Alkylating agents

Melphalan is an orally bioavailable alkylating agent with myelosuppressive properties. The action of alkylating agents in MMM includes a direct, nonspecific myelosup-pression, and therefore they may potentially palliate symptoms associated with myeloproliferation.79 A clinical trial was recently reported in MMM using low doses of melphalan.80 Over a 7-year period, 104 patients with MMM were treated with 2.5 mg of oral melphalan three times a week. The agent was active, with 66% of patients achieving a response after a median of 7 months of therapy. The greatest impact was on myeloproliferative manifestations. However, the major reason for study discontinuation was blastic transformation in 26% of the study cohort, as high as 48% in pretreated patients. Thus, the long-term use of melphalan in MMM may increase the risk of LT and should be used only in appropriate circumstances (e.g., the older patient who needs myelosuppression and is not a candidate for/or has not responded to hydroxyurea).

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