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作者：Janis C. Kelly  
出處：WebMD醫學新聞

　　April 1, 2010 — 發生化療引起之發熱性嗜中性球減少症(febrile neutropenia，FN)的癌症病患，有發生侵犯型感染的風險，標準治療是緊急住院以及靜脈注射抗生素，但是，如果可以分辨哪些是低風險者，病患就可以免去此項治療。
　　
　　新版風險適應治療指引是為成人而發展，但是，對於小兒病患如何預測此不良事件(AE)的風險，迄今尚無共識。不過，目前已朝此目標邁進一步，Roland A. Ammann醫師與瑞士小兒腫瘤小組(SPOG)的研究夥伴，發展了一個新的風險評分系統，線上發表於3月15日的臨床腫瘤期刊(Journal of Clinical Oncology)。
　　
　　來自瑞士柏恩大學小兒血液腫瘤科的Ammann醫師與瑞士和德國的8個醫學中心的腫瘤科醫師合作，發展出一套新的不良事件預測方法，他們的前瞻「SPOG?2003 FN」研究包括了在「非骨髓破壞式化療」之後發生發熱性嗜中性球減少症的1-18歲癌症病患，他們分析了206名病患的423次發熱性嗜中性球減少症發作。
　　
　　在發作時，病患接受了體檢、全血球計數(包括各種白血球數量)以及血液培養，並且住院接受經驗性靜脈注射廣效抗生素治療，其他治療方式由主治醫師決定。
　　
　　在8-24小時住院治療之後，由小兒腫瘤專科醫師再度評估每位病患。
　　
　　不良事件報告直到停用抗生素治療、以及嚴重嗜中性白血球減少緩解7天之後。
　　
　　可以用來預測不良事件的4個變項，包括之前的化療強度超過急性淋巴性白血病維持治療(重要性= 4)、血紅素值大於等於90 g/L (重要性= 5)、白血球數量小於0.3 g/L (重要性= 3)、血小板數量小於50 g/L (重要性= 3)，這些重要性分數之總和即為此預測分數。
　　
　　發作時計算的分數並未準確預測之後的不良事件，但是，分數大於等於9分的病患在再度評估時(住院照護8-24小時之後)，後來發生不良事件的風險增加。
　　
　　研究者對其他已經發表的風險預測規則檢測此一評估分數，發現它比較準確，整體敏感度為92%、35%屬於低風險，專一度為45%，陰性預測值為93%。
　　
　　增加各種白血球數量資料並不會改善預測準確度。
　　
　　作者們結論表示，我們發展的這個風險分數使用4個容易評估的特徵，根據病患病史以及發作時的血球數量，但是不根據各種白血球數量，在不超過24小時的住院處置之後，再度評估預測未來的不良事件風險，會比發生發熱性嗜中性球減少症當下的評估更佳，這個分數可以準確分辨未來發生不良事件風險較高的病患。
　　
　　不過，在這些研究對象中，這個分數只預測了3件致命不良事件中的1件，這3件致命事件的預測分數分別是5分、4分、10分。
　　
　　Medscape Oncology邀請同樣研究癌症孩童發熱性嗜中性球減少症的Stephane Paulus醫師對此研究發表評論(Adv Exp Med Biol. 2009;634:185-204)。英國利物浦Alder Hey兒童醫院小兒感染症顧問Paulus醫師表示，這是一個不錯的嘗試，由此領域的一些有經驗的專家，盡可能安全地定義發熱性嗜中性球減少症低風險的孩童。
　　
　　Paulus醫師指出，雖然由一名小兒腫瘤科醫師在8-24小時再度評估病童，但是未同時再度檢查發炎標記，如C反應蛋白(CRP)。
　　
　　Paulus醫師表示，其他研究顯示，在住院時以及24小時之後(因為這些標記需要時間產生反應)併用發炎標記如PCT (血小板血比容)和介白素-8，加上CRP，可幫助定義低風險與高風險組，納入這些標記加上重複臨床檢查可以促進研究結果。
　　
　　Paulus醫師指出，他們結論表示，他們的評分系統準確地預測不良事件，不過，敏感度只有92%且陽性預測值只有40%，所以，這個研究方法在找出那些低風險方面還過得去，但是還不足以好到正確預測不良事件，另外，再次強調，這個分數只有預測3件致命不良事件中的1件。
　　
　　Ammann醫師強調，在考慮臨床運用此一不良事件預測分數方式之前，需有前瞻研究確認，根據Paulus醫師表示，這個分數有其可用之處，但是還沒有準確到可以在臨床實務安全地辨識低風險族群。
　　
　　Paulus醫師表示，這個研究的確在這領域增加了一些不錯的資料，但是還不足以改變它。
　　
　　Ammann醫師以及瑞士柏恩大學兒童醫院的Christoph Aebi醫師支持該研究，Ammann醫師以及 Paulus醫師皆宣告沒有相關財務關係。
　　
　　J Clin Oncol. 線上發表於2010年3月15日。


Tool Might Help Predict Adverse Events in Children With Cancer

By Janis C. Kelly
Medscape Medical News

April 1, 2010 — Cancer patients who develop chemotherapy-induced febrile neutropenia (FN) are at risk for invasive infections, so standard treatment is emergency hospitalization and intravenous antimicrobial therapy. But patients could be spared this treatment if it were possible to identify those who were at low risk.

New risk-adapted treatment guidelines have been developed for adults, but so far no consensus has emerged on how to predict adverse-event (AE) risk in pediatric patients. A step toward this, however, is a new risk-scoring system, developed by Roland A. Ammann, MD, and colleagues in the Swiss Pediatric Oncology Group (SPOG), and reported online March?15 in the Journal of Clinical Oncology.

Dr. Ammann, from the Department of Pediatric Hematology/Oncology at the University of Bern in Switzerland, collaborated with oncologists from 8 medical centers in Switzerland and Germany to develop the new AE predictive measure. Their prospective SPOG?2003 FN study included cancer patients 1 to 18 years of age presenting with FN after nonmyeloablative chemotherapy. They analyzed 423 episodes of FN in 206 patients.

At presentation, patients underwent physical examination, complete blood count (including differential leukocyte count), and blood cultures, and were hospitalized and treated with empirical intravenous broad-spectrum antimicrobial therapy. Other procedures were determined by the treating physician.

After 8 to 24 hours of inpatient therapy, each patient was reassessed by a board-certified pediatric oncologist.

AEs were reported until 7 days after the discontinuation of antimicrobial therapy and the resolution of severe neutropenia.

The 4 variables that were useful for predicting AEs were preceding chemotherapy more intensive than acute lymphoblastic leukemia maintenance (weight?= 4), hemoglobin of 90?g/L or more (weight?= 5), leukocyte count of less than 0.3?g/L (weight?= 3), and platelet count of less than 50?g/L (weight?= 3). The score was the sum of these weights.

The score calculated at presentation did not accurately predict subsequent AEs, but patients with a score of 9 or more at reassessment (after 8 to 24 hours of hospital care) were at increased risk for future AEs.

The researchers tested this score against other published risk-prediction rules and found that it was more accurate. Overall sensitivity was 92%, with 35% of episodes classified as low risk. Specificity was 45%, and negative predictive value was 93%.

Adding differential leukocyte count data did not improve predictive accuracy.

The authors conclude that the "risk score developed here is constructed using 4 characteristics easily accessible, based on patient history and a blood cell count at presentation, but not on a differential leukocyte count. The prediction of risk for future AEs at reassessment, after 24 hours or less of inpatient management, is better than that at presentation with FN. This score accurately identifies patients at high risk for future AEs."

However, the score predicted only 1 of the 3 fatal AEs in the study population. One of these fatalities had a prediction score of 5, one had a score of 4, and one had a score of 10.

To comment on the study, Medscape Oncology asked Stephane Paulus, MD, who has also studied FN in children with cancer (Adv Exp Med Biol. 2009;634:185-204). Dr. Paulus, who is a pediatric infectious diseases consultant at Alder Hey Children's Hospital in Liverpool, United Kingdom, said; "This is another good attempt at trying to define as safely as possible a low-risk group of children with febrile neutropenia by a group with good experience in this field."

Dr. Paulus noted that although a pediatric oncologist reviewed the children at 8 to 24 hours, this was not accompanied by a second check of the inflammatory markers, in this case C-reactive protein (CRP).

"Other studies have shown the promise of using a combination of inflammatory markers, such as PCT (packed cell volume of platelets) and interleukin-8, in addition to CRP, at admission and then again at 24 hours (as these markers take time to 'react') to help define low- and high-risk groups. Including these markers along with a repeat clinical examination might have enhanced the study results," Dr. Paulus said.

"They conclude that their scoring system adequately predicts AEs. However, sensitivity was 92% and the positive predictive value was 40%. So the study was pretty decent at picking up those low risks but not [as good] at predicting the AEs correctly. But again, the score predicted AEs in only 1 of 3 episodes leading to death reported in this study," Dr. Paulus added.

Dr. Ammann stressed the importance of prospective validation studies before considering broad clinical application of this AE predictive score. According to Dr. Paulus, the score is somewhat useful but not accurate enough to safely identify a low-risk group in clinical practice.

"This does add some good data to the body of literature but does not revolutionize it," Dr. Paulus said.

The study was supported by Dr. Ammann and Christoph Aebi, MD, from the University Children's Hospital in Bern, Switzerland. Dr. Ammann and Dr. Paulus have disclosed no relevant financial relationships.

J Clin Oncol. Published online March?15, 2010.