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

• Published in: Journal of hematology and oncology Vol. 13; no. 1; pp. 27 - 13
• Main Authors: Chang, Ying-Jun, Wang, Yu, Xu, Lan-Ping, Zhang, Xiao-Hui, Chen, Huan, Chen, Yu-Hong, Wang, Feng-Rong, Wei-Han, Sun, Yu-Qian, Yan, Chen-Hua, Tang, Fei-Fei, Mo, Xiao-Dong, Liu, Yan-Rong, Liu, Kai-Yan, Huang, Xiao-Jun
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 30.03.2020; BioMed Central; BMC
• Subjects: Acute lymphoblastic leukemia; Acute lymphocytic leukemia; Adolescent; Adult; Antitumor activity; Bone marrow; Cancer research; Chemotherapy; Child; Child, Preschool; Comparative analysis; Cytomegalovirus; Diseases; Donor Selection; Donors; Female; Flow cytometry; Haploidentical donor transplantation; Health aspects; Hematology; Humans; Leukemia; Lymphatic leukemia; Lymphocytic leukemia; Male; Matched sibling donor transplantation; Measurable residual disease; Middle Aged; Mortality; Multivariate analysis; Neoplasm, Residual - genetics; Neoplasm, Residual - therapy; Oncology; Patients; Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics; Precursor Cell Lymphoblastic Leukemia-Lymphoma - therapy; Prospective Studies; Siblings; Stem Cell Transplantation - methods; Studies; Surgery; Survival; Tissue Donors; Transplantation; Transplantation, Haploidentical - methods; Transplants & implants; Young Adult; Matched sibling donor transplantation; Haploidentical donor transplantation; Acute lymphoblastic leukemia; Measurable residual disease; Donor selection
• ISSN: 1756-8722; 1756-8722
• DOI: 10.1186/s13045-020-00860-y

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