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

• Published in: Blood 2024-11, Vol.144 (Supplement 1), p.7280-7280
• Main Authors: Gilbert, Jason S., Kent, Andrew, Gutman, Jonathan, Amaya, Maria L, McMahon, Christine M., Pollyea, Daniel A, Schwartz, Marc
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2024-200993

Background: Myeloablative conditioning with high dose total body irradiation (TBI) before allogeneic hematopoietic stem cell transplantation (HSCT) in patients with acute lymphoblastic leukemia (ALL) is effective, but short-term toxicities may negatively impact long-term survival. As an attempt to reduce toxicity, myeloablative chemotherapy-based regimens have been developed as alternatives to TBI-based regimens. For pediatric ALL patients undergoing HSCT from HLA-matched donors, survival outcomes are superior with TBI-based conditioning compared to chemotherapy-based conditioning due to reduced relapse. Less is known about the relative benefit of high-dose TBI in adult ALL patients, particularly in the setting of HLA-mismatched umbilical cord blood transplant. We sought to compare outcomes of adult patients with ALL who underwent cord blood transplant with a high dose TBI-based regimen versus a myeloablative chemotherapy-based regimen. Methods: Adult patients with Philadelphia chromosome (Ph) negative ALL who underwent cord-blood HSCT with myeloablative conditioning (MAC) between May 2016 and November 2023 at University of Colorado Hospital were included in this analysis. No patients with Ph-positive ALL underwent HSCT with high-dose TBI during this period. Patients in the high dose TBI-based conditioning regimen group received 12Gy TBI with 75 mg/m2 fludarabine and 120 mg/kg cyclophosphamide (TBI-MAC). Patients in the chemotherapy-based group received a regimen consisting of 10 mg/kg thiotepa, 150 mg/m2 fludarabine, 50 mg/kg cyclophosphamide, and 4Gy TBI (chemo-MAC). Patients were transplanted with two cord blood units (dual cord) or a single cord blood unit combined with CD34-selected PBSCs from a haploidentical donor (haplo-cord). Results: A total of 36 patients were included in this study, with 17 patients conditioned with TBI-MAC and 19 patients with chemo-MAC. The TBI-MAC group was younger (median age 27 years vs. 39 years, p=0.019), included fewer patients with B-ALL (41% vs. 74%, p=0.027) compared to T-ALL, and more frequently were transplanted between 2020-2023 compared to the chemo-MAC group (88% vs. 42%, p=0.033). There were no differences in proportion of patients transplanted in CR1 (58% vs 47%, p=0.54) versus CR2/CR3, MRD status by flow pre-SCT (MRD-negative 84% vs. 82%, p=1.0), proportion of patients who underwent dual cord (35% vs. 42%, p=0.8) versus haplo-cord SCT, or comorbidity scores (ECOG 0-1 94% vs. 100%, p=0.96). Cumulative incidenc