Intensive Conditioning Regimen With Thiotepa Combined With Busulfan, Fludarabine and Cytarabine for Allogeneic Hematopoietic Stem Cell Transplantation in the Treatment of Myeloid Malignancies With Extramedullary Involvement
This study is a multicenter, single-arm, prospective phase II clinical trial that evaluates the efficacy and safety of an intensive conditioning regimen with thiotepa combined with busulfan, fludarabine, and cytarabine for allogeneic hematopoietic stem cell transplantation in the treatment of myeloid malignancies with extramedullary involvement. The conditioning regimen includes thiotepa at a dose of 5mg/kg/d from d -9 to d -8 (2 days), fludarabine at 30mg/m2/d from d -7 to d -3 (5 days), cytarabine at 1-1.5g/m2/d from d -7 to d -3 (5 days), and busulfan at 3.2mg/kg/d from d -5 to d -3 (3 days). Conditioning begins on day -9, and donor hematopoietic stem cell infusion is performed on day 0. All patients will undergo bone marrow examination on day 14 and day 28 post-transplant, followed by bone marrow examinations every 30 days within the first year after transplantation, and every 60 days within the second year after transplantation. If disease relapse is suspected during the follow-up period, bone marrow or extramedullary relapse site examinations will be conducted at any time. The primary study endpoints are the 1-year and 2-year progression-free survival (PFS) rates post-transplant. Secondary study endpoints include the incidence of acute graft-versus-host disease (GVHD) within 180 days post-transplant, cumulative relapse rates at 1 year and 2 years post-transplant, 1-year and 2-year overall survival (OS), graft-versus-host disease-free, relapse-free survival (GRFS), non-relapse mortality (NRM), cumulative incidence of chronic GVHD, and the incidence of Cytomegalovirus （CMV）and Epstein-Barr virus（EBV）reactivation within 1 year.
• Age between 18 and less than 55 years, regardless of gender.
• Criteria for myeloid tumors with extramedullary involvement:
‣ AML (Acute Myeloid Leukemia) with at least one extramedullary lesion achieving hematological remission (CR1 or CR2) after induction therapy.
⁃ MDS (Myelodysplastic Syndrome) with at least one extramedullary lesion and bone marrow blast percentage ≥ 5% achieving hematological CR after treatment; CMML (Chronic Myelomonocytic Leukemia) with at least one extramedullary lesion (diagnosed according to WHO standards) achieving hematological CR after treatment.
⁃ Control and remission of extramedullary lesions, including those in the central nervous system, testes, skin, and other extramedullary tissues.
⁃ Granulocytic sarcoma with or without bone marrow involvement, and achieving remission after treatment.
• Patients must have a suitable hematopoietic stem cell donor:
‣ Related donors must have at least 5/10 matches for HLA-A, -B, -C, -DQB1, and - DRB1.
⁃ Unrelated donors must have at least 8/10 matches for HLA-A, -B, -C, -DQB1, and
∙ DRB1.
• Hematopoietic cell transplantation comorbidity index (HCT-CI) score ≤ 2.
• ECOG (Eastern Cooperative Oncology Group) performance status: 0-2.
• Adequate liver, kidney, and cardiopulmonary function, meeting the following requirements:
‣ Serum creatinine ≤ 1.5x ULN (the upper limit of normal).
⁃ Cardiac function: Ejection fraction ≥ 50%.
⁃ Baseline oxygen saturation \> 92%.
⁃ Total bilirubin ≤ 1.5 x ULN; ALT and AST ≤ 2.0 x ULN.
⁃ Pulmonary function: DLCO (corrected for hemoglobin) ≥ 40% and FEV1 (Forced Expiratory Volume in 1 second) ≥ 50%.
• Patients must have the ability to understand and be willing to participate in this study and sign an informed consent form.