伊马替尼治疗124例慢性粒细胞白血病加速期和急变期疗效追踪

目的评价甲磺酸伊马替尼（伊马替尼）治疗Ph阳性（Ph^＋）慢性粒细胞白血病（CML）加速期和急变期的疗效。方法对75例Ph^＋CML加速期患者和49例急变期患者持续口服伊马替尼400mg／d或600mg／d进行疗效观察。结果加速期：中位追踪23．0（1．0～64．0）个月，累积获得的血液学总有效率为93．3％，包括完全血液学缓解（CHR）85．3％和回到慢性期（RCP）8．0％，无效6．7％。累积获得的主要细胞遗传学缓解（MCyR）率为33．0％，其中完全细胞遗传学缓解（CCyR）率为28．0％，获得CCyR患者中主要分子学缓解（MMoR）率为47．6％。治疗有效者中，预计4年无疾病进展生存（PFS）率和总生存（OS）率分别为48．2％和52．2％。全部患者中，严重白细胞、血红蛋白和血小板减少的发生率分别为37．3％、34．6％和45．3％。急变期：中位追踪4．5（0．3～63．0）个月，累积获得的血液学总有效率为63．3％，包括CHR44．9％和RCP18．4％，无效36．7％。累积获得的MCyR率和CCyR率均为12．2％，其中MMoR率为33．3％。治疗有效者中，预计1年PFS率和OS率分别为32．8％和46．0％，2年PFS率和OS率分别为15．8％和21．0％。全部患者中，严重白细胞、血红蛋白和血小板减少的发生率分别为75．5％、71．4％和73．5％。结论①伊马替尼对Ph^＋CML的疗效随疾病进展的程度递减，严重血液学毒性递增。②多数加速期患者PFS期明显延长，特别是获得持久CCyR甚至MMoR者。③绝大部分急变期患者血液学效应短暂，复发率高。

The efficacy of imatinib mesylate for 124 patients with chronic myeloid leukemia in accelerated and blastic phase

OBJECTIVES: To evaluate the efficacy and safety of imatinib mesylate (imatinib) for patients with Philadelphia chromosome-positive (Ph+ ) chronic myeloid leukemia (CML) in accelerated and blastic phase. METHODS: Seventy-five Ph+ CML patients in accelerated phase and 49 in blastic phase were treated with 400 mg or 600 mg of imatinib once daily. RESULTS: For patients in accelerated phase, the cumulative hematological response (HR) rate was 93.3%, including complete HR (CHR) rate 85.3%, and returning to chronic phase (RCP) rate 8% in a median follow-up of 23.0 (1.0 -64.0 ) months. Cumulative major cytogenetic response (MCyR) rate was 33.0%, and complete cytogenetic response (CCyR) rate 28.0%. For patients with CCyR, the major molecular response (MMoR) rate was 47.6%. The estimated 4-year progression-free survival (PFS) rate and overall survival (OS) rate were 48.2% and 52.2% in patients with HR, respectively. Severe leukocytopenia, anemia and thrombocytopenia occurred in 37.3%, 34.6% and 45.3% of all patients, respectively. For patients in blastic phase, the cumulative HR rate was 63.3%, including CHR rate 44.9%, and RCP rate 18.4% in a median follow-up of 4.5 (0.3 -63.0) months. Cumulative MCyR rate and CCyR rate were both 12.2%. For patients with CCyR, the MMoR rate was 33.3%. For patients with HR, the estimated 1-year/2-year PFS and OS rates were 32.8%/15.8% and 46.0%/ 21.0% respectively. Severe leukocytopenia, anemia and thrombocytopenia occurred in 75.5%, 71.4% and 73.5% of all patients, respectively. CONCLUSIONS: The efficiency of imatinib was decreasing, and severer hematological toxicities increasing with the disease progressing in patients with Ph+ CML. Imatinib improves progression-free survival significantly in most patients in accelerated phase, particularly in those with continuous CCyR or MMoR. The response duration in majority of blastic phase patients is short, and the relapse rate is high.