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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
    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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