Thiotepa/cyclophosphamide (TT/Cy) preparative regimen for patients with acute lymphoblastic leukemia (ALL) undergoing allogeneic stem cell transplantation.

6556 Background: Total body irradiation (TBI)-based preparative regimens have been standard for patients with ALL undergoing allogeneic stem cell transplant (SCT). It is unclear if chemotherapy-only regimens are equally efficacious. Here, we present the largest reported experience with myeloablative TT/Cy in patients with ALL undergoing allogeneic SCT and compare outcomes with TBI-based regimens. Methods: Patients with ALL receiving myeloablative allogeneic SCT at Indiana University from 2007-2020 were included. TT/Cy consisted of TT 15 mg/kg and Cy 120 mg/kg. TBI/Cy consisted of 13.2 Gy in 8 fractions and Cy 3600 mg/m 2 or etoposide 60 mg/kg. The primary endpoint was overall survival (OS). Secondary endpoints included relapse-free survival (RFS), engraftment, and toxicities within the first 100 days. Median follow up for surviving patients is 2,532 (range 599-4,762) days. Results: 80 patients with ALL of median age 40 (range 22-59 years) received conditioning with TT/Cy (n=25) versus TBI/Cy or TBI/etoposide (n=55). Baseline characteristics were similar. For patients receiving TT/Cy, the median OS was not reached, and the 4-year OS was 54.5% (95% confidence interval CI, 34.3-74.7%), compared with a median OS of 1,491 days and a 4-year OS of 50.9% (95% CI, 37.8-64.2%) for those receiving TBI-based conditioning (p=.75). Similarly, for TT/Cy patients, the median RFS was 847 days and 4-year RFS was 43.2% (95% CI, 23.4-63%), not significantly different from median RFS of 1491 days and 4-year RFS 50.2% (95% CI 36.9-63.5; p=.232) for recipients of TBI regimens. On multivariable analysis, only a higher disease risk index was associated with significantly worse OS (p<.001), while conditioning regimen was not predictive of OS. Similarly, there was no significant difference in RFS between TT/Cy and TBI-based regimens on either univariable or multivariable analysis. Secondary endpoints are summarized in the table. As shown, TT/Cy was associated with significantly lower incidence of mucositis, TPN usage, bacterial infection, sinusoidal obstruction syndrome (SOS), and longer length of stay of primary transplant admission. Conclusions: While there was no significant difference in OS or RFS for patients receiving either TT/Cy or TBI-based conditioning, TBI was associated with greater toxicity. Our data suggests that TT/Cy is an acceptable alternative to TBI-based conditioning for ALL patients undergoing myeloablative allogeneic SCT. Table: see text