儿童急性淋巴细胞白血病生存率、缓解率、复发率和死亡率的多因素分析

发布时间：2018-07-28 16:52

【摘要】：目的：采用回顾性队列研究方法，收集整理急性淋巴细胞白血病（ALL）患儿的临床症状、体征、实验室检查结果和生存情况。通过对其入选的22个研究指标进行统计学分析，计算ALL患儿的无事件生存率，探讨研究指标对无事件生存时间、缓解率、复发率和死亡率的影响。为更科学的判断儿童ALL的预后，正确的评估ALL患儿的危险度，选择合理的个体化化疗方案提供理论依据。方法：回顾性的分析2006年01月01日至2012年01月01日于河北医科大学第二医院小儿内科血液专业组住院治疗的132例ALL患儿。 1、纳入标准：①年龄≤14岁。②符合儿童ALL诊断标准。诊断标准依据《儿童急性淋巴细胞白血病诊疗建议（第三次修订草稿）---2006年》或2010年《儿童急性淋巴细胞白血病临床路径（2010年版）》。排除标准：未经我院首诊、初治或治疗未满一个疗程的ALL患儿。 2、设计病史摘录表，系统摘录ALL患儿的性别、发病年龄、初诊时外周血白细胞的数目（WBC）、血红蛋白的含量(HGB)、血小板的数目(PLT)、是否有幼稚细胞、是否有中枢神经系统白血病（CNSL）或睾丸白血病、免疫学分型、融合基因(BCR/ABL)、肝肿大、脾肿大、淋巴结肿大、泼尼松诱导试验、第19天（D19）骨髓形态学检查、第33天（D33）骨髓形态学检查、肝损伤、肺损伤、治疗过程中感染、输注血液制品、治疗过程中的依从性、乳酸脱氢酶（LDH）和治疗方案共22个研究指标。 3、设计随访表，收集统计ALL患儿的生存情况并计算生存时间。 4、分组整理数据：性别（男；女）、年龄（1岁或10岁；1岁-10岁）、初诊时外周血WBC（＜50×10~9/L；(50-100)×10~9/L；≥100×10~9/L）、HGB（＜60g/L；≥60g/L）、PLT（＜20×10~9/L；≥20×10~9/L）、幼稚细胞（无；有）、免疫学分型（B系；T系）、融合基因（BCR/ABL）（阴性；阳性）、CNSL或睾丸白血病（否；是）、肝肿大（距离肋缘下的距离）（＜5cm；≥5cm）、脾肿大（距离肋缘下的距离）（＜5cm；≥5cm）、淋巴结肿大（未触及；颈部、腋窝、腹股沟淋巴结可触及肿大）、泼尼松诱导试验（良好；不良）、D19骨髓形态学检查（原始淋巴细胞+幼稚淋巴细胞）（＜5%；≥5%）、D33骨髓形态学检查（原始淋巴细胞+幼稚淋巴细胞）（＜5%；≥5%）、化疗过程中感染（否；是）、肝损伤（否；是）、肺损伤（否；是）、输注血液制品（否；是）、治疗过程中的依从性（治疗是否中断3月以上）（否；是）、LDH（＜240u/L；≥240u/L）和治疗方案（2006方案；临床路径；特殊方案）。 5、统计学分析：所有数据均采用SPSS17.0统计学软件进行统计学分析。其中采用Kaplan-Meier法计算三年、五年无事件生存率；采用Log-Rank检验进行生存曲线比较；采用COX风险比例回归模型进行单因素分析，筛选无事件生存时间的影响因素，进一步建立COX风险比例回归模型进行多因素分析，进一步筛选无事件生存时间的影响因素；采用Logistic回归分析各个研究指标对缓解率、复发率或死亡率的影响；计量资料均数计算采用t检验；P0.05表示差异有统计学意义。结果：收集病例共132例，其中包括无事件生存105例(诱导治疗未缓解2例，再次诱导治疗均达缓解)，，复发19例，死亡8例。缓解率为98.48%，复发率为14.39%，死亡率为6.07%。三年无事件生存率为（74.9±0.05）%，五年无事件生存率为（63.3±0.07）%。依据危险度分级将132例ALL患儿划分为低危组、中危组和高危组。其中低危组52例，中危组42例，高危组38例。低危组三年无事件生存率为（87.2±0.06）%，五年无事件生存率为（71.5±0.10）%。中危组三年无事件生存率为（67.6±0.10）%，五年无事件生存率为（67.6±0.10）%。高危组三年无事件生存率为（63.1±0.10）%，五年无事件生存率为（50.5±0.14）%。不同危险度分组的ALL患儿进行生存曲线比较，差异（P=0.023）存在统计学意义。并且随着危险度的提高，ALL患儿的无事件生存率下降。COX风险比例回归模型单因素筛选结果显示：免疫学分型（P=0.005）和依从性(P=0.046)对ALL患儿的无事件生存时间有影响。COX风险比例回归模型多因素分析结果显示：免疫学分型（P=0.005）和依从性(P=0.045)为独立的预后影响因素。 Logistic回归分析结果显示：治疗过程中输入血液制品（P=0.040）可以提高缓解率；融合基因（BCR/ABL）阳性（P=0.004）增加复发率；22个研究指标均对死亡率无影响。132例ALL患儿在化疗过程中感染者45例，感染率为34.09%。在感染的ALL患儿中，以呼吸道为主（36例），占80.43%。4例重症感染ALL患儿均死亡，占ALL死亡患儿的50%。结论： 1、儿童ALL的危险度级别越高，无事件生存率越低。 2、免疫学分型和依从性为独立的预后影响因素。B-ALL患儿的无事件生存率明显的高于T-ALL患儿，坚持规范化治疗是预后良好的重要保证。 3、融合基因（BCR/ABL）阳性增加复发率。 4、治疗过程中输入血液制品可以提高缓解率。 5、儿童急性淋巴细胞白血病化疗过程中的感染以呼吸道为主，重症感染易导致死亡。
