Introduction: We here report from an ongoing phase I/II study of HLA-haploidentical NK cell therapy to patients with high-risk myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) not eligible for standard therapies. The preparative regimen consisted of intermediate doses of Cyklophosphamide (Cy), Fludarabin (Flu) and titrated doses of total lymphoid irradiation (TLI). The trial design excluded systemic IL-2 treatment to avoid expansion of regulatory T cells and to test if in vivo expansion could be obtained without IL-2 support.

Patients:The first 12 patients were treated with Cy/Flu and an escalating dose of TLI (2 Gy and 4 Gy), followed by infusion of short-term IL-2 activated (16 hours) NK cells. Three patients received daily cyclosporine A after the conditioning. Three had relapsed, chemotherapy-refractory, primary AML, seven had secondary relapsed or refractory MDS-AML and two had high risk MDS with fibrosis.

Results: The treatment was well tolerated and no severe non-infectious toxicity could be observed in the patients. The endpoint of expansion (>100 donor NK cells/ul at day 14) was not reached, but six patients had positive microchimerism, NK cells of donor origin detectable by RT-PCR at day 7-14, that thereafter became undetectable within 7-14 days. Four of these six patients achieved complete remission (CR) whereafter they become eligible for and could proceed to allogeneic stem cell transplantation.

None of the patients with negative microchimerism obtained CR. Four patients died from progressive disease and three patients, with minor response and progressive disease, died in infections within three months of therapy.

Discussion: Although the long-term efficacy needs to be evaluated, the results suggest that a combined regimen with mild conditioning followed by NK cell therapy may induce remission in patients with chemo-refractory disease and provide a bridge to allogeneic stem cell transplantation. Notably, clinical responses were observed after only a minimal in vivo NK cell expansion and were independent on KIR-ligand mismatch.


Blomberg:VECURA: Employment. Hellström-Lindberg:Celgene: Research Funding.

Author notes


Asterisk with author names denotes non-ASH members.