukemia-free survival (B), and graft-versus-host disease-free/relapse-free survival (C) for all patients. P < 0.05. CI: Confidence interval; GVHD: Graft-versus-host disease; HID: Haploidentical donor; HR: Hazard ratio; MSD: HLA-matched sibling donor.

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