[Outcome of children with T cell acute lymphoblastic leukemia treated with Chinese Children Leukemia Group acute lymphoblastic leukemia (CCLG-ALL) 2008 protocol].

Objective: To evaluate the efficacy of the Chinese Children's Leukemia Group (CCLG) acute lymphoblastic leukemia (ALL) 2008 protocol (CCLG-ALL 2008) in the treatment of children's T-cell acute lymphoblastic leukemia (T-ALL). Methods: Clinical characteristics and outcomes of 84 newly diagnosed T-ALL children (63 males and 21 females) treated with CCLG-ALL 2008 protocol from April 2008 to April 2015 in the Department of Pediatric Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences were analyzed retrospectively. Kaplan-Meier analysis was used to evaluate the overall survival (OS) and event free survival (EFS), and COX regression was used to evaluate the influencing factors of OS and EFS. Results: (1) Baseline data: 84 children were included, 56 cases (67%) of children were younger than 10 years old. Patients whose white blood cell count≥50×10(9)/L ranked 70% (59/84). Karyotype: 58% (49/84) with normal karyotype, 10% (8/84) with abnormality of chromosome 11, 8%(7/84) with abnormality of chromosome 9, 2%(2/84) with abnormality in both chromosome 11 and chromosome 9, 8% (7/84) with other complex karyotypes. Fusion gene: 33%(28/84) were SIL-TAL1 positive. The patients were grouped by CCLG-ALL 2008 risk score, 40% (34/84) were in the intermediate risk group and 60% (50/84) in the high risk group. (2) Treatment efficacy: 84 cases were followed up until May 30, 2018. The follow-up time was 42.0 (0.3-120.0) months. The sensitivity rate of prednisone treatment was 56% (47/84); the complete response (CR) rate after the induction therapy of vincristine+daunoblastina+L-asparaginase+dexamethasone (VDLD)(d 33) was 88% (74/84); the total CR rate after VDLD induction combined with cyclophosphamide+cytarabine+6-mercaptopurine (CAM) treatment (d80) was 94% (79/84); the recurrence rate was 24% (20/84). Among the 20 recurrent cases, there were 13 cases (65%) with ultra-early recurrence (within 18 months after diagnosis), 6 cases (30%) with early recurrence (18 to 36 months after diagnosis); 1 patient (5%) with late recurrence (over 36 months after diagnosis). During the follow-up period, twenty-eight children (33%) died (22 cases with recurrence or suspending treatment without remission, 2 cases with infection, 1 case of sudden death in chemotherapy, 1 patient failed in transplantation, 1 patient with severe cirrhosis, and 1 patient with unknown cause). (3) Kaplan-Meier analysis: the 5-year OS and EFS of the 84 children were (63±6)% and (60±6)% respectively. (4) Efficacy in different risk groups: prednisone sensitivity rates in the two different risk groups were 100% (34/34) and 26% (13/50), respectively (χ(2)=3.237, P<0.05). The CR rates at the end of VDLD induction therapy (d 33) were 100% (34/34) and 80% (40/50), respectively (χ(2)=2.767, P<0.05). The recurrence rate of children in the two groups was 12% (4/34) and 32% (16/50), respectively (χ(2)=4.245, P<0.05).The mortality rates of the two groups were 21% (7/34) and 42% (21/50), respectively (χ(2)=3.198, P<0.05). Kaplan-Meier analysis showed that the 5-year OS of the two groups were (77±7)% and (53±8)%; and the 5-year EFS of the two groups were (75±8)% and (49±8)% (χ(2)=4.235, 3.875, both P<0.05) . (5) COX multivariate regression analysis showed that the classification of risk according to CCLG-ALL 2008 was an important factor influencing the prognosis of children with T-ALL (OR=3.313, 95% CI 1.165-9.422, P=0.025). Conclusions: The results of the risk group treatment according to the CCLG-ALL 2008 protocol showed that the long-term survival of children with middle risk was significantly better than that of children at high risk.目的： 评价中国儿童白血病组织（CCLG）急性淋巴细胞白血病（ALL）2008方案（CCLG-ALL 2008）对儿童急性T淋巴细胞白血病（T-ALL）的临床疗效。 方法： 回顾性分析中国医学科学院血液病医院（血液学研究所）儿童血液病诊疗中心2008年4月至2015年4月采用CCLG-ALL 2008方案治疗的初诊T-ALL患儿84例（男63例、女21例）的临床特点、疗效，采用Kaplan-Meier分析评估患儿总生存率（OS）和无事件生存率（EFS），采用COX回归模型评估OS、EFS的影响因素。 结果： （1）一般特征：84例患儿中发病时年龄<10岁者56例（67%）；初诊时外周血白细胞计数（WBC）≥50×10(9)/L者70%（59/84）；正常核型58%（49/84），含有11号染色体异常10%（8/84），含有9号染色体异常8%（7/84），既含有11号染色体异常又含有9号染色体异常2%（2/84），其他复杂核型8%（7/84）；SIL-TAL1阳性者33%（28/84）；CCLG-ALL 2008危险度分组，中危组40%（34/84），高危组60%（50/84）。（2）疗效反应：截至2018年5月30日，随访时间42.0（0.3~120.0）个月。泼尼松治疗敏感率56%（47/84）；长春新碱+柔红霉素+门冬酰胺酶+地塞米松（VDLD）诱导治疗结束（第33天）完全缓解（CR）率88%（74/84）；VDLD诱导治疗及环磷酰胺+阿糖胞苷+6-巯基嘌呤（CAM）治疗结束后（第80天）总CR率94%（79/84）；复发率24%（20/84），20例复发患儿中超早期复发13例（65%）、早期复发6例（30%）、晚期复发1例（5%）。随访期间死亡28例，总病死率33%，其中因本病复发或未缓解导致死亡22例，因化疗后并发严重感染导致死亡2例，化疗中猝死1例，移植失败导致死亡1例，化疗后重度肝硬化导致死亡1例，死因不详1例。（3）Kaplan-Meier分析84例患儿5年OS、EFS分别为（63±6）%和（60±6）%。（4）不同危险组疗效：中、高危两组患儿泼尼松敏感率分别为100%（34/34）和26%（13/50）（χ(2)=3.237，P<0.05）；VDLD诱导治疗结束（第33天）CR率分别为100%（34/34）和80%（40/50）（χ(2)=2.767，P<0.05）；两组患儿复发率分别为12%（4/34）和32%（16/50）（χ(2)=4.245，P<0.05）；两组患儿病死率分别为21%（7/34）和42%（21/50）（χ(2)=3.198，P<0.05）。Kaplan-Meier分析中危和高危两组患儿5年OS分别为（77±7）%和（53±8）%，5年EFS分别为（75±8）%和（49±8）%（χ(2)=4.235、3.875，P均<0.05）。（5）COX多因素回归分析显示，危险度分组的划分是T-ALL患儿预后的重要影响因素（OR=3.313，95%CI：1.165~9.422，P=0.025）。 结论： 按照CCLG-ALL 2008方案进行危险度分组治疗，中危组T-ALL患儿的长期生存明显优于高危组。.