Clinical study of Philadelphia chromosome-positive acute lymphoblastic leukemia

目的研究Ph染色体阳性(Ph+)急性淋巴细胞白血病(ALL)的生物学特点与临床治疗转归.方法30例成人ALL经MIC检查确诊为Ph+B细胞ALL.经环磷酰胺、长春新碱、柔红霉素、泼尼松加或不加左旋门冬酰胺酶(CODP±L)方案诱导化疗,化疗不缓解者给予伊马替尼治疗,400～600 mg/d,持续服用至完全缓解(CR).14例缓解后行异基因造血干细胞移植(allo-HSCT),16例进行巩固强化治疗.结果30例Ph+ALL患者占同期92例ALL患者的32.6%.中位年龄25.5(14～60)岁.单纯t(9;22)16例,有附加染色体异常14例;P190蛋白阳性率为68.4%;P210蛋白阳性率为31.6%;细胞免疫学标记均为B细胞表达,其中CD34细胞阳性率76.7%,髓系表达(CD13或CD33)阳性率43.3%.30例患者中WBC＞30×109/L 22例,其中9例WBC＞100×109/L.经常规化疗,单纯Ph+ALL缓解率为68.8%,伴附加染色体异常者为28.6%(P＞0.05);7例未缓解患者应用伊马替尼治疗均达CR,Ph+ALL总缓解率为73.3%.单纯Ph+ALL与伴附加染色体异常者的中位缓解期分别为9及4个月(P＜0.05);中位生存期分别为9个月及7个月(P＞0.05).移植患者与持续化疗者中位缓解期分别为8个月及4.5个月(P＜0.05);中位生存期为12.5及6个月(P＜0.05).结论有附加染色体异常对Ph+ALL患者的预后和疗效有一定的负性影响,伊马替尼对Ph+ALL诱导治疗有效,可为其提供移植机会,行allo-HSCT患者的生存期明显长于单纯化疗患者.To study the clinical characteristics and therapeutic outcome of Ph+ acute lymphoblastic leukemia (ALL).Thirty previously untreated cases of Ph+ B-ALL were diagnosed in our institute. The patients were treated with combination chemotherapy of CODP +/- L regimen, Imatinib (400 approximately 600 mg/d) was continuously given to those who couldn't reach CR. Fourteen patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT) after CR, while 16 received consolidation of intensive chemotherapy.Thirty (32.6%) of 92 ALL patients were diagnosed as Ph+ ALL, with a median age of 25.5 (14 - 60). Among them Ph+ as the sole anomaly was seen in 16 patients, and Ph+ with additional chromosome abnormalities in 14. Besides the B cell markers, 23 (76.7%) patients had CD34+ and 13 (43.3%) CD13+ and/or CD33+. Nineteen of the Ph+ ALL patients underwent molecular analysis; 13 (68.4%) expressed P190 and 6 (31.6%) P210. Increased WBC (> 30 x 10(9)/L) was found in 22/30 cases while WBC > 100 x 10(9)/L in 9/30 cases. The chemotherapy complete remission rate was 68.8% in patients with only Ph+ versus 28.6% in those with additional chromosome abnormalities. All seven refractory/relapsed patients reached CR with Imatinib therapy. The total complete remission rate was 73.3% in all Ph+ ALL patients. The median remission duration was shorter in patients with additional chromosome than in those with only Ph+ (1 vs 7 months, P < 0.05), and so was the survival period (7 vs 9 months, P > 0.05). The remission duration was significantly longer in patients received allo-HSCT than in those received chemotherapy only (8 vs 0.5 month, P < 0.05), and so was the survival period (12.5 vs 6 months, P < 0.05).Additional chromosome abnormalities negatively affect the prognosis and therapeutic effect of Ph+ ALL patients. Imatinib is effective for the induction therapy of Ph+ ALL. The survival period of patients who received allo-HSCT was obviously longer than those who received chemotherapy only.PubMed中文核心期刊要目总览(PKU)中国科学引文数据库(CSCD)0131-342