Primary Analysis of the Endrad Trial: Non-Total Body Irradiation (TBI) Conditioning and Allogeneic Hematopoietic Cell Transplantation (HCT) in Next-Generation-Sequencing Minimal Residual Disease (NGS-MRD) Negative B-Acute Lymphoblastic Leukemia (B-ALL) of Children, Adolescents, and Young Adults (CAYA) with High-Risk/Relapsed B-ALL with Planned Comparisons to the Observational Cohort (Pediatric Transplantation and Cellular Therapy Consortium ONC1701)

Document Type

Conference Proceeding

Publication Date

2-2026

Publication Title

Transplantation and Cellular Therapy

Abstract

Introduction: HCT is an established curative treatment for CAYA with high-risk/relapsed B-ALL. Use of TBI, vs non-TBI conditioning, has been associated with better LFS but also with significant late effects. We hypothesized that CAYA with pre-HCT negative NGS-MRD receiving non-TBI conditioning could achieve outcomes comparable to patients receiving TBI.

Objectives/Methods: PTCTC conducted a phase II prospective trial at 45 centers in North America (NCT03509961; 2018-25) to evaluate outcomes of myeloablative non-TBI conditioning for allogeneic HCT in B-ALL patients at lower risk for relapse defined by absence of pre-HCT NGS-MRD (Clonoseq™) of B-cell receptor rearrangements. Prior blinatumomab (BLIN), inotuzumab (INO), or CAR-T therapies were allowed. All graft sources were permitted. GVHD prophylaxis was according to graft source and institutional standards.

Results: 51 patients in CR1 (49%) or CR2 (51%) received HCT on the study treatment arm. Median age at diagnosis and HCT were 11.9 and 13.5 years, respectively. Pre-HCT, 65%, 8%, and 33% of patients received BLIN, INO, or CAR-T, respectively. 86% of patients received the preferred study non-TBI regimen (busulfan, fludarabine, thiotepa). Donors included matched sibs 37%, mismatched related/haplo 35%, matched unrelated 20%, or unrelated cord blood 8%. Donor graft sources were 71% bone marrow and 21% peripheral blood stem cells. At a median follow-up of 2.3 (range: 0.2-6.0) years, the 2-year OS and EFS were 82.1% and 76.3%, respectively. Age at HCT (≤10 vs >10yrs) and prior BLIN were associated with decreased EFS (HR= 1 vs 0.2, p=0.0080) and (HR=3.7 vs 1, p=0.047), respectively. Acute GVHD occurred in 20 patients (39%, with 15 (75%) grade 1-2 and 5 (25%) grade 3-4). Chronic GVHD occurred in 13 patients (25%; 11 (85%) requiring systemic immunosuppressive treatment). When compared to the observational cohort of the study, age (at diagnosis and HCT) was also associated with EFS and OS, and NGS-MRD positivity was significantly associated with poor outcomes for all endpoints. No differences were noted in relapse, RFS, or OS in patients receiving TBI vs. non-TBI regimens (see Figures).

Conclusions: Younger age at diagnosis and HCT and prior BLIN therapy were associated with inferior outcomes. NGS-MRD positivity was significantly associated with poor outcomes for all endpoints. OS in our treatment cohort is comparable to published CIBMTR results in B-ALL where patients predominantly received TBI-based conditioning. Our results show that pre-HCT NGS-MRD can be used to allow the choice of myeloablative non-TBI conditioning for CAYA undergoing allogeneic HCT with outcomes similar to TBI-based approaches. Additional analyses to be reported at the meeting include assessment of clinical factors that impact post-HCT outcomes (e.g. GVHD, cytogenetics, and post-HCT BM and PB NGS-MRD) in both our treatment (n=51) and observational (n=151) cohorts.

Volume

32

Issue

2 Suppl

First Page

s98

Comments

Helen DeVos Children's Hospital

Tandem Meetings of ASTCT and CIBMTR, Feb 4-7, 2026, Salt Lake City, UT

Last Page

s99

DOI

10.1016/j.jtct.2025.12.144

ISSN

2666-6367

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