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

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.