成人Ph阴性急性淋巴细胞白血病的优化治疗

Optimal treatment of adult Ph negative acute lymphoblastic leukemia

目的 比较传统成人Ph阴性急性淋巴细胞白血病（ALL）治疗方案和借鉴儿童ALL的新化疗方案在疗效及安全性上的差异,并进一步分析这两种化疗方案对不同年龄段患者疗效的差异.方法 收集2009年1月4日至2013年9月4日收治的144例初治Ph阴性ALL患者资料,根据治疗方案分为传统的成人方案（方案1）组和借鉴儿童ALL的新化疗方案（方案2）组,分析其整体及不同分组条件下的疗效及安全性.结果 144例患者接受化疗后,总完全缓解（CR）率为95.8％,1个疗程CR率为92.4％,5年总生存（OS）率为59.0％,5年无复发生存（RFS）率为48.6％.其中方案1组和方案2组患者的CR率（95.6％和96.1％,P=0.783）、3年OS率（65.3％和63.4％,P=0.885）和3年RFS率（56.0％和50.0％,P=0.931）差异均无统计学意义.方案1组中,14～30岁患者的OS明显优于31～60岁患者（3年OS率69.6％对54.7％,P=0.042）,RFS差异则无统计学意义（3年RFS率56.5％对57.0％,P=0.472）;方案2组中,14～30岁患者与31～60岁患者在OS及RFS上差异均无统计学意义（3年OS率65.7％对60.3％,P=0.423;3年RFS率51.5％对46.6％,P=0.655）.两组患者在呼吸衰竭、心功能不全、真菌感染及肠梗阻发生率上差异均无统计学意义,方案1组患者的肾功能不全发生率低于方案2组（P=0.011）,菌血症发生率高于方案2组（P=0.000）.结论 Ph阴性ALL患者对两套化疗方案耐受性均较好,具有较高的CR率及长期生存率;同时,高龄（31～60岁）患者有可能从非骨髓抑制药物含量高、化疗强度低的方案2中受益.

Objective To analyze the difference of safety and efficacy between the traditional and the pediatric inspired acute lymphoblastic leukemia （ALL） chemotherapy regimen, and to fiarther observe whether patients in different age group will benefit from the two regimens. Methods Adult de novo Ph negative ALL patients in our hospital from Jan 4, 2009 to Sep 4, 2013 were involved in this study and divided into 2 groups according to treatment regimens, the traditional regimen （regimen 1 ） and modified pediatric regimen （regimen 2 ） groups, respectively. The safety and the efficacy of all patients and different regimen groups were evaluated statistically. Results All 144 patients received the induction therapy. The total complete remission （CR） rate was 95.8%, one course CR rate was 92.4%, and 5 year overall survival （OS） and progression free survival （RFS） were 59.0% and 48.6% respectively. The CR rate, 3 year OS and 3 year RFS between the two different regimens were 95.6% vs 96.1% （P=-0.783）, 65.3% vs 63.4% （P= 0.885） and 56.0% vs 50.0% （P=-0.931）, respectively. Further analysis stratified with age was also performed. For the patients treated with regimen 1, the 3 year OS and RFS between the two different age groups （14-30 years and 31-60 years） was 69.6% vs 54.7% （P=0.042） and 56.5% vs 57.0% （P=-0.472）. For the patients treated with regimen 2, the 3 year OS and RFS between the two different age groups （14-30 years and 31-60 years） was 65.7% vs 60.3% （P=-0.423） and 51.5% vs 46.6% （P=0.655）. No differences were found on the respiratory failure, cardiac dysfunction, fungal infection and intestinal obstruction between the two treatment regimen groups. The incidence of renal dysfunction for regimen 1 was lower than that of regimen 2 （P=0.011）. The incidence of bacteremia for regimen 1 was higher than that of regimen 2 （P=0.000）. Conclusion The two treatment regimens for adult Ph negative ALL patients were well tolerated and showed relative favorable CR rate and long term survival rate. The older patients （31-60 years） tended to benefit from the regiment 2 which was less intensive and consisted of more agents with low suppression to bone marrow.