Phenotypic and functional analysis of peripheral blood lymphocytes during interferon-alpha 2b therapy in multiple myeloma patients with low tumor mass.
BACKGROUND
IFN-alpha has recently been shown to prolong the remission phase in MM patients with low tumor mass. So far, it is not known whether IFN-alpha exerts its effect directly on the myeloma cells or is mediated by modulation of the host response.


METHODS
The immune status of 12 multiple myeloma patients with low tumor mass (10 in remission phase, 2 with stage IA disease) was investigated by phenotypic and functional analyses before, after 3, and after 6 months of recombinant interferon-alpha 2b (IFN-alpha) therapy.


RESULTS
Phenotyping of peripheral blood lymphocytes (PBL) revealed a significant decrease of HLA-DR+ (P = 0.01) and CD20+ (P = 0.04) cells after 6 months of therapy. Two-color phenotyping of purified T cell populations (PBT) showed a significant increase of CD4+ CD11b+ cells (P = 0.01) after 6 months of therapy. Functional analyses were carried out on PBL (NK cell-mediated cytotoxicity) and PBT (alloreactive cytotoxicity, CTL; IL2-induced cytotoxicity, LAK activity). NK and CTL activities were poorly influenced by IFN-alpha treatment, whereas LAK activity showed a significant increase (P = 0.007). Any significant association between these immunological changes and the disease status was questioned by the lack of differences between MM in relapse and MM with stable disease at the sixth month of IFN-alpha therapy.


CONCLUSIONS
i) IFN-alpha in MM with low tumor mass may exert its therapeutic activity by directly acting on the tumor cells; ii) the parameters which have been used in this study are not appropriate to monitor the immunological effects (if any) of IFN-alpha therapy.
Bianchi
A
A
Dipartimento di Medicina, Ospedale Molinette, Torino, Italy.
Omedé
P
P
Attisano
C
C
Camponi
A
A
Dianzani
U
U
Boccadoro
M
M
Pileri
A
A
Massaia
M
M
D015703:Antigens, CD / Q000032:analysis; D000951:Antigens, Neoplasm / Q000032:analysis; D006684:HLA-DR Antigens / Q000032:analysis; D007111:Immunity, Cellular; D007155:Immunologic Factors / Q000627:therapeutic use*; D016130:Immunophenotyping; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D015979:Killer Cells, Lymphokine-Activated / Q000473:pathology; D007694:Killer Cells, Natural / Q000473:pathology; D007958:Leukocyte Count; D009101:Multiple Myeloma / Q000097:blood / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D014411:Neoplastic Stem Cells / Q000473:pathology; D011994:Recombinant Proteins; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000473:pathology*; D013997:Time Factors
D015703:Antigens, CD; D000951:Antigens, Neoplasm; D006684:HLA-DR Antigens; D007155:Immunologic Factors; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins