Clinical Implications of Killer Cell Immunoglobulin-Like Receptor (KIR) Genotypes on Autologous Peripheral Blood Stem Cell Transplantation for Acute Myelogenous Leukemia Patients.

Natural killer (NK) cell alloreactivity after allogeneic hematopoietic stem cell transplantation (HSCT) in various settings is introduced by the regulatory role of killer cell immunoglobulin-like receptors (KIR). However, no influence of NK cells on relapse or survival after autologous HSCT for patients with acute myelogenous leukemia (AML) has been demonstrated. Since it is still debated whether autologous NK cells are involved in the eradication of leukemia cells, we evaluated the role of NK cells as a susceptibility factor for long-term survival. All 67 enrolled patients who received autologous HSCT were typed for the presence or absence of 19 different KIR genes and pseudogenes using a polymerase chain reaction-based sequence-specific primer method with the Pel-Freez kit, according to the manufacturer’s protocol (Invitrogen, Carlsbad, CA). The median follow-up was 21 months (range 2–55). All patients were in first complete remission (CR), as assessed immediately before the elective transplantation. The median age of the enrolled patients was 42 years (range 16–68). There were 33 females and 34 males. All patients received our modified TAM conditioning, which consisted of fractionated total body irradiation (12 Gy, five fractions in 3 days) from day −8 to −6, followed by intermediate-dose cytarabine (Ara-C; 1.5 g/m² over 3 h every 12 h for six doses) from day −5 to −3, and melphalan (100 mg/m² over 30 min) on day −2 only. The peripheral blood stem cells were collected after administering granulocyte colony-stimulating factor, following consolidation chemotherapy. The patients had 7–13 KIR genes, which is similar to the range in the normal population. The median infused cell dose was 4.2 × 10⁶/kg (range 1.7–6.3) CD34+ cells. Fifty patients were alive (75%). Of the 67 patients, 43 were in continuous CR (64%) and 14 died in relapse (21%), while 3 (4%) died due to non-relapse causes. The Kaplan-Meier estimated 4-year disease-free survival (DFS) rate was 55% (95% CI 47–62%). We evaluated whether the presence or absence of any single or combination of inhibitory or activating KIR genes in the patients affected DFS and eventfree survival (EFS). The presence of an activating KIR 2DS1 gene was critical for the DFS and EFS, as shown in a previous study of allogeneic HSCT (Kim et al., Transplantation 2007). Additionally, the presence of two activating genes in the combinations 2DS3-2DS4*003 or 2DS4*003-2DS5 tended to be associated with DFS (P=0.0866). Since our findings are based on a single disease entity, i.e., adult AML, they suggest that the presence of activating KIR genes may, at least in some ways, be critical for autologous NK immunomodulation to influence the anti-leukemic effects, especially considering the impact of activating KIR genotypes on long-term survival.