title: ASTA-Z 7557 impairs human natural killer (NK) cell activity.
abstract: 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.
authors.affiliation: Department of Bone Marrow Transplantation, Cancer Immunobiology Research Laboratory, Hadassah Univeristy Hospital, Jerusalem, Israel.
authors.forename: R
authors.initials: R
authors.lastname: Condiotti
authors.forename: S
authors.initials: S
authors.lastname: Slavin
authors.forename: A
authors.initials: A
authors.lastname: Nagler
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D016465:Bone Marrow Purging; D002455:Cell Division / Q000187:drug effects; D003520:Cyclophosphamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects* / Q000276:immunology
chemical_list: D000970:Antineoplastic Agents; D007376:Interleukin-2; C048341:mafosfamide; D003520:Cyclophosphamide