Zhang Yue-feng, Chen Zhi-mei, Lou Ji-yu, Ni Wan-mao, Wang Yun-gui, Meng Hai-tao, Tong Hong-yan, Qian Wen-bin, Jin Jie
Department of Hematology, First Affiliated Hospital of Zhejiang University, College of Medicine, Hangzhou 310003, China.
Zhonghua Xue Ye Xue Za Zhi. 2011 Dec;32(12):814-8.
To study the clinical characteristics, risk factors and therapeutic outcome of Philadelphia chromosome-positive adult acute lymphoblastic leukemia (Ph(+)aALL).
The clinical data of 117 newly diagnosed adults with Ph(+)ALL in our hospital between January 1995 and December 2009 were retrospectively analyzed. And their prognoses were followed up.
There were 117(16.1%) of 727 aALL patients diagnosed as Ph(+)aALL. Among the 117 cases, 64.1% patients were classified as pre-B immunophenotype and 31.3% as common B immunophenotype, 37.5% patients with co-expression of myeloid antigens (CD13 or CD33), and 98.4% patients with positive CD34. The complete remission (CR) rate after 1 or 2 cycles of induction chemotherapy was 62.2% in Ph(+)aALL group versus 82% in Ph(-)aALL group (P = 0.000). The median disease-free survival time of Ph(+) group was 6 months and the median survival time was 9 months. Sole karyotype abnormality subgroup t(9;22) accounted for 53% of all Ph(+)aALL patients and additional karyotype abnormality subgroup, t(9;22) plus other chromosome variation, accounted for 47%. Patients in sole karyotype abnormality subgroup had slightly lower CR rate (59.6% vs 62.5%, P = 0.768), longer median survival time (7 months vs 4 months, P = 0.158), and higher 3-year overall survival rate (27.3% vs 14.4%, P = 0.271). For the myeloid antigen co-expressed patients and the only lymphocytic antigen expressed ones, CR rate was 56.0% and 61.5% (P = 0.750), the median survival time was 5 months and 4 months (P = 0.182), and the 3-year overall survival rate was 16.0% and 15.0% (P = 0.354), respectively. In the imatinib plus combination chemotherapy treatment group, 81.3% patients achieved CR, compared with that of 58.3% in patients treated with only traditional combination chemotherapy (P = 0.083). The median survival time was 9.5 months and 6 months (P = 0.003) in these two subgroup, and 3-year overall survival rate was 52.2% and 10.3% (P = 0.029), respectively. For the patients receiving allo-HSCT after CR and that receiving traditional consolidation chemotherapy, the median survival time was 15 months and 6 months (P = 0.000), and the 3-year overall survival rate was 62.0% and 10.3% (P = 0.000), respectively. For the patients receiving imatinib as consolidation-maintenance treatment and that receiving allo-HSCT, the median survival time was 12 months and 15 months (P = 0.300), and the 3-year overall survival rate was 64.7% and 62% (P = 0.505), respectively.
Of all adult ALL patients, the Ph(+) subgroup accounted for about 16.1%, which have unfavorable prognosis such as lower CR rate and shorter survival duration under traditional chemotherapy. Neither additional chromosome abnormalities to t(9;22) nor co-expression of myeloid antigen had negative effect on CR rate and survival duration. Addition of imatinib to the therapy was beneficial to improve the CR rate and survival duration. Either receiving imatinib as consolidation-maintenance treatment or allo-HSCT after complete remission can improve long-term survival rate of Ph(+) adult ALL group significantly.
研究费城染色体阳性成人急性淋巴细胞白血病（Ph(+)aALL）的临床特征、危险因素及治疗效果。
回顾性分析1995年1月至2009年12月我院117例新诊断的Ph(+)ALL成年患者的临床资料，并对其预后进行随访。
727例aALL患者中有117例（16.1%）被诊断为Ph(+)aALL。在这117例患者中，64.1%为前B免疫表型，31.3%为普通B免疫表型，37.5%患者髓系抗原（CD13或CD33）共表达，98.4%患者CD34阳性。Ph(+)aALL组诱导化疗1或2周期后的完全缓解（CR）率为62.2%，而Ph(-)aALL组为82%（P = 0.000）。Ph(+)组的无病生存期中位数为6个月，总生存期中位数为9个月。单纯核型异常亚组t(9;22)占所有Ph(+)aALL患者的53%，额外核型异常亚组，即t(9;22)加其他染色体变异，占47%。单纯核型异常亚组患者的CR率略低（59.6%对62.5%，P = 0.768），总生存期中位数较长（7个月对4个月，P = 0.158），3年总生存率较高（27.3%对14.4%，P = 0.271）。对于髓系抗原共表达患者和仅表达淋巴细胞抗原患者，CR率分别为56.0%和61.5%（P = 0.750），总生存期中位数分别为5个月和4个月（P = 0.182），3年总生存率分别为16.0%和15.0%（P = 0.354）。在伊马替尼联合化疗治疗组中，81.3%患者达到CR，而仅接受传统联合化疗患者的CR率为58.3%（P = 0.083）。这两个亚组的总生存期中位数分别为9.5个月和6个月（P = 0.003），3年总生存率分别为52.2%和10.3%（P = 0.029）。对于CR后接受异基因造血干细胞移植（allo-HSCT）的患者和接受传统巩固化疗的患者，总生存期中位数分别为15个月和6个月（P = 0.000），3年总生存率分别为62.0%和10.3%（P = 0.000）。对于接受伊马替尼作为巩固维持治疗的患者和接受allo-HSCT的患者，总生存期中位数分别为12个月和15个月（P = 0.300），3年总生存率分别为64.7%和62%（P = 0.505）。
在所有成年ALL患者中，Ph(+)亚组约占16.1%，在传统化疗下预后不佳，如CR率较低和生存期较短。t(9;22)额外的染色体异常或髓系抗原共表达对CR率和生存期均无负面影响。治疗中加入伊马替尼有利于提高CR率和生存期。完全缓解后接受伊马替尼作为巩固维持治疗或allo-HSCT均可显著提高Ph(+)成年ALL组的长期生存率。
