影響兒童急性淋巴性白血病預後因子的探討

一、背景急性淋巴性白血病是18歲以下兒童最常見的惡性疾病。在台灣，每年約有200位新發病的兒童，其好發年齡在2到5歲。隨著醫療水準持續而穩定的進步，在世界各醫療先進國家，已有超過80%的兒童急性淋巴性白血病患者可以達到痊癒。如何持續提高治癒率，同時減少因為治療而帶來的毒性與後遺症，成了現今治療兒童急性淋巴性白血病，最重要的課題。隨著醫療照護品質的提升，使得病人可以接受更強的化學治療，因此使得過去一些有意義的預後因子，其影響變得不再顯著。另一方面，診斷工具與技術的不斷進展，出現了許多新的預後因子，改變了分群治療的選擇標準以及治療方式，若有越多有意義且具有指標性的預後因子，則在臨床上越能提供病人適切的治療方案，進一步提高治癒率，並減少治療所帶來的毒性，提升病人的生活品質。二、研究方法與病人在西元2000年6月1日到2008年10月31日期間，共有84位18歲以下於彰化基督教醫院新診斷為急性淋巴性白血病的患者。其中68位病患的臨床資訊及相關生物學特徵可供分析。所有病人的治療，皆依據台灣兒童癌症治療群的治療計畫，並根據他們的臨床表徵，白血病細胞的生物特徵，以及他們對化學治療初期的反應，分為標準危險群、高危險群、及最高危險群。三、結果 68位病人中有47位男性及21位女性，診斷年齡中位數為5.3歲，年齡範圍為0.7歲到17.9歲，追蹤時間中位數為42.4個月(範圍:1.2個月到107.4個月)。所有病人的5年整體存活率為87.2+4.3%，5年無事件存活率為86.2+4.3%。各分群的5年無事件存活率分別為：標準危險群患者(21位)，100%，高危險群患者(22位)，90.9+6.1%，最高危險群患者(25位)，70.4+9.4%，(log rank, P值=0.016) 依據單變異分析(univariate analysis)的結果，診斷時的年齡大於10歲，最高危險群，診斷時的周邊血液白血球細胞數目>100x109 /L，肝臟大於5公分(右側肋骨下緣)，脾臟大於5公分(左側肋骨下緣)，具費城染色體等因子，對5年無事件存活率而言，是預後不佳的預測指標。其中，診斷時年齡大於10歲，是5年無事件存活率不佳的獨立預後因子。四、結論在本研究中屬於最高危險群的患者比例較高，雖然5年無事件存活率已達七成，卻仍有不小比例的患者治療失敗。更謹慎的分群評估，更精確的分子生物學檢查，以及對致病機轉更深入的了解，可以提升預後因子以及抗癌藥物在臨床上的運用，進一步提高最高危險群的兒童急性淋巴性白血病患者的治癒率。

關鍵字

急性淋巴性白血病；存活率；預後因子

並列摘要

Background Acute lymphoblastic leukemia, a malignant disorder of lymphoid progenitor cells, affects both children and adults, with peak prevalence between the ages of 2 and 5 years. Approximately 200 children are diagnosed with acute lymphoblastic leukemia each year in Taiwan. Steady progress in development of effective treatments has led to a cure rate of more than 80% in children. The focus of modern treatment protocols for childhood acute lymphoblastic leukemia has turned increasingly to improving the quality of life of long-term survivors. We evaluate the significance of prognostic factors on survival in children with acute lymphoblastic leukemia. Patients and Methods From June 2000 to October 2008, 84 children and adolescents, 18 years of age or younger, with newly diagnosed acute lymphoblastic leukemia were enrolled in TPOG (Taiwan Pediatric Oncology Group) protocols for childhood acute lymphoblastic leukemia at Chang-Hua Christian hospital. Sixty-eight of 84 patients were evaluable for the study. Patients were stratified into three risk groups---standard risk (SR), high risk (HR), and very high risk (VHR), based on the presenting clinical features, biologic features of leukemia cells, and initial response to treatments. Results There were 47 boys and 21 girls. Median age at diagnosis was 5.3 years with the range of 0.7 to 17.9 years. At a median follow-up of 42.4months (range from 1.2 months to 107.4months), the 5-year overall survival (OS) and event-free survival (EFS) of all patients were 87.2+4.3(SE)% and 86.2+4.3%, respectively. The 5-year EFS was 100% for SR patients (n=21), 90.9+6.1% for HR patients (n=22), and 70.4+9.4% for VHR patients (n=25)(log rank p=0.016). Age over 10 years at diagnosis, very high risk group, hepatomegaly and splenomegaly, positive Philadelphia chromosome and white blood cell count at diagnosis over 100x109 /L, were significant adverse prognostic factors to EFS. By multivariate analysis applied to the entire cohort, only the age over 10 years at diagnosis was independently associated with an inferior treatment outcome. Conclusions In our study, a large number of relapses appear not to be predictable with use of currently available prognostic factors, especially in those with very high risk group. Better identification of biologic defined risk groups and their risk-adapted treatment by incorporating minimal residual leukemia measurement and host pharmacogenetic determination into existing risk classification system may improve the cure rate of patients at true high risk of relapse.

並列關鍵字

acute lymphoblastic leukemia ； survival ； prognostic factor

參考文獻

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影響兒童急性淋巴性白血病預後因子的探討

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