利妥昔單抗聯合FC方案治療慢性淋巴細胞白血病的療效和安全性系統評價_《中國循證醫學雜志》

作者：

趙龍 ,  席亞明 , 郭敏 , 晁榮 , 靳蕊蕊

蘭州大學第一醫院血液科，血液學研究所（蘭州?730000）;

關鍵詞：

慢性淋巴細胞性白血病利妥昔單抗氟達拉濱環磷酰胺 Meta分析系統評價隨機對照試驗

DOI：

10.7507/1672-2531.20110221

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目的　系統評價利妥昔單抗與氟達拉濱和環磷酰胺（FC）組成的FCR方案對慢性淋巴細胞白血病（CLL）的治療效果和安全性。
方法　計算機檢索PubMed、Cochrane Library、SpringerLink、CNKI和CBM數據庫2000～2011年期間發表的關于FCR方案和FC方案比較治療CLL的隨機對照試驗（RCT）。由兩位研究者獨立進行文獻篩選、資料提取和質量評價后，采用RevMan 5.0軟件進行Meta分析。
結果　共納入3個RCT，共1 623例患者。Meta分析結果顯示：FCR方案與FC方案相比，兩者無進展生存期（P lt;0.001）、總體生存率［OR=1.94，95%CI（1.49，2.53），P lt;0.000 01］、完全緩解率［OR=2.54，95%CI（2.00，3.22），P lt;0.000 01］、Ⅲ/Ⅳ級中性粒細胞減少癥發生率［OR=1.60，95%CI（1.33，1.92），P lt;0.000 01］、總的Ⅲ/Ⅳ級不良反應發生率［OR=1.72，95%CI（1.35，2.20），P lt;0.000 1］差異均有統計學意義；而兩者部分緩解率［OR=0.74，95%CI（0.35，1.55），P=0.43］、Ⅲ/Ⅳ級血小板減少癥［OR=0.97，95%CI（0.74，1.27），P=0.83］、自身免疫性溶血性貧血［OR=0.86，95%CI（0.59，1.27），P=0.45］發生率差異均無統計學意義。
結論　利妥昔單抗聯合氟達拉濱和環磷酰胺組成的FCR方案可明顯延長CLL的無進展生存期，提高總體生存率和完全緩解率。但部分患者也會出現Ⅲ/Ⅳ級中性粒細胞減少癥、血小板減少癥、自身免疫性溶血性貧血、惡心嘔吐等不良反應。

引用本文： 趙龍,席亞明,郭敏,晁榮,靳蕊蕊. 利妥昔單抗聯合FC方案治療慢性淋巴細胞白血病的療效和安全性系統評價. 中國循證醫學雜志, 2011, 11(11): 1321-1326. doi: 10.7507/1672-2531.20110221 復制

