87例成人Ph染色体阴性ALL预后影响因素分析

Analysis of Factors Influencing Prognosis of 87 Adults with Ph Chromosome Negative ALL

目的:探讨影响成人费城(Ph)染色体阴性急性淋巴细胞白血病(ALL)患者总完全缓解(CR)、复发、无病生存(DFS)和总生存(OS)率的因素及后续异基因造血干细胞移植(allo-HSCT)对预后的影响。方法:收集本院收治的87例成人Ph阴性ALL患者的临床资料进行回顾性分析,诱导化疗方案为CHOP、左旋门冬酰胺酶(L-Asp),巩固化疗方案为CHOP+改良Hyper-CVAD或甲氨蝶呤治疗。巩固化疗3-6个疗程后,45例(51.72%)患者采用allo-HSCT治疗,42例(48.28%)患者继续维持巩固化疗。存活患者平均随访时间为40.13(3-60)个月。结果:87例患者中,早期死亡1例(1.15%)。86例可评估患者中,1个疗程结束达CR者为68例(79.07%),总CR达80例(93.02%)。多因素回归分析结果发现,肝脾/淋巴结肿大、白细胞计数≥100×109/L是患者总CR的影响因素(均P<0.05)。80例CR患者中,复发27例(33.75%);5年OS为47.50%,DFS为45.00%。多因素回归分析结果还发现,诱导化疗未应用L-Asp、诊断时合并中枢神经系统白血病、未行allo-HSCT、诱导化疗4周后未达CR是患者复发、生存预后不良的影响因素(均P<0.05)。以是否合并中枢神经系统白血病、诊断时白细胞计数是否高于100×109/L、是否行L-Asp诱导化疗、诱导化疗4周后是否达CR等4个预后因素对患者进行分组:无不良预后因素为低危组,伴有1个不良预后因素为中危组,伴有2-4个不良预后因素为高危组。统计结果发现,低危组是否行alloHSCT治疗对OS、DFS并无明显影响(均P>0.05);中、高危组行allo-HSCT治疗的患者OS、DFS较无alloHSCT治疗者明显升高(均P<0.05)。结论:合并中枢神经系统白血病、白细胞计数偏高(≥100×109/L)、未行LAsp诱导化疗、化疗4周后未达CR、后续未行allo-HSCT治疗均是成人Ph阴性ALL患者的影响因素,对伴有上述不良预后因素的患者应积极采取allo-HSCT治疗。

Objective： To explore the factors influencing total complete remission（ CR）,recurrence,disease-free survival（ DFS） rate and overall survival（ OS） rate in adults with Philadelphia（ Ph） chromosome negative acute lymphoblastic leukemia（ ALL） and the effect of subsequent allogeneic hematopoietic stem cell transplantation（ alloHSCT） on prognosis. Methods： The clinical data of 87 adult patients with Ph negative ALL were retrospectively analyzed,the CHOP regimen plus L-asparaginase（ L-Asp） was used for the induction therapy,and the CHOP ＋modified Hyper-CVAD or methotrexate was set up as the consolidation chemotherapy regimen. After consolidation chemotherapy for 3-6 courses,45 patients（ 51. 72%） received allo-HSCT,and 42 patients（ 48. 28%） continually received the maintained consolidation chemotherapy. The average follow-up time of the surviving patients was 40. 13（ 3-60 months）. Results： Out of 87 patients with Ph-ALL one patient died（ 1. 15%）. In 86 patients who could be evaluated,68 cases（ 79. 67%） reached CR at the end of 1 course,80 cases obtained CR（ 93. 02%）. Multivariate regression analysis showed that the enlargement of lever,spleen and lymphomode,WBC count≥ 100 × 10^9/L were affecting factors for total CR（ P〈0. 05）. Among 80 cases with CR,27 cases（ 33. 75%） relapsed,5 years＇ overall survival（ OS） rate and disease-free survival（ DFS） rate were 47. 50% and 45. 00% respectively. Multivariate regression analysis yet showed that the induction chemotherapy without L-Asp,presence of CNS leukemia at diagnosis,absence of allo-HSCT and no CR after indution chemotherapy for 4 weeks were affecting factors for relapse and poorprognosis of patients（ P〈0. 05）. According to 4 prognostic factors such as presence of CNS leukemia or no,WBC count ≥ 100 × 10^9/L or no,induction chemotherapy with L-Asp or no and CR after induction chemotherapy for 4 weeks or no,86 patients were divided into low-risk group（ without poor prognostic factor）,middle-risk group（ with 1 poor prognostic factor）,high-risk group（ with 2-4 poor prognostic factors）. Statistical results showed that allo-HSCT treatment in low-risk group had no significant effect on OS and DFS（ P〈0. 05）. The rate of OS and DFS in middle and high-risk group were significantly higher than those of patients without allo-HSCT treatment（ P〈0. 05）. Conclusion：Patients with central nervous system leukemia,high white blood cell count（ ≥100 × 10^9/L）,induction chemotherapy without L-Asp,no CR after 4 weeks of chemotherapy and absence of allo-HSCT treatment are the factors influencing the prognosis of adult patients with Ph negative ALL,so the patients with those poor prognostic factors should take active treatment of allo-HSCT.