Donor-Derived Ex-Vivo Expanded Natural Killer Cell Infusions in Children and Young Adults With High Risk Acute Myeloid Leukemia Receiving Myeloablative HLA-Haploidentical Hematopoietic Cell Transplant

Prior treatment

• Inability to comply with medical therapy or follow-up
• Prior allogeneic transplant

Other illness

• Active extramedullary disease
• Unresolved/ongoing and serious viral, bacterial, or fungal infection despite appropriate treatment
• Patients with Fanconi Anemia and Down syndrome

Other

• Positive pregnancy test in a female of child-bearing potential (FCBP)

• Age ≤ 25 years at time of enrollment
• High-risk AML, as defined by one of the following:
• AML in CR1 (defined as \<5% blasts in BM by morphology and flow cytometry) having at least one of these high-risk features:
• Mutations associated with high risk disease (Appendix A). Other high-risk features not explicitly stated in Appendix A can be considered after discussion/approval with the protocol chair/team
• MRD-positive at the end of Induction I chemotherapy (defined as flow cytometry ≥ 0.1% blasts)
• AML in ≥CR2 (defined by \<5% blasts in BM by morphology and flow cytometry)
• Recovery from prior cycle of chemotherapy as defined by an absolute neutrophil count ≥ 500/mm3
• AML secondary to select germline marrow failure disorders (with exception of Fanconi Anemia) may be eligible but require approval from Protocol Chairs prior to enrollment.
• Performance status ≥70% (Lansky for \<16 years; Karnofsky for ≥16 years)
• Adequate major organ system function as demonstrated by:
• Renal: Creatinine clearance (CrCl) ≥60 mL/min/1.73m2 by Cockcroft-Gault formula, Schwartz formula, or nuclear GFR study (Table 3)
• Hepatic: Total bilirubin \<2 mg/dL (unless due to Gilbert syndrome) and ALT and AST \< 5x ULN
• Cardiac: LVEF at rest ≥50% or SF ≥27% (by MUGA or ECHO)
• Pulmonary: DLCO, FEV1, and FVC ≥ 50% of predicted corrected for hemoglobin. For patients \<7 years of age or those unable to perform PFTs: O2 Sat \>92% on room air by pulse oximetry and on no supplemental O2 at rest
• The patient, patient's parent, guardian, or legal representative can provide written informed consent