1.	2 Ricci F, Tedeschi A, Morra E, et al . Fludarabine in the treatment of chronic lymphocytic leukemia: a review. Ther Clin Risk Manag , 2009, 5(1): 187-207.
2.	3 Wierda W, O'Brien S, Faderl S, et al . A retrospective comparison of three sequential groups of patients with Recurrent/Refractory chronic lymphocytic leukemia treated with fludarabine-based regimens. Cancer , 2006, 106(2): 337-345.
3.	4 Hallek M, Fischer K, Fingerle-Rowson G, et al . Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial. Lancet , 2010, 376(9747): 1164-1174.
4.	5 Eichhorst BF, Busch R, Hopfinger G, et al . Fludarabine plus cyclophosphamide versus fludarabine alone in first-line therapy of younger patients with chronic lymphocytic leukemia. Blood , 2006, 107(3): 885-891.
5.	6 Grever MR, Lucas DM, Dewald GW, et al . Comprehensive assessment of genetic and molecular features predicting outcome in patients with chronic lymphocytic leukemia: results from the US Intergroup Phase III Trial E2997. Journal of Clinical Oncology , 2007, 25(7): 799-804.
6.	8 Robak T, Dmoszynska A, Solal-Celigny P, et al . Rituximab Plus Fludarabine and Cyclophosphamide Prolongs Progression-Free Survival Compared With Fludarabine and Cyclophosphamide Alone in Previously Treated Chronic Lymphocytic Leukemia. Journal of Clinical Oncology , 2010, 28(10): 1756-1765.
7.	9 Flinn IW, Neuberg DS, Grever MR, et al. Phase III trial of fludarabine plus cyclophosphamide compared with fludarabine for patients with previously untreated chronic lymphocytic leukemia: US Intergroup Trial E2997. Journal of Clinical Oncology , 2007, 25(7): 793-798.
8.	10 Dretzke J, Barton P, Kaambwa B, et al . Rituximab for the treatment of relapsed/refractory chronic lymphocytic leukaemia. Health Technol Assess , 2010, 14(Suppl. 2): 19-26.
9.	11 O'Brien S, Osterborg A. Ofatumumab: a new CD20 monoclonal antibody therapy for B-cell chronic lymphocytic leukemia. Clin Lymphoma Myeloma Leuk , 2010, 10(5): 361-368.
10.	12 Byrd JC, Kipps TJ, Flinn IW, et al . Phase 1/2 study of lumiliximab combined with fludarabine, cyclophosphamide, and rituximab in patients with relapsed or refractory chronic lymphocytic leukemia. Blood , 2010, 115(3): 489-495.
11.	13 Wierda W, O'Brien S, Wen S, et al . Chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab for relapsed and refractory chronic lymphocytic leukemia. J Clin Oncol , 2005, 23(18): 4070-4078.
12.	14 Casak SJ, Lemery SJ, Shen YL, et al . U.S. Food and drug administration approval: rituximab in combination with fludarabine and cyclophosphamide for the treatment of patients with chronic lymphocytic leukemia. Oncologist , 2011, 16(1): 97-104.
13.	16 Dohner H, Fischer K, Bentz M, et al . p53 gene deletion predicts for poor survival and non-response to therapy with purine analogs in chronic B-cell leukemias. Blood , 1995, 85 (6): 1580-1589.
14.	17 Grever MR, Lucas DM, Dewald GW, et al . Comprehensive assessment of genetic and molecular features predicting outcome in patients with chronic lymphocytic leukemia: results from the US Intergroup Phase III Trial E2997. J Clin Oncol , 2007, 25 (7): 799-804.
15.	18 Dohner H, Stilgenbauer S, James MR, et al . 11q deletions identify a new subset of B-cell chronic lymphocytic leukemia characterized by extensive nodal involvement and inferior prognosis. Blood , 1997, 89(7): 2516-2522.
16.	19 Tsimberidou AM, Tam C, Abruzzo LV, et al . Chemoimmunotherapy may overcome the adverse prognostic significance of 11q deletion in previously untreated patients with chronic lymphocytic leukemia. Cancer , 2009, 115(2): 373-380.
17.	20 Schlette EJ, Admirand J, Wierda W, et al . p53 expression by immunohistochemistry is an important determinant of survival in patients with chronic lymphocytic leukemia receiving frontline chemo-immunotherapy. Leuk Lymphoma , 2009, 50 (10): 1597-1605.
18.	21 Moreno C, Villamor N, Colomer D, et al . Allogeneic stem-cell transplantation may overcome the adverse prognosis of unmutated VH gene in patients with chronic lymphocytic leukemia. J Clin Oncol , 2005, 23 (15): 3433-3438.
19.	顧衛軍, 徐衛, 錢思軒, 等. 利妥昔單克隆抗體聯合氟達拉濱及環磷酰胺治療慢性淋巴細胞白血病. 中國實驗血液學雜志, 2008, (04):938-942.
20.	王欣, 劉林, 陳建斌, 等. 氟達拉濱聯合環磷酰胺治療慢性淋巴細胞白血病的臨床研究. 重慶醫學, 2009, 38(10): 1210-1212.
21.	方成, 徐衛, 徐敏, 等. 氟達拉濱和環磷酰胺聯合利妥昔單抗治療慢性淋巴細胞白血病療效分析. 中華血液學雜志, 2011, 32(1): 3-7.

