The effect of homoharringtonine in patients with chronic myeloid leukemia who have failed or responded suboptimally to imatinib therapy

Imatinib is the current standard first-line therapy for patients with newly diagnosed chronic myeloid leukemia (CML),but some of the patients will eventually develop resistance to imatinib therapy [1,2]; therefore, there is a subset of patients with CML for whom new therapeutic strategies are needed. It has been shown that homoharringtonine (HHT) has a synergistic or additive effect with imatinib in vitro against imatinib-resistant cell lines and cells from patients with CML in blastic phase [3‐ 5], so recently HHT has drawn more and more attention as one of the salvage therapy for patients resistant to imatinib. Here, we investigate the safety and efficacy of HHT combining with imatinib in patients with CML who failed or suboptimally responded to imatinib treatment. Patients with Phpositive CML treated with imatinib at a minimum dose of 400 mg per day for at least 3 months were eligible for the current study. Other eligibility criteria included the following [6,7]: (1) treatment failure: no hematologic remission (stable disease or disease progression), 3 months or less than complete hematologic remission (CHR), 6 months or less than partial cytogenetic response (PCyR), 12 months after imatinib treatment; (2) suboptimal response: less than CHR, 3 months or less than PCyR, 6 months or less than complete cytogenetic response (CCyR), 12 months after imatinib treatment. HHT, which is a racemic mixture of natural harringtonine and supplied by Hangzhou, China, was administered at a dose of 1.5 mg/m 2 daily by infusion at least 6 h for 7‐11 days every month. The precise days of HHT therapy for every course were adjusted according to the dose-limiting toxicity (DLT) in previous course. DLT was defined as any Grade � 3 nonhematologic adverse event occurring during the treatment. A hematologic DLT was defined as an neutrophil count 51610 9 /L or platelet count 550610 9 /L