Basiliximab in the Prevention of aGVHD for Unrelated Donor Hematopoietic Stem Cell Transplantation in Patients with Thalassemia Major: A Prospective, Multicenter, Open-Label, Randomized Controlled Study

Background: Hematopoietic stem cell transplantation (HSCT) is currently the only clinical cure for thalassemia major (TM). Graft-versus-host disease (GVHD) and transplant-related mortality (TRM) remain major barriers to clinical outcomes in TM-unrelated donor transplantation (MUD-HSCT).

Aims: The role of Basiliximab in preventing acute graft-versus-host disease (aGVHD) after MUD-HSCT in thalassemia major (TM) is still unknown. We performed a prospective, multicenter, open-label, randomized controlled trial (RCT). The study is registered at www.clinicaltrials.gov as #NCT02342145.

PATIENTS AND METHODS: Patients with TM with unrelated donor were randomly assigned to a basiliximab group (20 mg/kg basiliximab on days 0 and +4, respectively, plus tacrolimus [FK506], methotrexate [MTX], and mycophenolate mofetil [MMF]) and a control group (FK506, MTX, and MMF). The primary end point of this study was grade 2-4 aGVHD on day 100.

Results: From April 2015 and September 2021, a total of 205 TM patients were enrolled. The ratio of male to female was 123 to 82 with a median age of 7 years (range, 2-19 years). Patients were randomly assigned to the basiliximab group of 102 and the control group of 103. Comparison of the basiliximab group and the control group, the cumulative incidence rate of grade 2-4 aGVHD was 24.5% and 29.1%, respectively (P=0.456), and the cumulative incidence rate of grade 3-4 aGVHD was 8.8% and 14.6% (P=0.201); the cumulative incidence rate of moderate or severe chronic GVHD was both 2.9%; median days of neutrophil engraftment were +11.8 and +11.6 days, respectively (P=0.701), platelets Implantation days were +15.4 and +13.5 days (P=0.126); TRM was 3.6% and 7.1% (P=0.249), over survival (OS) was 96.4% and 92.0% (P=0.188), respectively and thalassemia-free survival (TFS) of the two groups was also the same as the OS. There was no significant difference between the basiliximab and control groups with regard to cytomegalovirus reactivation, Epstein-Barr virus reactivation, and transplant-related complications. Subgroup analysis according to the degree of HLA matching showed that the 9/10 mismatch group had significantly lower OS and TFS than the 10/10 matched group (both 82.6% v 96.5%, P=0.004). The 3-year OS and TFS of the entire cohort (205 TM patients ) were 94.1% and 94.0%, respectively(Table 1, Fig 1).

CONCLUSION: This first prospective randomized study showed basiliximab at a dose of 20 mg on day 0 and day+ 4 did not reduced the incidence of both aGVHD and cGVHD in patients with TM after MUD-HSCT. The incidence of aGVHD in unrelated donor transplants for TM patients is still high, 9/10 mismatched unrelated donor transplants had poor result when comparing 10/10 matched donor transplants for TM patients. Unrelated donors are still a very good alternative source of donors. The TFS of TM patients treated by unrelated donor transplantation can reach 94.0%.

No relevant conflicts of interest to declare.