High-Dose Thiotepa-Cyclophosphamide (TT/Cy) Results in Superior Outcomes Compared with Total Body Irradiation-Cyclophosphamide (TBI/Cy) in Patients with Acute Myeloid Leukemia (AML), Advanced Chronic Myeloid Leukemia (CML) and High-Grade Myelodysplasia (MDS) Undergoing Allogeneic Hematopoietic Stem Cell Transplantation (HCT)

Abstract

Background TT/Cy has been reported as a well-tolerated conditioning regimen in patients with a variety of advanced leukemias undergoing allogeneic HCT (Blood 1996, 88:353-7). While other TT-containing regimens have been investigated, outcomes with TT/Cy, specifically, in a more uniform population have not been reported. Here, we report the outcome of TT/Cy in patients with myeloid malignancies undergoing allogeneic HCT, and compare the results with TBI/Cy. Methods We retrospectively analyzed 149 consecutive patients with AML (n=101), advanced CML (n=29), and high-grade MDS with >5% blasts (n=19) who received either TBI/Cy (TBI >13.5 Gy; Cy 120 mg/kg) or TT/Cy (TT 15 mg/kg; Cy 120 mg/kg) and allogeneic HCT from HLA-matched sibling or 10/10 or 9/10 HLA-matched volunteer unrelated donors (VUD) between 2007-2016 at Indiana University. Results Sixty-seven patients received TBI/Cy and 82 received TT/Cy. Baseline characteristics were not significantly different. TBI/Cy resulted in significantly higher grades 3-4 toxicity, including mucositis (64% vs. 48%, P=0.048), acute respiratory failure (22% vs. 10%, P=0.04), transaminase elevation (24% vs. 9%, P=0.01), acute renal failure (16% vs. 5%, P=0.02), and sinusoidal obstruction syndrome (16% vs. 0%, P=0.0001). Cumulative incidence of 100-day grades 2-4 acute GVHD (TBI/Cy 15.0% ± 4.4%, TT/Cy 20.7% ± 4.5%; P=0.15) and extensive stage chronic GVHD at 1-year (TBI/Cy 35.3% ± 6%, TT/Cy 43.6% ± 5.6%; P=0.27) were not significantly different. The cumulative incidence (CI) of non-relapse mortality (NRM) was higher following TBI/Cy (Fig 1A, P 5 were both associated with a higher hazard of death (P=0.02 and P=0.004). Conclusion TT/Cy is an effective conditioning regimen in patients with myeloid malignancies undergoing allogeneic HCT and is associated with lower NRM compared with TBI/Cy. Future studies should assess whether addition of other agents to TT and Cy improve outcomes or simply increase toxicity.