| BackgroundAcute lymphoblastic leukemia(ALL) is the most common hematologic malignancy in children, which is currently one of the best curative effect and cure rate of malignant diseases. With the improvement of remission rate and significant extension of survival in ALL, while the incidence rate of central nervous system leukemia(CNSL) has also increased. CNSL is caused by the infiltration of leukemic cell in the central nervous system(CNS). Once CNSL developed in childhood ALL, it will increase the difficulty in future treatment and also predicts a poor prognosis. As is one of the biggest obstacles in healing childhood leukemia, accurate stratification diagnosis and precise risk assessment and targeted prevention of CNSL have became extremely important parts in the modern system of the comprehensive treatment of childhood leukemia.Though lumbar puncture is the common method of operation for the clinical diagnosis, prevention and treatment of CNSL, it may resulted in traumatic lumbar puncture(TLP) because of the iatrogenic LP injury in the procedure. Recently, several related reports concerning the risk factors of TLP, the correlation between the occurrence of CNSL and TLP and the prognostic relevance of TLP are still controversial.In this retrospective study, we enrolled newly diagnosed patients with ALL from January 2010 to December 2014 in our hospital pediatrics department. Our study will provide a clinical basis for the further research in early diagnosis, prevention and treatment field of childhood CNSL.Objective The aim of this study is to gain an insight into the clinical characteristics of childhood ALL leukemia complicated by CNSL, and to estimate the factors that leading to CNSL, and to evaluate the prognosis of CNSL. Besides, this study was also performed to determine the critical platelet count which would predict a TLP, the risk factors associated with TLP at diagnosis and the effect of TLP on prognosis in childhood ALL.Methods A retrospective analysis was performed from the medical records of 106 children with ALL who were diagnosed and treated from January 2010 to December 2014 in our hospital pediatrics department. 1. Chi-square test or Fisher probabilities test are used to analyze the relation between the incidence of CNSL and the factors such as sex, age, white blood cell(WBC) in peripheral at preliminary diagnosis, CNS2, ALL clinical risk classification, immunological typing, traumatic lumbar puncture. 2. According to cerebrospinal fluid cell morphology at first diagnosis, ALL patients will be divided into four types, namely CNS1, CNS2, CNS3, TLP. Chi-square test or t test are used to analyze the risk factors associated with TLP at diagnosis, and a receiver operating characteristic curve is constructed to determine the critical platelet count which would predict a TLP. Besides, the Kaplan-Meier method and log-rank test are also adopted to estimate the survival rate and compare the survival difference among the four types patients.Results 1. A total of 106 patients were treated for ALL during the study period, of which 12cases relapse(11.3% recurrence rate) in total, among whom 6 had isolated bone marrow relapse, 3 had isolated CNS relapse, 1 had isolated testicular relapse, and 2 had combined CNS and bone marrow relapse. CNSL occurred in 10 patients, and the incidence was 9.4% in total ALL patients. The average age was 71.4 ± 15. 6 months(range: 6.2-156). 5 patients occurred CNSL at the diagnose of ALL, while other 5 cases in the treatment process of ALL. Among 10 cases of CNSL patients, of which 3 cases occurred repeatedly CNS relapse and 2 patients combined with bone marrow relapse. At follow up of 10 CNSL patients, among whom 4 are still in maintaining chemotherapy, 2 had stopped therapy, 3 died, and 1 of giving up treatment was lost follow-up. 2. When compared the age and sex of the patients' who occur CNSL with those who did not, the difference was not statistically significant(P>0.05). The TLP and CNS2 at diagnose respectively compared with CNS1 did not affect the occurrence of CNSL(P>0.05). The association between the incidence of CNSL and the factors such as ALL clinical risk classification, immunological typing and white blood cell in peripheral at preliminary diagnosis: the incidence of CNSL with high risk ALL patients was significantly higher than the low and median risk(P<0.05); the incidence of CNSL with T-ALL patients was significantly higher than B-ALL(P<0.05); patients with WBC?50×109/L in peripheral blood at preliminary diagnosis have a significantly higher CNSL incidence than patients with WBC<50×109/L(P<0.05); patients with WBC?100×109/L have a significantly higher CNSL incidence than patients with WBC<100×109/L(P<0.05). 3. The age, sex and median WBC in peripheral did not affect the occurrence of TLP(P>0.05). Median platelet count in 85 patients with ATLP and in 21 patients with TLP was 72.50±69.53×109/L and 31.10±19.82×109/L(P < 0.05). A receiver operating characteristic curve was constructed for predicting the risk of TLP based on platelet count. Area under the curve was 0.75(95% confidence interval 0.64–0.86, P<0.05). A Platelet count of 34× 109/L at the time of LP had a Sensitivity of 76% and specificity 66% specificity in predicting a TLP.4. The mean follow-up duration of the total 106 ALL patients was 37.06 ± 19.90 months(range: 1–72). CNS status at diagnosis based on the cytomorphology examination in CSF was CNS 1: 69(65.1%), CNS 2: 11(10.4%), CNS 3: 5(4.7%), TLP: 21(19.8%) patients. The estimated 5-year event-free survival ±standard error for 106 ALL patients was 73.6% ±5.7%. The estimated 3-years EFS of patients with CNS 1, CNS 2, CNS 3 and TLP was 82.8%±4.8%, 90.9±8.7%, 60.0%±21.9%, 74.7%±9.9% respectively. Compared the EFS difference in CNS3 group with CNS1 group, there was a statistically significant difference(P<0.05).Conclusions 1. 12 patients relapsed in total ALL patients and the recurrence occurred at the bone marrow, CNS, testicular. The incidence of CNSL was 9.4% in this study. Patients can developed CNSL both at the diagnose of ALL and in the process of ALL therapy. Among 10 cases of CNSL patients, of which 3 cases occurred repeatedly CNS relapse and 2 patients combined with bone marrow relapse. As a whole, patients who developed CNSL have an inferior prognosis comparatively. 2. Factors such as ALL risk classification for high-risk, immunologic classification for T cell, the peripheral WBC count?50×109 / L or WBC?100×109 / L can increase the incidence of CNSL. 3. Platelet counts<34×109 / L are significantly associated with risk of TLP. Efforts should be made to ensure a platelet count >34,000/?L prior to doing an LP to avoid a TLP. 4. In our study, CNS 2 and TLP did not contribute to inferior EFS and increased the incidence of CNSL. The EFS in CNS 3 group was significantly lower than CNS1, indicating a poor prognosis when accompanied by CNS infiltration at diagnosis. |
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