Low Dose Decitabine + Modified BUCY Conditioning Regimen for High Risk Acute Myeloid Leukemia Undergoing Allo-HSCT

Allo-HSCT is the most effective treatment stratagey for high risk acute myeloid leukemia. At present, modified BUCY is the standard conditioning regimen for AML undergoing allo-HSCT in our institute. However, relapse occured in as high as 30-50% high risk AML patients after allo-HSCT. Thus, the best conditioning regimen for this subgroup remains to be optimized. Low dose decitabine in combination with chemotherapy have been shown to improve comple remission rate of high risk AML patients. To reduce the relapse rate after allo-HSCT, low dose decitabine is added in the modified BUCY regimen. In this study, the safety and efficacy of low dose decitabine + modified BUCY vs modified BUCY myeloablative conditioning regimens in high risk undergoing allo-HSCT are evaluated.

• Decitabine plus Modified BUCY (Drug): Decitabine:20 mg/m²/day on day -14 to -10; Modified BUCY: 1. Sibling:semustine 250 mg/m²/day on day -9;cytarabine 2 g/m²/day on day -8；busulfan 3.2mg/kg/day on day -7 to -5;cyclophosphamide 1.8g/m²/day on day -4 to -3. 2. Unrelated:semustine 250 mg/m²/day on day -10;cytarabine 2 g/m²/day on day -9 to -8；busulfan 3.2mg/kg/day on day -7 to -5;cyclophosphamide 1.8g/m²/day on day -4 to -3. 3. Haploidentical:semustine 250 mg/m²/day on day -10;cytarabine 4 g/m²/day on day -9 to -8；busulfan 3.2mg/kg/day on day -7 to -5;cyclophosphamide 1.8g/m²/day on day -4 to -3.
• Modified BUCY (Drug): 1. Sibling:semustine 250 mg/m²/day on day -9;cytarabine 2 g/m²/day on day -8；busulfan 3.2mg/kg/day on day -7 to -5;cyclophosphamide 1.8g/m²/day on day -4 to -3. 2. Unrelated:semustine 250 mg/m²/day on day -10;cytarabine 2 g/m²/day on day -9 to -8；busulfan 3.2mg/kg/day on day -7 to -5;cyclophosphamide 1.8g/m²/day on day -4 to -3. 3. Haploidentical:semustine 250 mg/m²/day on day -10;cytarabine 4 g/m²/day on day -9 to -8；busulfan 3.2mg/kg/day on day -7 to -5;cyclophosphamide 1.8g/m²/day on day -4 to -3.

Primary outcomes

• disease-free survival (DFS) [3 year]: time from randomization to the first of reccurrence or death
• overall survival (OS) [3 year]: time from randomization to death from any cause

Secondary outcomes

• veno-occlusive disease (VOD) [3 year]: incidence of veno-occlusive disease (VOD) events
• graft-versus-host disease (GvHD) [3 year]: incidence and severity of acute (aGvHD) and chronic graft-versus-host disease (cGvHD)
• transplant related mortality （TRM） [3 year]: cumulative incidence of transplant related mortality
• relapse [3 year]: cumulative incidence of relapse

Sex: All, ages: 12 Years to 60 Years

Inclusion Criteria:

* Age 12 to 60 years.
* Diagnosis of high-risk acute myeloid leukemia at the time of transplant. ("High-risk" AML features are defined by the following: relapsed or primary refractory AML; Secondary AML（AML Secondary to myelodysplastic syndrome(MDS) or treatment-related AML); extramedullary leukemia; adverse cytogenetic abnormalities of monosomy 5, monosomy 7, or deletion of 5q; or presence of FLT3 positive internal tandem duplication (FLT3/ITD+), particularly high allelic ratio.)
* Patient must have adequate pre-transplant organ function.

Exclusion Criteria:

* Age <12 or >60 years.
* Uncontrolled bacterial, viral, fungal, or other infection before conditioning regimen.
* Any other severe concurrent diseases, or have a history of serious organ dysfunction.
* Pregnant or lactating females.

• Depei Wu, MD, Principal investigator, The First Affiliated Hospital of Soochow University