费城染色体阳性成年急性淋巴细胞白血病患者治疗效果及预后因素分析

目的 分析费城染色体阳性(Ph+)的成年急性淋巴细胞白血病(ALL)患者治疗效果及预后影响因素.方法 回顾性分析49例Ph+ALL患者的临床资料,探讨治疗效果及不同因素对预后的影响.结果49例患者中,男性24例,女性25例;中位年龄38岁(15~77岁),酪氨酸激酶抑制剂(TKI)治疗组血液学完全缓解(CR)率、主要分子生物学反应(MMR)率及完全分子生物学缓解(CMR)率均高于单纯化疗组(96.8 %比72.2 %,64.5 %比16.7 %,25.8 %比11.1 %),差异均有统计学意义(χ2=4.308,P=0.038;χ2=10.468,P=0.001;χ2=4.250,P=0.039).生存分析提示中位总生存(OS)时间为24个月(3~70个月),3年OS率及无复发生存(RFS)率分别为32.7 %、21.4 %;TKI治疗组3年OS率及1年RFS率高于单纯化疗组(40.3 %比11.1 %,67.8 %比11.1 %),差异有统计学意义(χ2=12.725, P<0.001;χ2=17.401,P<0.001);异基因造血干细胞移植(allo-HSCT)组3年OS率及RFS率高于非移植组(62.5 %比25.7 %、41.7 %比15.0 %),差异有统计学意义(χ2=6.196,P=0.013;χ2=8.032,P=0.005);经2个疗程治疗后达MMR组3年OS率及RFS率分别为45.1 %和28.9 %,高于未达MMR组(17.6 %和11.7 %),差异有统计学意义(χ2=5.446,P=0.020;χ2=6.484,P=0.011);Cox多因素分析结果显示,联合TKI治疗(HR=0.227,95 % CI 0.094~0.550,P=0.001)是OS的独立预后因素;联合TKI治疗(HR=0.225,95 % CI 0.082~0.618,P=0.004)及移植(HR=0.275,95 % CI 0.077~0.983,P=0.047)是RFS的独立预后因素.结论 联合TKI治疗能提高患者CR、MMR及CMR率,提高长期生存,为患者接受移植提供更多机会;在TKI时代,移植仍是治疗Ph+ALL的重要方法,尤其那些经化疗联合TKI治疗但早期未达MMR者预后差,应尽早行造血干细胞移植.

Therapeutic effect and prognostic factors of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia

Objective To explore the outcome and prognostic factors of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL). Methods Forty-nine newly diagnosed adult patients with Ph+ALL were analyzed retrospectively, and the treatment effect and the impact of different factors on prognosis were explored. Results In 49 patients, there were 24 males and 25 females;the median age was 38 years (range 15-77 years). Hematologic complete remission (CR), major molecular response (MMR) and complete molecular remission (CMR) rate in patients received tyrosine kinase inhibitors (TKI) plus chemotherapy were higher than those in patients received chemotherapy only (96.8 % vs. 72.2 %, χ2= 4.308, P= 0.038; 64.5% vs. 16.7 %, χ2=10.468, P= 0.001; 25.8 % vs. 11.1 %, χ2=4.250, P=0.039). With a median overall survival (OS) of 24 months (3-70 months), the 3-year OS and relapse-free survival (RFS) rates were 32.7 % and 21.4 %, respectively. The 3-year OS rate and 1-year RFS rate in TKI plus chemotherapy group were 40.3 % and 67.8 % respectively, which were higher than those in chemotherapy group (11.1 % and 11.1 %) (χ2= 12.725, χ2= 17.401, both P< 0.001). The 3-year OS and RFS rates in the allogeneic hematopoietic stem cell transplantation (allo-HSCT) group were higher than those in the group without allo-HSCT(62.5 % vs.25.7 %,χ2= 6.196,P= 0.013; 41.7 % vs. 15.0 %,χ 2= 8.032, P=0.005).The 3-year OS and RFS rates in patients achieved MMR after 2 circles treatment were higher than those in the others (45.1 % vs. 17.6 %,χ2= 5.446,P= 0.020; 28.9 % vs. 11.7 %,χ 2= 6.484,P= 0.011). Multivariate analysis showed that received TKI (HR= 0.227, 95 % CI 0.094-0.550, P= 0.001) was an independent prognostic factor for OS; received TKI (HR= 0.225, 95 % CI 0.082-0.618, P= 0.004) and allo-HSCT (HR=0.275, 95 % CI 0.077-0.983, P=0.047) were independent prognostic factors for RFS. Conclusions TKI can increase CR,MMR and CMR rates,improve outcome,and give more chance to receive HSCT.In TKI era,allo-HSCT is still the important treatment for Ph+ALL,especially for patients without MMR.