Haploidentical Stem Cell Transplant With or Without NK Cell Infusion in AML and MDS (Bigeminy)

Haploidentical Stem Cell Transplantation With or Without NK Cell Infusion in Refractory/Relapsed Acute Myeloid Leukemia and Myelodysplastic Syndrome:The BigEMINy Study

Relapse after an allogeneic hematopoietic stem cell transplantation (HSCT) is high in patients with advanced AML, in the 50% range. NK cells have been shown to possess significant anti-leukemic activity and may be used to reduce the incidence of relapse in patients with advanced AML. Investigators hypothesize that the administration of a purified boost of NK cells on day +7 post HSCT, will reduce the incidence of relapse from the current 50% to 25%. In a phase III multicenter clinical study, 116 patients will be randomized to receive or not a boost of donor NK cells on day +7 post-HSCT. The first 10 patients in the experimental arm will be analyzed for toxicity. The stopping rule will be a transplant related mortality of more than 50% in the first 20 patients who received NK cells.

Haplo stem cell transplant (from bone marrow or apheresis) is followed by a haplo-NK cell infusion (target dose ≥1*106/kg b.w.) at day 7. Unstimulated haplo-NK cells are collected through apheresis Mononuclear cells are then subjected to a preliminary negative selection of CD3+ cells and to a subsequent positive selection of CD56+ cells. CD3 negative/CD56 positive cells are infused

Patients in this arm receive standard haplo stem cell transplant (from bone marrow or apheresis) transplant without subsequent NK cell infusion.

Patients in this arm receive haplo-SCT followed by one boost of NK cells one/two weeks after the transplant. Lymphocyte are collected by apheresis from the donor one-two weeks after BM harvest. CD3 negative/CD56 positive cells are selected by immunomagnetic columns (other lymphocytes are stored to be used as DLI)

Patients in this arm receive a standard haplo-SCT. All administerd therapies are the same as in other arm, except for the NK cell boost..

Inclusion Criteria: Diagnosis of AML or MDS Patients not in remission at the time of transplant Age 18-75 ECOG performance status <2 Availability of a family HLA haploidentical donor, eligible to donate both marrow cells and unstimulated lymphocytes (1 apheresis procedure at day +7) . Exclusion Criteria: Positive serologic markers for human immunodeficiency virus (HIV) Acute hepatitis B virus (HBV) or acute hepatitis C virus (HCV) infection