Clofarabine and Total Body Irradiation (TBI) as Conditioning Regimen for Allogeneic Stem Cell Transplantation in High-Risk Acute Leukemia Patients.

Abstract Background: Clofarabine (Clo) is an immunosuppressive purine analog that may have better anti-leukemic activity than fludarabine (Flu) in the conditioning regimen for allogeneic stem cell transplant (allo-SCT) for acute leukemia patients. The addition of total body irradiation (TBI) to conditioning regimens has been widely investigated. However, the use of single agent Clo in combination with intermediate doses of TBI ranging from 4-8 Gy has not been studied yet. Objective: This study aims to identify the outcome of patients with high-risk hematological malignancies who underwent allo-SCT from different donor types and received Clo and TBI (4-8 Gy) as a conditioning regimen. Methods: This is a double center, observational, retrospective study of patients with high-risk hematological malignancies diagnosed from 2012 to 2021, treated at the American University of Beirut Medical Center in Beirut (AUBMC), Lebanon, and Saint-Antoine Hospital (SA) in Paris, France. Data regarding patient baseline characteristics, disease-related factors, and transplant outcomes including graft-versus-host disease (GVHD), Non-relapse mortality (NRM), progression-free survival (PFS), and overall survival (OS), were collected. Results: We identified 24 high-risk patients with a median age at transplant of 37 years (range 22-78). Of these, 15 patients (63%) were males, 8 patients (33%) had acute myeloid leukemia (AML), 3 patients (13%) had myelodysplastic syndrome (MDS), and 12 patients (50%) had acute lymphoblastic leukemia (ALL), and 1 patient had B-lymphoblastic lymphoma (B-ALL) (4%). At the time of the transplant, only 15 patients (63%) were in complete remission (CR). Nine patients (38%) received transplants from a matched related donor(MRD), 9 patients (38%) from a haploidentical related donor(haplo), 4 patients (17%) from a matched unrelated donor(MUD), and 2 patients (8%) from an unrelated cord blood donor (UCB). All patients received Clo. For TBI, 21 patients (88%) received a total dose of 4 Gy, and 3 (12%) received 8 Gy. Sixteen patients (67%) received anti-thymocyte globulin(ATG). After a median follow-up of 40 months, the cumulative incidences of grade II-III acute GVHD, grade IV acute GVHD, and chronic GVHD were 50%, 4%, and 8%, respectively. NRM at 100 days, and 1 year after transplant was 4% and 25%, respectively. 17% of the patients had a relapse or progression of the disease by the end of the study. The 2-year PFS and OS were 50% and 56%, respectively. The median PFS and OS were not reached. Conclusions: Clo/TBI (4-8 Gy) as a conditioning regimen for allo-SCT in high-risk patients confers disease control with an acceptable toxicity profile.