1.
Clofarabine and busulfan myeloablative conditioning in allogeneic hematopoietic cell transplant for patients with active myeloid malignancies
Connor, M. P., Loren, A. W., Hexner, E. O., Martin, M. E., Gill, S. I., Luger, S. M., Mangan, J. K., Perl, A. E., McCurdy, S. R., Pratz, K. W., et al
Transplantation and cellular therapy. 2022
Abstract
BACKGROUND Patients with refractory or relapsed and refractory myeloid malignancies have a poor prognosis. Allogeneic hematopoietic cell transplant (HCT) with myeloablative conditioning (MAC) in patients with active, chemotherapy-refractory myeloid disease is historically associated with high rates of relapse and non-relapse mortality. A MAC regimen combining clofarabine with busulfan (Clo/Bu4) has been described to exhibit anti-leukemic activity with acceptable toxicity in patients ≤ 70 years old. OBJECTIVES To describe clinical outcomes of a real-world population of patients with active myeloid malignancies undergoing allogeneic HCT with Clo/Bu4 MAC. STUDY DESIGN In a single-center, retrospective descriptive analysis, we identified patients who underwent HCT for myeloid malignancies not in remission using Clo/Bu4 MAC between 2012 and 2020. We report event-free (EFS) and overall survival (OS), cumulative incidence of relapse, non-relapse mortality (NRM), and incidence and severity of acute and chronic graft-versus-host disease (GVHD). RESULTS We identified 69 patients with a median age of 60 years (range 22-70). Most patients had relapsed/refractory or primary refractory acute myeloid leukemia (AML, n = 55), or refractory myelodysplastic syndrome (MDS, n = 12); one patient had chronic myeloid leukemia and one had blastic plasmacytoid dendritic cell neoplasm. Fifty patients (72.5%) had complete remission at day 100 after transplant. Two-year EFS and OS were 30% (95% CI 20-44) and 40% (95% CI 29-54), respectively. Patients with AML had 2-year EFS and OS of 28% (95% CI 18-44) and 38% (95% CI 27-54), respectively; those with MDS had 2-year EFS and OS of 47% (95% CI 25-88) and 56% (95% CI 33-94), respectively. Cumulative incidence of relapse at 2 years was 39% (95% CI 27-51) for all patients: 45% (95% CI 31-58) in AML and 18% (95% CI 2-45) in MDS. NRM at 2 years was 31% (95% CI 20-42): 27% (95% CI 15-39) in AML and 35% (95% CI 10-63) in MDS. The total incidence of aGVHD of any severity was 80%. Incidence of grade 3-4 aGVHD at was 22%. In patients who achieved remission, those who required systemic immunosuppression for aGVHD (58%) had poorer 2-year EFS (29% versus 54%, p = 0.05) and 2-year OS (39% versus 70%, p = 0.04) compared to those who did not. The 2-year cumulative incidence of cGVHD was 44% (95% CI 28-58). CONCLUSIONS Clo/Bu4 MAC followed by allogeneic HCT for patients with active myeloid malignancies is an effective transplant strategy up to age 70, particularly for those with advanced MDS. High incidence of and poor outcomes associated with aGVHD highlight the importance of optimizing preventative strategies.