Favorable response of early stage B CLL patients to treatment with IFN-alpha 2.
Since interferon (IFN-alpha) treatment has proven effective in hairy cell leukemia, its evaluation in chronic lymphocytic leukemia (CLL), a cytologically related disease, appeared reasonable. In our study, we have focused on previously untreated, early stage patients who are less than 60 years of age. All patients had less than 50,000 lymphocytes/microL and immunologic analysis revealed a CD20+, IgM+, IgD- phenotype for leukemic B cells in eight of nine patients. Recombinant interferon alpha 2b (IFN-alpha 2) at 5 x 10(6) U was given subcutaneously three times per week for 8 to 16 months. Consistent with earlier reports, side effects were minor with this low-dose protocol. All patients responded with a decrease of WBC count and lymphocyte count; in one patient, splenomegaly resolved such that he moved from Rai stage II to Rai stage I. On the average CD20+ B cells decreased from 14,312 to 3,995 cells/microL, indicating that no complete eradication of the leukemic cells was possible. A partial response, based on a greater than 50% reduction of CD20+ B cells was obtained in five of seven patients analyzed. The increased numbers of CD2+ T lymphocytes decreased in response to interferon treatment in six of seven patients. Furthermore, in a portion of the patients class II antigen expression was enhanced on LeuM3+ monocytes suggesting an in vivo activation of the monocytes by IFN-alpha 2. Immunoglobulin levels were substantially improved in that serum IgG increased by more than 3 g/L in three of seven patients. In one patient, lymphocyte counts increased in spite of continued therapy, whereas all others exhibited no increase of lymphocyte numbers while on therapy. Our study clearly demonstrates effects of IFN-alpha 2 treatment on both the leukemic cells and on the nonleukemic components of the immune system in peripheral blood. Whether IFN-alpha treatment will result in long-term beneficial effects in early stage CLL needs to be evaluated in a larger study.
Ziegler-Heitbrock
H W
HW
Institute for Immunology, University of Munich, FRG.
Schlag
R
R
Flieger
D
D
Thiel
E
E
D000943:Antigens, Differentiation / Q000032:analysis; D006681:HLA-D Antigens / Q000032:analysis; D006801:Humans; D007132:Immunoglobulin Isotypes / Q000032:analysis; D007370:Interferon Type I / Q000627:therapeutic use*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000628:therapy*; D007958:Leukocyte Count; D007963:Leukocytes, Mononuclear / Q000032:analysis; D011994:Recombinant Proteins
D000943:Antigens, Differentiation; D006681:HLA-D Antigens; D007132:Immunoglobulin Isotypes; D007370:Interferon Type I; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins