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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Annals of hematology 70 (1995), S. 113-120 
    ISSN: 1432-0584
    Keywords: Key words CML ; IFN alpha ; Bone marrow transplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The aim of this review is to summarize the current knowledge on the clinical results of biotherapy of chronic myelogenous leukemia (CML) and potential mechanisms of the antitumor action of interferon alpha. IFN alpha treatment induces hematologic and cytogenetic remissions in patients with chronic phase CML. In addition, the duration of the chronic phase is prolonged by IFN alpha resulting in a significant survival benefit. In two randomized clinical trials this survival benefit was demonstrated in all chronic phase CML patients independent of their risk scores. Moreover, IFN treatment also delays the onset of clinical relapse after allogeneic bone marrow transplantation. The critical mechanisms of IFN action have not yet been identified. Both direct and indirect antiproliferative mechanisms have been described. In particular, differential regulation of growth promoting and growth inhibiting cytokines represents an attractive hypothetical mechanism of IFN action. Nevertheless, no leukemia specific IFN activities explaining cytogenetic remissions and/or delay of disease progression have been identified. Further research on that field are required to further improve biological CML therapies.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Annals of hematology 71 (1995), S. 57-63 
    ISSN: 1432-0584
    Keywords: Key words CLL ; Hairy cell leukemia ; Low-grade lymphoma ; Cytokines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Chronic B-cell malignancies are characterized by accumulation of transformed B cells of low proliferative index in lymphatic and extralymphatic tissues. Cytokines do not appear to play a role in the primary step of transformation. However, proliferation as well as inhibition of apoptosis of malignant B cells can readily be explained by cytokine effects. Clinical trials of interferons (IFN) and interleukin-2 alone or in combination have been performed in patients with hairy cell leukemia (HCL), CLL, and low- and intermediate-grade non-Hodgkin’s lymphoma. While IFN alpha became standard therapy of HCL, responses in other entities were variable, ranging from 0 to 70% in selected populations. Combination of IFN and cyto-toxic chemotherapy in general revealed no additional benefit as compared to chemotherapy alone. Perspectives for future clinical testing of cytokines in low-grade B-cell lymphomas are discussed.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0584
    Keywords: Natural killing ; Hairy cell leukemia ; Interferon
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The number of large granular lymphocytes (LGL) and the capacity of peripheral blood mononuclear cells (PBMC) to lyse K 562 target cells in a natural killer (NK)-like fashion was evaluated in seven hairy cell leukemia (HCL) patients undergoing treatment with recombinant interferon-alpha-2 (rIFN-alpha-2). In HCL patients, whose peripheral blood showed high numbers (≧15×103/μl) of leukemic cells the number of LGL and their capacity to lyse K 562 tumor target cells were very low prior to treatment but increased significantly (p〈0.05) following interferon (IFN) therapy. In patients with low numbers of hairy cells (HC) in their peripheral blood, both these parameters were higher and remained largely unaffected throughout IFN treatment. In vitro, HC proved to be completely insensitive to natural killing when tested against unstimulated and IFN-activated LGL from healthy donors. These results fail to support the concept of IFN-mediated enhancement of host antitumor actions, responsible for the favourable clinical results in HCL.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Annals of hematology 71 (1995), S. 57-63 
    ISSN: 1432-0584
    Keywords: CLL ; Hairy cell leukemia ; Low-grade lymphoma ; Cytokines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Chronic B-cell malignancies are characterized by accumulation of transformed B cells of low proliferative index in lymphatic and extralymphatic tissues. Cytokines do not appear to play a role in the primary step of transformation. However, proliferation as well as inhibition of apoptosis of malignant B cells can readily be explained by cytokine effects. Clinical trials of interferons (IFN) and interleukin-2 alone or in combination have been performed in patients with hairy cell leukemia (HCL), CLL, and low- and intermediate-grade non-Hodgkin's lymphoma. While IFN alpha became standard therapy of HCL, responses in other entities were variable, ranging from 0 to 70% in selected populations. Combination of IFN and cytotoxic chemotherapy in general revealed no additional benefit as compared to chemotherapy alone. Perspectives for future clinical testing of cytokines in low-grade B-cell lymphomas are discussed.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
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  • 5
    ISSN: 1432-0584
    Keywords: Key words CML ; Interferon alpha ; Cytogeneticresponse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In a prospective multicenter phase-II trial 80 patients with Philadelphia (Ph)-positive chronic myelogenous leukemia (CML) were treated with recombinant interferon (IFN)α-2c, administered subcutaneously at an absolute dose of 3.5 megaunits (MU)/day. Complete hematological remission was achieved in 29 (39%) and partial hematological remission in 26 (35%) of the 74 patients evaluable for response. Major cytogenetic responses were observed in ten (13%) and minor cytogenetic responses in 11 patients (15%). Median duration of cytogenetic response was 33 months (range, 2–90); relapses were seen in all of the 11 patients with minor and in three of the ten patients with major cytogenetic responses. Median survival estimates for pretreated (n=19) and untreated (n=58) patients were 51 months (95% confidence interval [CI], 30–72) and 77 months (95% CI, 43–111), and the survival probabilities at 5 years were 45% and 54% for the two groups, respectively. Hematological response after 3 months of treatment demonstrated a clear-cut discriminative capacity with 5-year survival probabilities of 100%, 67% and 24% for patients achieving CHR (n=6), PHR (n=34), and less than PHR (n=35), respectively. Landmark analysis at 12, 18, and 24 months after start of IFN therapy and an analysis treating time to cytogenetic response as a time-dependent covariate showed that cytogenetic response was associated with longer survival. The impact of a low-dose IFN regimen on survival in CML patients is unclear and requires further clarification by randomized clinical trials. Early hematological and cytogenetic response to IFN-α treatment identifies patients with a favorable long-term prognosis.
    Type of Medium: Electronic Resource
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