Early engraftment and immune kinetics following allogeneic transplant using a novel reduced-toxicity transplant strategy in children/adolescents with high-risk transfusion-dependent thalassemia: Early results of the ThalFAbS trial.

Background: Allogeneic transplant for patients with transfusion-dependent thalassemia is challenging once there has been iron overload and chronic transfusion support.

Objective(s): A transplant strategy that reduced intensity of the preparative regimen and tailored immunosuppression to both support donor engraftment and prevent GVHD was developed for this population. The combination of a pretransplant immunosuppression phase with reduced dosing of fludarabine/prednisone, treosulfan-based preparative regimen with reduced cyclophosphamide dosing, and introduction of a calcineurin/methotrexate-free GVHD prophylaxis/engraftment supporting regimen with abatacept/sirolimus/ATG was tested.

Study Design: The ThalFAbS trial was a prospective pilot trial (NCT05426252) of a transplant strategy designed for higher risk patients with transfusion-dependent thalassemia treated 12 pediatric patients (4 alpha thalassemia, 8 beta thalassemia). Descriptive statistics were used to characterize transplant outcomes and immune recovery.

Results: With a median follow-up of 12 months (range 4-26 months) post-transplant, the first 12 patients all had prompt and durable trilineage donor engraftment with low transplant-related morbidity and acute GVHD and are alive without transfusion support. GVHD was limited to one patient with grade 2 skin only acute GVHD and 3 patients with limited oral chronic GVHD. Early hematologic and immunologic recovery was achieved with low transfusion support and infection rates. Neutrophil recovery occurred at a median of 18 d (range 15-24 d) and platelet recovery at 18 d (range 12-36 d). None of the patients had VOD, TA-TMA, sepsis. This platform was sufficient to support haploidentical donor transplant in 2 patients.

Conclusion(s): The ThalFAbS approach is tailored to meet the unique needs of transfusion-dependent thalassemia patients. Delivery of this novel regimen is feasible and shows excellent early engraftment and transplant outcomes. Further follow-up of this cohort and expansion of patient numbers is needed before generalization but early experience is promising.