title: Immunomodulation of early engrafted natural killer cells with interleukin-2 and interferon-alpha in autologous stem cell transplantation.
abstract: High relapse rates during the first year after autologous stem cell transplantation (ASCT) for multiple myeloma or non-Hodgkin lymphoma are due to the failure of high-dose chemotherapy to eradicate minimal residual disease. Post-ASCT immunorecovery studies have shown that quantities of natural killer (NK) cells return to normal within 1 month post-ASCT in contrast to the recovery of T and B cell populations (up to 1 year). Preclinical studies have demonstrated that NK cells have potent antitumor activity. IL-2 and IFN-alpha enhance NK-cell activity. We investigated the efficacy of IL-2 and IFN-alpha to up-regulate NK-cell cytotoxicity at 14 days post ASCT. Twenty patients undergoing ASCT had PBMCs collected pretransplantation and at 14 days post transplantation. PBMCs (effector cells) from each blood sample were incubated in vitro with IFN-alpha and IL-2 at 10000 IU/ml. NK cell activity was determined by sodium chromate (51)Cr release assay for lysis of K562 target cells. IL-2 and IFN-alpha each increased lysis of K562 cells compared with placebo (effector-to-target ratio, 50:1, P < 0.001). Increased NK cell activity occurred in samples from all patients. IL-2 and IFN-alpha up-regulated NK cell activity at 14 days post ASCT. They may be useful as immunomodulators as early as 14 days post ASCT to eradicate or control minimal residual disease.
authors.affiliation: Division of Hematology and Internal Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
authors.forename: L F
authors.initials: LF
authors.lastname: Porrata
authors.forename: D J
authors.initials: DJ
authors.lastname: Inwards
authors.forename: M Q
authors.initials: MQ
authors.lastname: Lacy
authors.forename: S N
authors.initials: SN
authors.lastname: Markovic
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D000477:Alkylating Agents / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D002330:Carmustine / Q000008:administration & dosage / Q000494:pharmacology; D002478:Cells, Cultured / Q000187:drug effects; D003561:Cytarabine / Q000008:administration & dosage / Q000494:pharmacology; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D016130:Immunophenotyping; D016898:Interferon-alpha / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology*; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000637:transplantation; D018655:Lymphocyte Count; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy / Q000276:immunology / Q000628:therapy; D008297:Male; D008558:Melphalan / Q000008:administration & dosage / Q000494:pharmacology; D008875:Middle Aged; D009101:Multiple Myeloma / Q000276:immunology / Q000628:therapy; D011034:Podophyllotoxin / Q000008:administration & dosage / Q000494:pharmacology; D013997:Time Factors; D019172:Transplantation Conditioning; D014182:Transplantation, Autologous
chemical_list: D000276:Adjuvants, Immunologic; D000477:Alkylating Agents; D016898:Interferon-alpha; D007376:Interleukin-2; D003561:Cytarabine; D011034:Podophyllotoxin; D008558:Melphalan; D002330:Carmustine