IFN-beta induced biochemical and immunological modifications in hairy cell leukemia patients.
BACKGROUND
Although IFN-beta is 30-40% homologous with IFN-alpha, its intrinsic biological properties are not identical. Compared with IFN-alpha, IFN-beta exerts greater in vitro antiproliferative activity on many cell lines, stimulates peripheral blood stem cells of hairy-cell leukemia (HCL) patients to differentiate to erythroid burst forming cells, has higher specific type I IFN receptor affinity and modulates the expression of class II histocompatibility antigens. IFN-beta would, therefore, be expected to have a greater, or at least similar, antitumor activity as that of the various types of IFN-alpha.


METHODS
We have treated 12 patients affected by HCL with IFN-beta and have investigated the biological and immunological changes induced by such treatment.


RESULTS
A rise in beta 2-microglobulin and neopterin values throughout IFN-beta therapy was documented in most patients. An increase in NK activity was observed only in clinical responders whose CD57+/CD16+ cell ratio dropped below baseline. There was also a modulation in IFN-gamma synthesis that was dependent on baseline levels and in line with the clinical response. IFN-beta provoked a reduction in CD3+ and CD4+ cell subsets in patients with WBC greater than or equal to 10.0 x 10(9)/1 and greater than or equal to 50% circulating HCs, an expansion in absolute number of CD3+ and CD8+ cell fractions and a slight rise in the absolute values of CD2+ and CD4+ cell subpopulations in patients with WBC less than or equal to 5.0 x 10(9)/1 and less than or equal to 50% circulating HCs. There was no correlation between either the IFN-beta induced increase in beta 2-M or Np levels and clinical response. Most immunological parameters improved or normalized later during the course of IFN-beta treatment, when pathological-hematological signs of disease remission were already evident.


CONCLUSIONS
The relevance of the IFN-beta induced changes as well as that of the IFN-alpha induced biological effects in the clinical control of HCL remain unclear.
Liberati
A M
AM
Clinica Medica I, Università degli Studi di Perugia, Italy.
Schippa
M
M
Portuesi
M G
MG
Grazia Proietti
M
M
De Angelis
V
V
Ferrajoli
A
A
Cinieri
S
S
Di Clemente
F
F
Palmisano
L
L
Berruto
P
P
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D000951:Antigens, Neoplasm / Q000032:analysis; D001708:Biopterins / Q000031:analogs & derivatives / Q000096:biosynthesis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use*; D016899:Interferon-beta / Q000494:pharmacology / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000473:pathology; D007943:Leukemia, Hairy Cell / Q000097:blood / Q000276:immunology / Q000628:therapy*; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis; D019798:Neopterin; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001613:beta 2-Microglobulin / Q000096:biosynthesis
D015703:Antigens, CD; D000951:Antigens, Neoplasm; D007155:Immunologic Factors; D009363:Neoplasm Proteins; D001613:beta 2-Microglobulin; D001708:Biopterins; D019798:Neopterin; D016899:Interferon-beta; D007371:Interferon-gamma