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Clinical Trial
. 2020 Mar 30;13(1):27.
doi: 10.1186/s13045-020-00860-y.

Haploidentical donor is preferred over matched sibling donor for pre-transplantation MRD positive ALL: a phase 3 genetically randomized study

Ying-Jun Chang  1 , Yu Wang  1 , Lan-Ping Xu  1   2 , Xiao-Hui Zhang  1 , Huan Chen  1 , Yu-Hong Chen  1 , Feng-Rong Wang  1 , Wei-Han  1 , Yu-Qian Sun  1 , Chen-Hua Yan  1   2 , Fei-Fei Tang  1 , Xiao-Dong Mo  1   2 , Yan-Rong Liu  1 , Kai-Yan Liu  1 , Xiao-Jun Huang  3   4   5
Affiliations
Clinical Trial

Haploidentical donor is preferred over matched sibling donor for pre-transplantation MRD positive ALL: a phase 3 genetically randomized study

Ying-Jun Chang et al. J Hematol Oncol. .

Abstract

Background: Previous reports suggest a benefit associated with haploidentical donor transplantation (HIDT) compared to matched sibling donor transplantation (MSDT) in certain contexts, and the choice of optimal candidates warrants further investigation.

Methods: We designed a prospective genetically randomized study to evaluate donor options between acute lymphoblastic leukemia (ALL) patients positive for measurable residual disease (MRD) pre-transplantation who underwent HIDT (n = 169) or MSDT (n = 39).

Results: The cumulative incidence of positive MRD post-transplantation was 26% (95% CI, 19-33%) and 44% (95% CI, 28-60%) for HIDT and MSDT, respectively (P = 0.043). Compared to the HIDT cohort, the MSDT cohort had a higher 3-year cumulative incidence of relapse (CIR; 47%, 95% CI, 31-63% vs. 23%, 95% CI, 17-29%; P = 0.006) and lower 3-year probability of leukemia-free survival (LFS; 43%, 95% CI, 27-59% vs. 65%, 95% CI, 58-72%; P = 0.023) and overall survival (OS; 46%, 95% CI, 30-62% vs. 68%, 95% CI, 61-75%; P = 0.039), without a difference in non-relapse-mortality (10%, 95% CI, 1-19% vs. 11%, 95% CI, 6-16%; P = 0.845). Multivariate analysis showed that HIDT is associated with a low CIR (HR = 0.364; 95% CI, 0.202-0.655; P = 0.001) and better LFS (HR = 0.414; 95% CI, 0.246-0.695; P = 0.001) and OS (HR = 0.380; 95% CI, 0.220-0.656; P = 0.001).

Conclusions: HIDT is better than MSDT in view of favorable anti-leukemia activity for patients with pre-transplantation MRD positive ALL. The current study paves the way to determine that haploidentical donors are the preferred choice regardless of available matched sibling donors in a subgroup population.

Trial registration: ClinicalTrials.gov Identifier: NCT02185261. Registered July 9, 2014. https://clinicaltrials.gov/ct2/show/NCT02185261?term=NCT02185261&draw=2&rank=1.

Keywords: Acute lymphoblastic leukemia; Donor selection; Haploidentical donor transplantation; Matched sibling donor transplantation; Measurable residual disease.

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Conflict of interest statement

The authors declared that they have no competing interests.

Figures

Fig. 1
Fig. 1
CONSORT (the Consolidated Standards of Reporting Trials) diagram. Abbreviations: ALL, acute lymphoblastic leukemia; CR, complete remission; HLA, human leukocyte antigen; MRD, measurable residual disease; MSDT, human leukocyte antigen-matched sibling donor transplantation; Haplo-SCT, haploidentical stem cell transplantation
Fig. 2
Fig. 2
Outcome of allogeneic stem cell transplantations in two cohorts after a median follow-up of 820 days. a Cumulative incidence of positive measurable/minimal residual disease after transplantation (overall P value for uni- and multivariate analysis was 0.024 and 0.018). b Cumulative incidence of leukemia relapse (overall P value for uni- and multivariate analysis was 0.008 and 0.001). c Non-relapse mortality (overall P value for uni- and multivariate analysis was 0.869 and 0.478). d Leukemia-free survival (overall P value for uni- and multivariate analysis was 0.025 and 0.001). e Overall survival (overall P value for uni- and multivariate analysis was 0.042 and 0.001). Abbreviations: Haplo-SCT, haploidentical stem cell transplantation; MSDT, human leukocyte antigen-matched sibling donor transplantation; MRD, measurable residual disease
See this image and copyright information in PMC

References

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