Interferon-a is a member of a family of glycoproteins that have antiviral and antiproliferative properties. It was first shown to be an active agent in CML in the early 1980s. Although interferon-a has significant activity in early chronic-phase patients, it has only modest activity in late chronic-phase CML and minimal activity in the accelerated or blastic phase. In several large, prospective, randomized trials, interferon-a increased survival when administered in the chronic phase, and a meta-analysis of several major trials showed a significant survival advantage for interferon-a over hydroxyurea and busulfan. In this meta-analysis, 5-year survival rates were 57 and 42% for interferon-a and chemotherapy, respectively. A complete hematological response (CHR) is seen in most (70%) patients treated with interferon-a. A cytogenetic response, defined as a decrease in the percentage of Philadelphia chromosome-positive metaphases in the marrow to less than 35%, is seen in 30-50% of patients, with complete cytogenetic responses in only 10-20% of interferon-treated patients. This group of patients with complete cytogenetic responses gains the greatest survival advantage and has a median survival of more than 8 years. Up to 20% of patients tolerate interferon-a poorly, necessitating discontinuation of treatment. These side effects include fevers, chills, arthralgias, myalgias, fatigue, depression, weight loss, peripheral neuropathy, myelosuppres-sion and hepatotoxicity.
Investigators have sought to improve on the success of treatment with interferon-a by adding cytosine arabinoside (also called cytarabine or Ara-C), another agent with antileukemic activity. One randomized trial of the combination showed significantly improved response rates over interferon-a alone, which translated into an overall survival advantage. A subsequent study found improved response rates but no survival advantage for the combination. In addition, the combination of interferon-a and cytarabine is associated with increased gastrointestinal and marrow toxicity and, not surprisingly, many patients tolerate it poorly. Another potential problem with the use of interferon-a is that it may compromise the outcome of subsequent transplantation owing to an increase in graft rejection or graft-versus-host disease (GVHD). However, there are conflicting data on this issue and many recommend discontinuing interferon-a at least 3 months before transplantation.
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