title: Homoharringtonine therapy induces responses in patients with chronic myelogenous leukemia in late chronic phase.
abstract: Homoharringtonine (HHT) is a plant alkaloid with potent myelosuppressive activity and little toxicity when used in a continuous infusion schedule. The antileukemic efficacy of HHT has been shown in acute myeloid leukemia, but has not been investigated in chronic myelogenous leukemia (CML). Seventy-one patients with Philadelphia chromosome-positive (Ph+) CML in late chronic phase (time from diagnosis to therapy longer than 12 months) were treated with a continuous infusion of HHT at a daily dose of 2.5 mg/m2 for 14 days for remission induction and for 7 days every month for maintenance. The median number of courses given was 6 (range, 1 to 35) and 21 patients (30%) continue on treatment. Forty-two of 58 patients (72%) evaluable for hematologic response achieved a complete hematologic remission, and 9 (16%) had a partial hematologic remission. Twenty-two of 71 patients (31%) developed a cytogenetic response; it was major (Ph+ cells less than 35%) in 11 (15%) and complete (Ph+ cells 0%) in 5 (7%). Significant myelosuppression occurred in 39% of induction courses and 9% of maintenance courses. Fever or documented infection was present in 26% of induction courses and in only 8% of maintenance courses. Nonmyelosuppressive toxicity was minimal. Homoharringtonine produced hematologic remissions in the majority of patients with advanced chronic-phase CML. Cytogenetic response occurred in some patients without an association with myelosuppression, and these responses may be prolonged. Future studies investigating homoharringtonine in combination with other active agents in CML, such as interferon, are warranted.
authors.affiliation: Department of Hematology, University of Texas MD Anderson Cancer Center, Houston 77030, USA.
authors.forename: S
authors.initials: S
authors.lastname: O'Brien
authors.forename: H
authors.initials: H
authors.lastname: Kantarjian
authors.forename: M
authors.initials: M
authors.lastname: Keating
authors.forename: M
authors.initials: M
authors.lastname: Beran
authors.forename: C
authors.initials: C
authors.lastname: Koller
authors.forename: L E
authors.initials: LE
authors.lastname: Robertson
authors.forename: J
authors.initials: J
authors.lastname: Hester
authors.forename: M B
authors.initials: MB
authors.lastname: Rios
authors.forename: M
authors.initials: M
authors.lastname: Andreeff
authors.forename: M
authors.initials: M
authors.lastname: Talpaz
mesh_terms: D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D003967:Diarrhea / Q000139:chemically induced; D005260:Female; D006248:Harringtonines / Q000627:therapeutic use*; D000077863:Homoharringtonine; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D007239:Infections; D016898:Interferon-alpha / Q000627:therapeutic use; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D015466:Leukemia, Myeloid, Chronic-Phase / Q000188:drug therapy* / Q000401:mortality / Q000628:therapy; D007970:Leukopenia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D015996:Survival Rate; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D006248:Harringtonines; D007155:Immunologic Factors; D016898:Interferon-alpha; D000077863:Homoharringtonine