ASTA-Z 7557 impairs human natural killer (NK) cell activity

Mafosfamide (ASTA-Z 7557) is a chemotherapeutic agent currently used for purging human bone marrow cells prior to autologous bone marrow transplantation. Adoptive cell-mediated immunotherapy has been shown to have a positive effect on the control of minimal residual disease and reinduction of remission post-bone marrow transplantation. Large granular lymphocytes and natural killer (NK) cells are believed to play a role in this effect. In the present work, we assessed the effect of ASTA-Z on the cytotoxic and proliferative capabilities of large granular lymphocytes (LGLs). The ASTA-Z significantly inhibited peripheral blood and bone marrow-derived LGL proliferation and cytotoxic capabilities, while this effect was less pronounced post-IL-2 treatment. We conclude that ASTA-Z purging may significantly impair the NK cell-mediated graft versus leukemia effect and therefore should be preceded by IL-2 therapy.