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Chronic Myelogenous Leukemia Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Chronic-Phase Chronic Myelogenous Leukemia

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With the advent of imatinib, dasatinib, and nilotinib, the timing and sequence of allogeneic BMT or SCT has been cast in doubt.[24] Allogeneic SCT is the preferred choice for patients presenting with accelerated-phase or blast-phase disease, for patients with a T3151 mutation (resistant to currently available tyrosine kinase inhibitors), and for patients with complete intolerance to the pharmacologic options.[40]

In a prospective trial of 354 patients aged younger than 60 years, 123 of 135 patients with a matched, related donor underwent early allogeneic SCT while the others received interferon-based therapy and imatinib at relapse; some also underwent a matched, unrelated-donor transplant in remission.[41] With a 9-year median follow-up, survival still favored the drug treatment arm (P = .049), but most of the benefit was early as a result of transplant-related mortality, with the survival curves converging by 8 years.[41][Level of evidence: 2A] Among the many unanswered questions are the following:

  • Should younger eligible patients move quickly toward allogeneic SCT after induction failure by imatinib mesylate?
  • Does the substantial toxicity and mortality of allogeneic transplantation render its early use obsolete?

Clinical trials and long-term results from ongoing trials will be required before these controversies are resolved.

Biologic therapy with or without chemotherapy

Long-term data are available for initial treatment with interferon alpha. A meta-analysis of seven trials that randomly assigned patients to receive interferon or conventional chemotherapy (hydroxyurea or busulfan) demonstrated a 30% reduction in the annual death rate for patients who received interferon (P < .001).[42][Level of evidence: 1iiA] The annual death rate was reduced by 26% in the trials of interferon versus hydroxyurea (P = .001) and 36% in the trials of interferon versus busulfan (P = .007). Median survival was prolonged by 1 to 2 years; 5-year survival rate was 57% for patients treated with interferon and 42% for patients treated with chemotherapy (P < .001). Further analysis of the two trials, which included a three-way randomization between interferon, hydroxyurea, and busulfan, showed hydroxyurea to be superior to busulfan, decreasing the proportional odds of death by 24% (P = .02).[42] About 20% of the chronic-phase patients treated with interferon alpha have complete cytogenetic remissions with temporary disappearance of Philadelphia chromosome (Ph1)-positive cells in the marrow, and in about 10% of the patients these cytogenetic responses are quite long lasting.[43,44,45] These data have only been published in the context of a review article, rather than a peer-reviewed research manuscript.[45]

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