Sorafenib Relapase Prophylaxis After HCT With PTBCy Regimen

Prior treatment

• successfully treated relapse between transplantation and enrollment
• Second malignancy not in complete remission within 6 months prior to randomization

Other illness

• Stroke within 3 months of inclusion, unless related to the underlying malignancy
• Uncontrolled bacterial or fungal infection at the time of enrollment defined by CRP\> 70 mg/L
• Somatic or psychiatric disorder making the patient unable to sign informed consent

Lab values

• donor lymphocyte infusion prior to randomization
• Moderate or severe cardiac disease: ejection fraction \<50%, unstable angina, stable angina NYHA class III or IV, chronic heart failure NYHA class III or IV, Lawn grade V arrhythmia, myocardial infarction within 3 months before inclusion
• Severe organ dysfunction: AST or ALT \>10 upper normal limits, bilirubin \>2 upper normal limits, creatinine \>2 upper normal limits
• Creatinine clearance \< 30 mL/min

Other

• use of any other planned method for prophylaxis of relapse besides sorafenib
• Severe decrease in pulmonary function: FEV1 \<50% or DLCO\<50% of predicted or respiratory distress or need for oxygen support;
• Requirement for vasopressor support at the time of enrollment
• Requirement for positive-pressure oxygen at the time of enrollment
• Karnofsky index \<30%
• Pregnancy

• Patients must undergo allogeneic hematopoietic stem cell transplantation with post-transplantation bendamustine AND cyclophosphamide from any donor.
• Patients must have high-risk myeloid malignancy as an indication for transplantation defined as:
  • acute myeloid leukemia not in hematological remission prior to transplantation,
  • ≥ 3 remission of acute myeloid leukemia,
  • any myeloid malignancy with bi-allelic tp53 mutation,
  • any myeloid malignancy with complex karyotype,
  • therapy-related myeloid malignancy not in MRD-negative response
  • myelodysplastic syndrome with very high IPSS-R risk
  • any myeloid malignancy with monosomal or t(3;3) karyotype,
  • any myeloid malignancy with ASXL1, bi-allelic tp53 or RUNX1 mutation, EVI1 overexpression
  • MDS/NPM unclassified not in hematologic remission.
• Documented hematological remission in the bone marrow at the time of inclusion post-engraftment, measurable residual disease is allowed
• First 100 days after allogeneic hematopoietic stem cell transplantation