Randomized Study of Conditioning of Fludarabine Combined With Single or Dual Alkylating Agents in Myeloid Malignancies

Fludarabine and busulfan was considered as myeloablative but reduced toxicity regimen and became as the mainstay of conditioning regimen for adult patients with acute myeloid leukemia (AML) or myelodysplasia syndrome (MDS). The disease relapse remained as major cause of treatment failure. In general, the cumulated incidence of relapse (CIR) is about 15\~20% dependent on the risk of patients undergoing allogeneic stem cell transplantation (allo-HSCT). Conditioning regimen with dual alkylating agents such as fludarabine, busulfan and thiotepa (TBF) showed decreased risk of relapse in myeloid malignancies. More recently, the investigators demonstrated that conditioning regimen with dual alkylating agents consistent of fludarabine, busulfan and melphalan could achieve a low incidence of relapse (2 year CIR <10%). In this multiple-center randomize study, the aim is to compare the transplantation outcome in adult patients with AML/MDS undergoing allo-HSCT with conditioning regimen of Flu-Bu vs. Flu-Bu-Mel.

• Fludarabine, busulfan and melphalan (Drug): FLudarabine 150mg/m2 + Busulfan 6.4mg.kg + Mel 140mg/m2
• Fludarabine and Busulfan (Drug): FLudarabine 150mg/m2 + Busulfan 12.8mg.kg

Primary outcomes

• disease-free survival [2 year]: event defined as relapse and death of any causes

Secondary outcomes

• overall survival [2 year]: event defined as death of any causes
• incidence of relapse [2 year]: event defined as disease relapse (bone marrow or extra medullary)
• non relapse mortality [day 100]: event defined as death without disease relapse
• non relapse mortality [2 year]: event defined as death without disease relapse

Sex: All, ages: 16 Years to 55 Years

Inclusion Criteria:

* acute myeloid leukemia (acute promyelocytic leukemia excluded) in 1st complete remission
* myelodysplasia syndrome with bone marrow blast >5% and remaining less than 20% at transplantation
* patients with HLA matched sibling donor, 9-10 matched unrelated donor or haplo-identical related donors
* inform consent provided

Exclusion Criteria:

* AML patients with active CNS or extramedullary diseases
* patients with active viral, bacterial or fungal infection
* patients with hepatitis B virus >1X103 copy/ml
* patients with abnormal liver function, renal function, respiratory or cardiac dysfunction
* patients with uncontrolled mental disorders
* patients with HIV

• Chun Wang, Principal investigator, Go Broad Health Center, Zhaxin Hospital