CT-028 Clofarabine and Total Body Irradiation as a Conditioning Regimen for Allogeneic Stem Cell Transplantation in High-Risk Acute Leukemia

Abstract

Clofarabine is an immunosuppressive purine analog that may have better anti-leukemic activity than fludarabine as a conditioning regimen for stem cell transplantation in acute leukemia. The addition of total body irradiation (TBI) to conditioning regimens has been widely investigated. However, the use of single-agent clofarabine in combination with higher doses of TBI ranging from 4 to 8 Gy has not been studied. The aim of this study is to identify the outcome of patients with hematological malignancies who underwent allogeneic stem cell transplantation from full-matched or haploidentical donors and received clofarabine and TBI as a conditioning regimen. This is a double center, observational, retrospective study of patients diagnosed with high-risk acute leukemia (2015-2020) and treated at the American University of Beirut Medical Center in Lebanon and Saint-Antoine Hospital in Paris, France. Data regarding patient baseline characteristics, disease-related factors, and transplant outcomes, including progression-free survival (PFS), overall survival (OS), graft-versus-host disease (GvHD), and transplant-related mortality (TRM) were collected. We identified 23 patients with a median age of 43 years (range 21-78). Of them, 14 (61%) were male, 11 (48%) had acute myeloid leukemia, and 11 (48%) had acute lymphoblastic leukemia. At time of transplant, 14 patients (61%) were in complete remission and 8 patients (35%) had refractory disease. Nine patients (39%) received transplants from a matched related donor, 8 (35%) from a haploidentical related donor, 4 (17%) from a matched unrelated donor, (MUD), and 2 (9%) from an unrelated cord blood donor. All patients received clofarabine. For TBI, 20 patients (87%) received a total dose of 4 Gy and 3 (13%) received 8 Gy. Fifteen patients (65%) received anti-thymocyte globulin. After a median follow-up of 22.4 months, the 2-year PFS and OS were 48% and 43%, respectively. GvHD relapse-free survival at 1 year was 22%. TRM at 100 days and 1 year after transplant were 4% and 13%, respectively. The use of clofarabine in combination with TBI as a conditioning regimen for allogeneic stem cell transplant in high-risk acute leukemia confers disease control with low transplant-related mortality.