Total marrow irradiation-based, intensified reduced-intensity conditioning regimen for hematopoietic cell transplantation in patients aged 60 years or older: A prospective study Free

Introduction

Although non-myeloablative conditioning regimens are an established option for elderly patients undergoing hematopoietic cell transplantation (HCT), the best reduced-intensity conditioning (RIC) regimen has yet to be determined. Here, we present a single-center analysis of a prospective study using a total marrow irradiation-based RIC regimen in HCT patients aged 60 years or older.Methods

Patients were included in the current study between 2017 and 2024. Patients received HCT with a conditioning regimen consisting of intravenous busulfan (total area under the curve, AUC, of 9,600 µM*min), fludarabine (total dose of 150 mg/m²), and total marrow irradiation (6 Gy, administered in two days with two daily doses of 1.5 Gy). Four patients received 4.5 Gy as part of the Phase I trial. One patient received busulfan with a total AUC of 9,000 µM*min. Central nervous system or spleen radiotherapy boost was allowed, according to the attending physician. All patients who underwent haploidentical HCT received PTCy (80-100 mg/kg total dose), tacrolimus, and mycophenolate. Other patients received tacrolimus and short-couse methotrexate prophylaxis. Patients with a matched unrelated donor (MUD) or mismatched related donor also received ATG 3 mg/kg. This study was registered at ClinicalTrials.gov under NCT02129582.Results

We included 28 patients, with a median follow-up of 34 months. Median age was 67 years (SD: 5.6), and there were 7 patients with a female donor to a male patient. Main diagnoses were acute myeloid leukemia (16), followed by myelodysplasia (6). HCT-CI was 3+ in 33% of the patients. Interestingly, 14 patients (50%) had refractory or active disease. 86% received a peripheral blood graft, while 14% received a bone marrow transplant. Neutrophil engraftment was 93% (median: 17 days), but one patient died at day 18 without achieving neutrophil engraftment (the other one died at day 42 without signs of neutrophil engraftment). Rate of platelet engraftment was 86%, with a median of 22 days (4 patients died at days 18, 42, 83, and 134 without platelet engraftment).

The 24-month progression-free survival rate was 45% (95% CI, 29-69%). The progression-free survival was 53% for patients in remission and 33% for patients with active disease (p=0.40). The 24-month overall survival rate was 45% (95% CI, 30-69%). The corresponding rates for relapse/progression were 30% (95% CI, 17-54%) and, for non-relapse mortality, 23% (95% CI, 11-45%). Rate of grades II-IV acute GVHD was 47% and III-IV acute GVHD, 8%. 24-month chronic GVHD rate was 19%.Discussion

In this unicenter analysis of a prospective multicenter study, we have shown promising results with total marrow irradiation, RIC-intensified regimen for elderly patients, aged 60 years or older undergoing HCT. Despite the very poor prognosis of patients, with than half having refractory or active disease before the transplant, overall survival was relatively high, with few relapses/progression. Moreover, neutrophil engraftment was very high (93%), with low rates of non-relapse mortality in this fragile population. These results show a good balance between the effectiveness of the conditioning regimen and toxicity. Future studies should confirm these promising results in TMI-based RIC conditioning using a larger patient cohort.Acknowledgements

The authors declare no conflict of interest.