A Baltimore-modified non-TBI conditioning for allogeneic stem cell transplantation in elderly or unfit patients with haploidentical or mismatched donors

Abstract

Abstract Background: The Baltimore conditioning regimen is nowadays one of the most used reduced-intensity conditioning (RIC) regimens, although access to total body irradiation (TBI) may be challenging in some centers. Objective: The aim of this study was to evaluate the outcomes following a non-TBI modified Baltimore RIC regimen consisting of fludarabine, cyclophosphamide and busulfan (FE2B2) in allogeneic stem cell transplantation (Allo-SCT) with haploidentical or mismatched unrelated donor (MMUD) transplantation, with post-transplant high-dose cyclophosphamide-based graft-versus-host disease (GVHD) prophylaxis. Study Design: We conducted a non-interventional, monocentric, retrospective cohort study at a tertiary care center (Grenoble-Alpes University Hospital). We included adult patients (> 18 years) who received an HLA haploidentical or a MMUD allogeneic peripheral blood stem cell graft with a non-TBI modified Baltimore conditioning regimen. The primary endpoint of the study was overall survival (OS) at 2- and 5-years post transplantation. Secondary endpoints were donor engraftment, progression-free survival (PFS), non-relapse mortality (NRM), GVHD-free, relapse-free survival (GRFS), and the incidence of acute and chronic GVHD at 2- and 5-years post-transplantation. Results: A total of 65 adult patients who received the FE2B2 regimen between March 1st, 2016, and April 20th, 2022, were included. The median age of the recipients was 66 years. One-third of the patients had an HCT-CI score ≥ 3. Twenty-eight patients (43%) received a transplant from an haploidentical donor, and 37 patients (57%) received a transplant from a MMUD. The median follow-up was 61 months (range 9-107). Neutrophil engraftment was observed in all the patients, and platelet engraftment in 97% of patients. The cumulative incidences of grade II-IV and grade III-IV aGVHD were 45% (95% CI, 34–59) and 14% (95% CI, 8–25) respectively. Two and five-year cumulative incidences of chronic GVHD and moderate/severe chronic GVHD were 20% (95% CI, 13–32) and 12% (95% CI, 7–23). The 2 and 5-year NRM was 22% (95% CI, 14–34) and respectively 25% (95% CI 17–39). Four patients died within the first 20 days due to hemorrhagic complications (n = 3) or cardiogenic shock secondary to pericarditis (n = 1). The 2 and 5-year PFS, OS and GRFS were 43% (95% CI, 31–55) and 32% (95% CI, 21–44), 48% (95% CI, 35–60) and 37% (95% CI, 25–49), 29% (95% CI, 18–40) and 19% (95% CI, 9–30) respectively. Conclusion: In our cohort of elderly and/or frail patients with high-risk disease, this regimen presents acceptable toxicity, with long-term outcomes in line with published data concerning the classical Baltimore conditioning. Thus, it may be proposed as an alternative in centers with limited access to TBI.

The authors' abstract, as published at the source. Annals of Hematology, 2026 · DOI ↗