[Abstract]:Objective: to collect and collate the clinical symptoms, signs, laboratory results and survival conditions of children with acute lymphoblastic leukemia (ALL) by retrospective cohort study. By statistical analysis of the 22 research indicators selected, the non event survival rate of children with ALL was calculated, and the time of life free survival and mitigation were discussed. The effect of rate, recurrence rate and death rate. To judge the prognosis of ALL in children more scientifically, to evaluate the risk of ALL in children correctly, and to provide the theoretical basis for selecting reasonable individualized chemotherapy scheme.
Methods: a retrospective analysis of 132 ALL children hospitalized in the pediatric department of pediatric department of Hebei Medical University, second hospital from 01 from 01 months to 2012, 2012, 2006.
1, the criteria were included: (1) age less than 14 years of age. (2) compliance with children's ALL diagnostic criteria. Diagnostic criteria were based on the recommendations of children's acute lymphoblastic leukemia (Third Revised Draft) ---2006 > or in 2010 < the clinical pathway of childhood acute lymphoblastic leukemia (2010 Edition) >. ALL children of the course.
2, an excerpt of medical history was designed to systematically extract the sex of ALL children, the age of onset, the number of white blood cells in peripheral blood (WBC), the content of hemoglobin (HGB), the number of platelets (PLT), whether there were naive cells, whether there were central nervous system leukemia (CNSL) or testicular leukemia, immunological typing, fusion gene (BCR/ABL), hepatomegaly, and splenomegaly Large, lymph node swelling, prednisone induction test, nineteenth days (D19) bone marrow morphological examination, thirty-third days (D33) bone marrow morphology examination, liver injury, lung injury, treatment process infection, transfusion of blood products, treatment compliance, lactate dehydrogenase (LDH) and treatment regimen were 22 research indicators.
3, design follow-up table, collect statistics of ALL children's survival and calculate the survival time.
