Feasibility and Safety of Donor-derived NK-cell Infusions for Leukemia Relapse Prophylaxis After Hematopoietic Stem Cell Transplantation

Prior treatment

• Cellular therapy including allo-HSCT within prior 4 months period, absence of active signs of GVHD, sinusoidal obstruction syndrome, cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome.

Other illness

• Active hepatitis B, C or HIV infection.
• Uncontrolled infection; principal investigator is the final arbiter of this criterion.
• Clinical signs of grade ≥3 CNS disorders (seizure disorder, paresis, aphasia, cerebrovascular ischemia/hemorrhage, severe brain injuries, dementia, organic brain syndrome, psychosis, coordination or movement disorder).
• Mental illness of the patient or caregivers, making it impossible to realize the essence of the study and compromising compliance with medical appointments and sanitary and hygienic regime.

Other

• Inability to provide or withdrawal of written informed consent.
• Pregnant or lactating women.

• Patient (age from 14 to 25 years) and/or patient's legal representative (age from 0 to 18 years) should provide written informed consent.
• Patients with one of the following disease:
  • Acute myeloid leukemia: a. primary refractory disease (absence of complete remission (CR) after two induction regimens), b. refractory relapse (absence of CR after one salvage regimen), c. MRD-persistence before conditioning (presence of residual leukemic population more than 0,01% of bone marrow nucleated cells by flow cytometry);
  • Acute T-lymphoblastic leukemia: a. primary refractory disease (absence of complete remission (CR) after two induction regimens), b. refractory relapse (absence of CR after one salvage regimen), c. MRD-persistence before conditioning (presence of residual leukemic population more than 0,1% of bone marrow nucleated cells by flow cytometry);
  • Acute mixed phenotype leukemia: a. primary refractory disease (absence of complete remission (CR) after two induction regimens), b. refractory relapse (absence of CR after one salvage regimen), c. MRD-persistence before conditioning (presence of residual leukemic population more than 0,01% of bone marrow nucleated cells by flow cytometry).
• Patient is indicated to receive allo-HSCT according to actual clinical practice.
• Haploidentical or matched related donor was chosen and is available for allo-HSCT (and NK-cell therapy).
• Patient's clinical status: Lansky/Karnowski index ≥50%.
• Kidney function: clearance of endogenous creatinine or glomerular filtration rate according to Schwarz equation ≥50 ml/min/1,73 m2.
• Liver function: total bilirubin ≤3 ULN except for Gilbert's disease, ALT/AST ≤3 ULN.
• Heart function: left ventricular ejection fraction ≥40%.
• Lung function: lung capacity ≥50%, for children who cannot carry out of respiratory function - oxygen saturation during pulse oximetry ≥92% (without supplemental oxygen).
• Life expectancy ≥8 weeks.
• Patients who agree to long-term follow up for up to 2 years.