Successful Treatment of High-Risk and Refractory Acute Myeloid Leukemia with haploidentical Stem Cell Transplantation Plus NK cell therapy

Abstract 2370

Regardless of the treatment applied, the outcome for patients with refractory hematological malignancies is extremely poor. For haploidentical stem cell transplantation (haploSCT), which has been evaluated especially in high-risk AML patients lacking an HLA-identical donor, registry data show an overall survival below 10% for AML not transplanted in remission. In order to improve immune competence and to reduce the risk of relapse, we have combined the early transfer of NK cells with the haploSCT approach. PATIENTS AND METHODS: Twenty-five patients (AML = 16, ALL = 5, CML = 2, Hodgkin = 1, MDS = 1) received a haploSCT followed by transfer of purified CD56+CD3-NK cells at day +2. Conditioning consisted of total body irradiation, thiotepa, fludarabine, and OKT3. NK cells were isolated from the CD34- fraction using an automated two-step procedure of CD3+ depletion and subsequent CD56+ selection. No other immunosuppression was routinely delivered. RESULTS: Patients received a mean of 13.3 × 10⁶ CD34+ cells/kg (range 6.12–26.97) with 2.89 × 10⁴/kg (0.95-7.4) contaminating CD3+ cells. A mean of 9.8 × 10⁶ CD56+CD3- NK cells/kg (range 1.61–32.2) was adoptively transferred. Most of the patients developed early GVHD of the skin (median onset day=12), which promptly resolved after short term treatment with steroids and CSA. The main cause of death consisted of infections (n = 10), chronic GvHD (n= 2), and relapse (n = 4). After a median follow-up of 1442 days (3.9 years) (range 0.1 to 7.1 years) 9 of 25 patients are alive and in complete remission resulting in a 2-year overall survival (OS) estimate of 29%. Out of 16 high-risk patients with AML, 10 had refractory or active disease prior to transplantation. For a matched pair analysis, these patients were matched for age, disease status, conditioning regimen and year of transplantation using the EBMT database. AML patients treated with haploSCT plus NK cell transfer had a superior 2-year overall survival (40 vs 11%, 95% CI) in comparison to matched controls with haploSCT only (p=0.02) CONCLUSIONS: HaploSCT plus NK cells is feasible and shows promising survival rates for a group of patients lacking other treatment options. Best results were achieved in patients with AML not only in remission but also with refractory disease.