4, group sorting data: sex (male; female), age (1 years or 10 years old; 1 year old -10), WBC (< 50 x 10~9/L; (50-100) * * 10~9/L; > 100 * 10~9/L) at first visit, HGB (< 60g/L; > 60g/L), PLT (< 20 x 10~9/L; > 20 x 10~9/L), infant fine cell (B; Immune), fusion gene (negative; positive) CNSL or testicular leukemia (no; yes), hepatomegaly (distance from the ribbed margin) (< 5cm; > 5cm), splenomegaly (distance from the ribbed margin) (< 5cm; > 5cm), lymph node enlargement (unpalpable; neck, axillary, inguinal lymph node palpable), prednisone induction test (good; bad), D19 bone marrow morphology examination (primitive lymph fines) Cell + infantile lymphocyte) (< 5%; > 5%), D33 bone marrow morphological examination (primary lymphocyte + naive lymphocyte) (< 5%; > 5%), infection (no; yes), liver injury (no; yes), lung injury (no; yes), transfusion of blood products (no; yes), compliance in the course of treatment (whether the treatment was interrupted by March) (no; yes), LDH (no), 240u/L; > 240u/L) and treatment plan (2006 scheme; clinical pathway; special scheme).
5, statistical analysis: all data were statistically analyzed using SPSS17.0 statistics software. Among them, Kaplan-Meier method was used to calculate three years and five years of no event survival rate; Log-Rank test was used to compare the survival curve; COX risk ratio regression model was used for single factor analysis to screen the influence factors of the event free survival time. The COX risk proportional regression model was further established for multi factor analysis, and the influence factors of the event free survival time were further screened. Logistic regression analysis was used to analyze the effect of each research index on the rate of remission, the recurrence rate or the mortality, and the average number of measurement data was calculated by t test, and P0.05 indicated that the difference was statistically significant.
Results: a total of 132 cases were collected, including 105 cases of non event survival (2 cases without remission, 2 remission), 19 cases of recurrence, 8 cases of death. The remission rate was 98.48%, the recurrence rate was 14.39%, the mortality rate was (74.9 + 0.05)% (74.9 + 0.05)%, and the mortality rate of five years was (63.3 + 0.07)%. According to the risk degree. 132 children with ALL were divided into low risk group, middle risk group and high risk group, including 52 cases in low risk group, 42 cases in middle risk group and 38 cases in high risk group. The three year survival rate of low risk group was (87.2 + 0.06)%, and the survival rate of five years was (71.5 + 0.10)%. The non event survival rate in the middle risk group three years was (67.6 + 0.10)%, and the non event survival rate was (87.2)%. The three year non event survival rate of the high-risk group was (63.1 + 0.10)%, and the five year event free survival rate was (50.5 + 0.14)%. The survival curve of ALL children with different risk groups was compared, the difference (P=0.023) was statistically significant. And with the increase of risk, the survival rate of ALL children decreased by the.COX risk proportion regression model single factor screening knot. The results showed that immunological typing (P=0.005) and compliance (P=0.046) had influence on the event free survival time of children with ALL. The multifactor analysis of the.COX risk proportional regression model showed that immunological typing (P=0.005) and compliance (P=0.045) were independent prognostic factors. The results of Logistic regression analysis showed that the input of blood in the treatment process was in the course of treatment. P=0.040 could increase the remission rate, and the fusion gene (BCR/ABL) positive (P=0.004) increased the recurrence rate; the 22 study indexes had no effect on the mortality of.132 cases in children with ALL in the chemotherapy process, the infection rate was 34.09%. in the infected ALL children, and the respiratory tract was the main (36 cases), and all of the children with severe infection of ALL in 80.43%.4 cases were all dead. 50%. in children with ALL death
Conclusion:
1, the higher the risk level of children's ALL, the lower the event free survival rate.
2, immunological classification and compliance are independent prognostic factors of.B-ALL children's non event survival rate is significantly higher than that of children with T-ALL, and adherence to standardized treatment is an important guarantee for good prognosis.
3, the fusion gene (BCR/ABL) positive increased the recurrence rate.
4, blood products can increase the remission rate during treatment.
5, the infection of children with acute lymphoblastic leukemia during chemotherapy is mainly respiratory tract, and severe infection can easily lead to death.
【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R733.7

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