| Objective To observe the efficacy of a second-generation tyrosine kinase inhibitor(TKI)dasatinib in 16 patients with chronic myelogenous leukemia(CML)in advanced phase.Methods We choose 16 patients(pts) diagnoed with chronic myelogenous leukemia in advanced phase, which from February 2012 to November 2013 in the first affiliated hospital of Anhui Medical University and Anqing municipal hospital in hematology-confirmed inpatient or outpatient. All the pts, including 3 pts in AP and 13 pts in BP, received dasatinib 70 mg twice daily for 3 pts or 140 mg once daily for 4 pts or100 mg once daily for 8 pts or 50 mg twice daily for 1 patient. The clinical efficacy,hematologic/cytogenetic response and adverse effects(AE) of the pts were assessed.Results All the pts received dasatinib treatment. Among 13 blast-phase pts, 4 cases got lymphoid blast crisis, 5 cases got granulocytic blast crisis, and other 4 cases got monocytic blast crisis. 9 pts(56.25%) achieved complete hematologic remission(CHR),with a median remission duration of 3 months; 2 of 3 accelerated-phase pts and 7 of 13blast-phase pts achieved CHR; 4 patients with evolution to lymphoid blast crisis all achieved CHR, among whom 1 patient replased after 2-year remission, 1 patient evoluted to myeloid blast crisis after 18-month remission and died 2 months later, and 1patient died of umbilical cord blood transplantation; 3 of 5 pts with granulocytic blast crisis achieved CHR; no CHR was observed in 4 patients with CML monocytic blast crisis. No significant difference was found for the rate of CHR and complete cytogenetic response(CCy R) between the accelerated-phase and blast-phase groups(P=1.000). The rate of disease progression was increased in blast-phase group(P=0.136). Grade 3 or higher hematologic adverse events were also elevated for patients with blast-phase CML(P=0.518). 10 of 16 pts(62.5%) experienced grade 3-4 of hematologic AEs related to dasatinib but manageable by temporary drug withdrawal or supportive care. In the common non-hematologic AEs related to dasatinib, 3 of16pts(18.75%) experienced pleural effusion, 6 of 16 pts(37.5%) experienced fever, and4 of 16 pts(25%) experienced gastrointestinal reaction. All of the patients in the process of taking no liver function damage and QTc duration. 10 of 16 pts died, and the follow-up time of the rest ranged from 2 to 24 months. The 2-year survival rate was37.5%(6 cases/16 cases) and median overall survival was 12 months(95%CI: 0-24.9months).Conclusion Dasatinib is effective in pts with CML in advanced phase, with higher remission rate of hematology and genetics, which may be a priority option for pts in accelerated-phase and pts with evolution to lymphoid blast crisis and granulocytic blast crisis. However, for pts with evolution to monocytic blast crisis,dasatinib alone is not that effective; due to the heterogeneity of disease and the different remission duration of the disease, when disease recoveries to its chronic phase,allogeneic hematopoietic stem cell transplantation(Allo-HSCT) may be considered as early as possible, with hope to get higher progression-free-survival(PFS). Dasatinib can strive for time and opportunity for the patients who have the conditions to accept AlloHSCT. |
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