Phase 2 treosulfan/fludarabine conditioning plus PTCy alkylator-based GVHD prophylaxis in allo-HSCT.

This Phase 2, single-center study at the Masonic Cancer Center (University of Minnesota) evaluates a reduced-intensity allogeneic hematopoietic stem cell transplant approach for hematologic diseases, including AML and MDS. Patients receive treosulfan (an alkylating agent that crosslinks DNA) plus fludarabine (a purine analog that inhibits DNA synthesis), with total body irradiation added for AML/MDS per protocol, followed by infusion of stem cells from related, unrelated, or partially matched family donors. GVHD prophylaxis uses post-transplant cyclophosphamide (an alkylating agent used here to delete alloreactive T cells), plus tacrolimus (calcineurin inhibitor) and mycophenolate mofetil (IMPDH inhibitor). The core scientific/commercial angle is applying a treosulfan-based conditioning backbone with the widely adopted PTCy platform to broaden donor options while aiming to lower acute/chronic GVHD and preserve disease control. For many transplant-eligible AML/MDS patients today, care is induction/consolidation chemotherapy (and targeted agents when indicated), then allo-HSCT with busulfan- or melphalan-based conditioning and calcineurin inhibitor–based GVHD prophylaxis; this trial tests whether Treo/Flu ± TBI with PTCy can improve tolerability and GVHD outcomes without sacrificing engraftment or relapse control.