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Comparison of Myeloablative Conditioning with a Total Body Irradiation-Based Regimen Versus a Chemotherapy-Based Regimen in Adult Patients Undergoing Umbilical Cord Blood Stem Cell Transplant for Ph-Negative Acute Lymphoblastic Leukemia

Year: 2025

Type: article

Abstract: Introduction/Objectives Myeloablative conditioning with high-dose total body irradiation (TBI) before allogeneic hematopoietic stem cell transplantation (HSCT) in acute lymphoblastic leukemia (ALL) is effective, though toxicities may affect long-term survival. Chemotherapy-based regimens have been developed to reduce toxicity, but in pediatric ALL patients undergoing HSCT, TBI-based conditioning has superior survival outcomes compared to chemotherapy-based regimens. The benefit of high-dose TBI in adult ALL, especially in the context of umbilical cord blood transplants, remains less understood. This study compares outcomes in adult patients with ALL who underwent cord blood transplant with either a TBI-based or a chemotherapy-based myeloablative conditioning (MAC) regimen. Methods Adult patients with Philadelphia chromosome (Ph)-negative ALL who underwent cord-blood HSCT with MAC between May 2016 and November 2023 at the University of Colorado Hospital were included. Patients in the TBI-based conditioning group received 12Gy TBI with fludarabine and cyclophosphamide (TBI-MAC), while the chemotherapy-based group received a regimen including thiotepa, fludarabine, cyclophosphamide, and 4Gy TBI (chemo-MAC). Transplants were performed with either dual cord blood units or a combination of cord blood and CD34-selected PBSCs from a haploidentical donor. Results A total of 36 patients were included (17 in the TBI-MAC group and 19 in the chemo-MAC group). The TBI-MAC group was younger (median age 27 vs. 39 years, p=0.019), had fewer patients with B-ALL (41% vs. 74%, p=0.027), and were more frequently transplanted between 2020-2023 compared to the chemo-MAC group (88% vs. 42%, p=0.033). There were no differences in MRD status (MRD-negative 84% vs. 82%, p=1.0), remission stage (58% vs 47% in CR1, p=0.54), or comorbidity scores (ECOG 0-1 94% vs. 100%, p=0.96) between the groups. Cumulative incidence of relapse was 0% in the TBI-MAC group vs. 25% in the chemo-MAC group (p=0.11), while non-relapse mortality was 6% vs. 21% (p=0.4). 100-day cumulative incidence of any acute graft-versus-host-disease (aGVHD) (53% vs. 63%, p=0.6) and grade ≥3 aGVHD (6% vs. 11%, p=1.0) did not differ, nor did cumulative incidence of chronic GVHD (18% vs. 11%, p=0.5). With median follow-up of 11.3 months in the TBI-MAC group and 32.0 months in the chemo-MAC group, one-year relapse free survival (RFS) was 94% vs 66% (p=0.047). Estimated one-year overall survival (OS) was 94% with TBI-MAC vs 78% with chemo-MAC (p=0.058). Conclusion High-dose TBI-based conditioning in Ph-negative ALL patients undergoing cord blood transplant was associated with improved RFS compared to chemotherapy-based regimens, with no significant differences in treatment-related mortality or GVHD. These findings suggest that TBI-based conditioning remains the most effective option for myeloablation in this setting.

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.jtct.2025.01.291