Total marrow irradiation based conditioning for allogeneic hematopoietic stem cell transplantation in elderly or frail patients with hematological malignancies: A single center analysis

Abstract Background：Allogeneic hematopoietic stem-cell transplantation (allo-HSCT) remains the only potentially curative therapy for many hematological disorders, yet standard high-dose chemoradiation conditioning is associated with substantial toxicity-related mortality, especially in older adults or those with poor performance status. Total marrow irradiation (TMI) is a high precision radiation technique that can deliver ablative doses to targeted marrow sites while markedly reducing exposure of vital organs compared with conventional total-body irradiation (TBI). Here we report the results of a retrospective analysis of allo- HSCT following TMI based conditioning in elderly and frail patients with the intent of limiting toxicity. Methods: Patients aged ≥ 60 years, or with ECOG performance status ≥ 3, or with HCT-CI ≥ 3, who underwent allo-HSCT following TMI-based conditioning between May 2023 and May 2025 were enrolled in this study. All patients received 12Gy TMI (one patient 10 Gy) delivered in 3 consecutive days in two daily fractions using helical tomotherapy. Additional radiation fields were added as clinically indicated: total lymphoid irradiation ± splenic boost (n = 5), or craniospinal irradiation 16–24 Gy for central-nervous-system (CNS) leukemia (n = 7). Conditioning was supplemented with fludarabine 30 mg/m² × 5 days and thiotepa 5 mg/kg was also added in two cases. Post-transplant cyclophosphamide(PtCy) based graft-versus-host disease (GVHD) prophylaxis was used in 18 patients. Donor sources were HLA-matched sibling (n = 4) or haploidentical (n = 16). Results: Twenty patients were enrolled. Briefly, eight patients were over sixty years old. Ten patients were affected by acute myeloid leukemia (AML) and seven of them were non-remission at transplantation. Two patients were diagnosed as chronic active Epstein-Barr virus disease (CAEBV) with one of them was in active disease. CNS leukemia was confirmed in seven patients. Median follow-up was 255 days (range 52–662). All patients achieved engraftment with median neutrophil and platelet recovery of 14 days (11–18) and 16 days (10–28), respectively. The 100-day cumulative incidence of grade II–IV acute GVHD was 25.0 ± 5.0%, and the 1-year incidence of moderate/severe chronic GVHD was 31.5 ± 5.2%. At last follow-up, three patients had died from non-relapse reasons and one patient with active disease at transplant had relapsed and died. One-year non-relapse mortality was 13.6 ± 9.4%, and the 1-year cumulative incidence of relapse was 5.6 ± 5.4%. One-year overall survival was 79.2 ± 11.0%, and disease-free survival was 81.6 ± 10.0%. Conclusions: In this high-risk, elderly or frail cohort, TMI-based conditioning achieved rapid engraftment, low relapse rates, and acceptable non-relapse mortality, supporting its potential as a less toxic alternative to conventional myeloablative conditioning regimens. Prospective randomized trials are warranted to confirm the safety and efficacy of TMI-based conditioning in this vulnerable population.