Complete Remission and Signs of Immunoediting Following Haploidentical NK Cell Therapy in Refractory High-Risk MDS and AML Ell Therapy in Refractory High-Risk MDS and AML

Haploidentical IL-2-activated natural killer (NK) cells can induce remission in patients with acute myeloid leukemia (AML). Here, we report results of a phase I/II clinical trial in which short-term IL-2-activated haploidentical NK cells were given to patients with primary chemotherapy-refractory or relapsed high-risk myelodysplastic syndrome (MDS), secondary AML (MDS/AML), and AML. The patients received conditioning with cyclophosphamide/fludarabine combined with total lymphoid irradiation. To avoid expansion of regulatory T cells (Treg), no post-NK cell infusion IL-2 was given. Using this protocol, nine of sixteen patients responded. Of the nine patients, six achieved a major response with complete remission (CR), marrow CR or partial response in combination with improved hematological parameters. Five of these patients had high-risk MDS or MDS/AML, and one had relapsed de novo AML. These patients all became eligible for, and proceeded to, allogeneic hematopoetic stem cell transplantation (HSCT). Four of the patients are still free from disease >4 years after treatment. The patients with a major responses had detectable donor NK cells at days 7 to 14 following infusion, displayed reduction of allelic burden, and partial or complete eradication of MDS/AML subclones. Residual lin^-CD34⁺CD123⁺CD45RA⁺ blast cells showed an increase in total HLA class I- and HLA-E-expression suggesting immunoediting by the NK cells. Non/minor responders displayed an activation of CD4⁺ and CD8⁺ T cells as well as Treg cells accompanied by a marked increase in inflammatory cytokines. Together, this study supports the use of haploidentical NK cell infusions as a bridge to HSCT, especially for patients with high-risk MDS and MDS/AML.