BFM-90、CHOP和CHOP/HD-MTX方案治疗儿童青少年B细胞非霍奇金淋巴瘤的生存率比较

Comparing CHOP, CHOP+HD-MTX,and BFM-90 Regimens in the Survival Rate of Children and Adolescents with B Cell Non Hodgkin's Lymphoma

背景与目的儿童青少年B细胞非霍奇金淋巴瘤(Bcellnon-Hodgkinslymphoma,B-NHL)恶性程度高、进展快、早期患者对常规CHOP方案化疗可获得较好疗效,但晚期患者疗效差。对不同分期的患者应如何治疗值得进一步探索。本文回顾性分析和比较CHOP、CHOP+HD-MTX和德国BFM-90方案治疗儿童青少年B-NHL的疗效、不良反应和生存率。方法CHOP方案组30例3～17岁初治的B-NHL患者,Ⅰ/Ⅱ期13例,Ⅲ/Ⅳ期(StJude分期)17例,均接受2～8疗程常规CHOP方案化疗,每3周重复。CHOP+HD-MTX组18例3～14岁初治的B-NHL患者,Ⅰ/Ⅱ期6例,Ⅲ/Ⅳ期(StJude分期)12例,均接受2～8疗程CHOP+HD-MTX方案化疗和鞘注,每4周重复。BFM-90方案组25例1.5～15岁的初治的B-NHL患者,Ⅱ期7例,Ⅲ/Ⅳ期(StJude分期)18例,均接受NHL-BFM-90方案化疗。Ⅰ/Ⅱ期患者接受A和B疗程交替化疗共4～6疗程;Ⅲ/Ⅳ期患者接受AA和BB疗程交替化疗共6疗程,每疗程间隔18～21天。结果CHOP组21例(70%)完全缓解(completeresponse,CR),4例(13%)部分缓解(partialresponse,PR);有20%的疗程发生Ⅲ/Ⅳ级血液毒性。CHOP+HD-MTX组15例(83%)CR,3例(16%)PR;有52%疗程发生Ⅲ/Ⅳ级血液毒性。BFM-90方案组24例(96%)CR,1例(4%)PR;Ⅲ/Ⅳ级血液毒性A疗程57%,B疗程60%,AA疗程91%,BB疗程76%;

BACKGROUD &OBJECTIVES: B cell non Hodgkins lymphoma (B NHL) in childhood and adolescence is aggressive. Routine CHOP regimen can improve the survival rate of patients with early stage disease, but its effect on patients with advanced disease was poor. Therefore, it is worthwhile to further investigate how to treat patients with B NHL at different stages. This study was designed to retrospectively analyze and compare CHOP, CHOP+HD MTX, and BFM 90 regimens in the survival rate of children and adolescents with B NHL,and explore the optimal therapeutic strategy and protocols. METHODS: Thirty cases of 3 to 17 year old untreated patients with B NHL were enrolled in CHOP group, with 13 in Stage Ⅰ/Ⅱ, and 17 in stage Ⅲ/Ⅳ(St Jude staging), all patients received standard CHOP for 2 to 8 cycles, the regimen was repeated every 3 weeks. Eighteen cases of 3 to 14 year old untreated patients with B NHL were enrolled in CHOP+HD MTX group, with 6 in Stage Ⅰ/Ⅱ, and 12 in stage Ⅲ/Ⅳ(St Jude staging), all patients received CHOP+HD MTX and intrathecal injection for 2 to 8 cycles, the regimen was repeated every 4 weeks. Twenty five cases of 1.5 to 15 year old untreated patients with B NHL were enrolled in BFM 90 group, with 7 in Stage Ⅰ/Ⅱ,and 18 in stage Ⅲ/Ⅳ(St Jude staging). The patients with stage Ⅰ/Ⅱdisease received A schema alteration with B schema of BFM 90 regimen for 4 to 6 cycles, while the patients with stage Ⅲ/Ⅳdisease received AA schema alteration with BB schema of BFM 90 regimen for 6 cycles, the interval of cycles was 18 21 days. The survival rates were evaluated by Kaplan Meier method. RESULTS: In CHOP group,complete response (CR)rate was 70%(21/30),and partial response (PR) rate was 13%(4/30). In CHOP+HD MTX group, CR rate was 83%,PR rate was 16%. In BFM 90 group, CR rate was 96%(24/25),and PR rate was 4%(1/25). The hematologic toxicity incidence was higher in BFM 90 group than in the other 2 groups. In CHOP group, the overall 2 year survival rate was 52.79%(72.73%for Stage Ⅰ/Ⅱ, and 37.82%for stage Ⅲ/Ⅳ). In CHOP+HD MTX group, the overall 2 year survival rate was 55.56 %(83.33 %for Stage Ⅰ/Ⅱ, and 41.67 %for stage Ⅲ/Ⅳ). There was no significant difference between CHOP group and CHOP+HD MTX group in survival rate (P=0.78). In BFM 90 group,2 year event free survival rate (EFS) was 84.01 %(100%for StageⅠ/Ⅱ, and 77.04 %for stage Ⅲ/Ⅳ). The differences in survival rate between BFM 90 group and CHOP group, CHOP+HD MTX group were both significant (P=0.013, and P=0.034). CONCLUSION: BFM 90 regimen can greatly improve the survival rate of children and adolescents with B NHL, especially of patients with advanced NHL. CHOP, and CHOP+HD MTX regimens work better for the early stage patients, but produce low survival rate for patients with advanced NHL. A high intensive chemotherapy like BFM 90 regimen is necessary for chidren and adolescents with advanced B NHL.