To provide an overview of these results, we performed a literature search and meta-analysis of 2,314 patients from fifty-six studies to assess the overall efficacy and safety of HAG regimen in AML and MDS patients. The majority of these studies are published in Chinese, limiting the availability of these articles to the global scientific community. G-CSF leads to an enrichment of S-phase leukemic blasts, thereby improving the efficacy of cytarabine, which is active in the S-phase.Ī significant number of clinical trials have been performed using the HAG regimen in China. HHT and cytarabine act in a synergistic manner to induce apoptosis of leukemic cells. Cytarabine acts at the S-phase of the cell cycle to induce apoptosis. HHT is a protein synthesis inhibitor that causes leukemic cells to arrest at the G1/G2 phase of the cell cycle and can induce dose-dependent apoptosis in many acute myeloid cell lines and primary myeloid leukemia cells. HHT is a plant alkaloid first isolated from Cephalotaxus in China and has been used successfully in the treatment of acute and chronic myeloid leukemia since the 1970s. However, the cardiac toxicity associated with aclarubicin limits to a certain extent the application of the CAG regimen, especially in elderly patients with cardiac disease.Ī new chemotherapy regimen with less cardiac toxicity was developed for the treatment of AML consisting of low-dose homoharringtonine (HHT) and cytarabine as well as G-CSF priming, abbreviated as HAG. The CAG regimen has been widely used in China and Japan for the past two decades and proven efficacious in the treatment of refractory and relapsed AML as well as high-risk myelodysplastic syndrome (MDS). In 1995, Yamada and colleagues first proposed a novel low-dose chemotherapy for the treatment of AML consisting of low-dose cytarabine and aclarubicin combined with granulocyte colony-stimulating factor (G-CSF) priming, referred to as CAG. Biological characteristics contributing to these unsatisfactory outcomes include poor performance status (PS), poor tolerance for therapy, the emergence of drug resistant malignant clones, an immunocompromised state and multiple organ dysfunction. Standard induction therapy usually includes an anthracycline such as daunorubicin (Dau), idarubicin (Ida), or the anthracenedione mitoxantrone and cytarabine (Ara-C), which has resulted in improved treatment outcomes and prognosis for younger adults (<60 years) with acute myeloid leukemia (AML) however, in individuals with high-risk AML, including elderly, relapsed, refractory, and secondary AML, outcomes from intensive chemotherapy remain suboptimal. Reports of ED and rates of myelosuppression were reduced as compared with intensive chemotherapy ( P = 0.000 and P = 0.000, respectively). HAG regimen was well tolerated, with early death (ED) in 2%, grade IV myelosurrpression in 52% and infection in 50%. No significant differences in CR rates were observed between patients treated with HAG and those treated with CAG (cytarabine, aclarubicin, G-CSF) regimens ( P = 0.073). When compared with non-HAG regimens for AML/MDS induction therapy, the CR rate of patients treated with HAG was significantly higher than in treated with intensive chemotherapy ( P = 0.000). There were no significant difference in CR rates between elderly AML patients (54%) and all AML patients ( P = 0.721). The CR rate of patients with newly diagnosed AML (62%) was significantly higher than in patients with relapsed/refractory AML (50% P = 0.001). The complete response (CR) rate of AML patients (53%) was significantly higher than that of MDS/transformed-AML patients (45% P = 0.007).
0 Comments
Leave a Reply. |