Thiotepa-fludarabine-treosulfan conditioning for 2nd allogeneic HCT from an alternative unrelated donor for patients with AML: a prospective multicenter phase II trial.
Juergen FinkeClaudia SchmoorMatthias StelljesAndreas BurchertPeter DregerUte HegenbartEva-Maria Wagner-DrouetMartin BornhäuserKristina SohlbachNatalie SchubChristian ReichertsGuido KobbeBertram GlassHartmut BertzOlga GrishinaPublished in: Bone marrow transplantation (2022)
Therapeutic options for patients with AML relapsing after allogeneic HCT range from chemotherapy or hypomethylating agents with or without donor lymphocyte infusions to a 2nd allogeneic HCT. Available data are based on retrospective single center or registry studies. The aim of this multicenter trial was to investigate prospectively intensive conditioning with Thiotepa, Fludarabine and Treosulfan (TFT) for 2nd allogeneic HCT from an alternative unrelated donor in patients with AML relapse > 6 months after a 1st allogeneic HCT. Primary endpoint was disease-free survival (DFS) at one year after 2nd HCT. 50 patients median age 53.5 years, in CR/PR (34%) or active relapse (66%) were included. 33 of 38 patients (86.8%) with available data achieved CR 100 days post transplant. 23 patients were alive and free of relapse at primary endpoint one year after 2nd HCT (DFS rate 0.46, 95%-CI (0.32-0.61). Three-year rates of DFS, relapse, non-relapse mortality, and overall survival were 0.24, 95%-CI (0.13-0.36); 0.36 (0.25-0.52); 0.40 (0.29-0.57); and 0.24 (0.13-0.37). Second HCT with TFT conditioning is feasible and has high anti-leukemic efficacy in chemosensitive or refractory AML relapse after prior allogeneic HCT. Still, relapse rates and NRM after 2nd allogeneic HCT remain a challenge. The trial is registered in the German Clinical Trials Registry (number DRKS00005126).
Keyphrases
- free survival
- stem cell transplantation
- cell cycle arrest
- bone marrow
- acute myeloid leukemia
- hematopoietic stem cell
- clinical trial
- end stage renal disease
- high dose
- ejection fraction
- newly diagnosed
- prognostic factors
- peritoneal dialysis
- multiple sclerosis
- squamous cell carcinoma
- randomized controlled trial
- patient reported outcomes
- phase ii
- study protocol
- type diabetes
- low dose
- systemic lupus erythematosus
- allogeneic hematopoietic stem cell transplantation
- machine learning
- cell proliferation
- acute lymphoblastic leukemia
- radiation therapy
- peripheral blood
- data analysis