1. 2 Ricci F, Tedeschi A, Morra E, et al . Fludarabine in the treatment of chronic lymphocytic leukemia: a review. Ther Clin Risk Manag , 2009, 5(1): 187-207.
2. 3 Wierda W, O'Brien S, Faderl S, et al . A retrospective comparison of three sequential groups of patients with Recurrent/Refractory chronic lymphocytic leukemia treated with fludarabine-based regimens. Cancer , 2006, 106(2): 337-345.
3. 4 Hallek M, Fischer K, Fingerle-Rowson G, et al . Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial. Lancet , 2010, 376(9747): 1164-1174.
4. 5 Eichhorst BF, Busch R, Hopfinger G, et al . Fludarabine plus cyclophosphamide versus fludarabine alone in first-line therapy of younger patients with chronic lymphocytic leukemia. Blood , 2006, 107(3): 885-891.
5. 6 Grever MR, Lucas DM, Dewald GW, et al . Comprehensive assessment of genetic and molecular features predicting outcome in patients with chronic lymphocytic leukemia: results from the US Intergroup Phase III Trial E2997. Journal of Clinical Oncology , 2007, 25(7): 799-804.
6. 8 Robak T, Dmoszynska A, Solal-Celigny P, et al . Rituximab Plus Fludarabine and Cyclophosphamide Prolongs Progression-Free Survival Compared With Fludarabine and Cyclophosphamide Alone in Previously Treated Chronic Lymphocytic Leukemia. Journal of Clinical Oncology , 2010, 28(10): 1756-1765.
7. 9 Flinn IW, Neuberg DS, Grever MR, et al. Phase III trial of fludarabine plus cyclophosphamide compared with fludarabine for patients with previously untreated chronic lymphocytic leukemia: US Intergroup Trial E2997. Journal of Clinical Oncology , 2007, 25(7): 793-798.
8. 10 Dretzke J, Barton P, Kaambwa B, et al . Rituximab for the treatment of relapsed/refractory chronic lymphocytic leukaemia. Health Technol Assess , 2010, 14(Suppl. 2): 19-26.
9. 11 O'Brien S, Osterborg A. Ofatumumab: a new CD20 monoclonal antibody therapy for B-cell chronic lymphocytic leukemia. Clin Lymphoma Myeloma Leuk , 2010, 10(5): 361-368.
10. 12 Byrd JC, Kipps TJ, Flinn IW, et al . Phase 1/2 study of lumiliximab combined with fludarabine, cyclophosphamide, and rituximab in patients with relapsed or refractory chronic lymphocytic leukemia. Blood , 2010, 115(3): 489-495.
11. 13 Wierda W, O'Brien S, Wen S, et al . Chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab for relapsed and refractory chronic lymphocytic leukemia. J Clin Oncol , 2005, 23(18): 4070-4078.
12. 14 Casak SJ, Lemery SJ, Shen YL, et al . U.S. Food and drug administration approval: rituximab in combination with fludarabine and cyclophosphamide for the treatment of patients with chronic lymphocytic leukemia. Oncologist , 2011, 16(1): 97-104.
13. 16 Dohner H, Fischer K, Bentz M, et al . p53 gene deletion predicts for poor survival and non-response to therapy with purine analogs in chronic B-cell leukemias. Blood , 1995, 85 (6): 1580-1589.
14. 17 Grever MR, Lucas DM, Dewald GW, et al . Comprehensive assessment of genetic and molecular features predicting outcome in patients with chronic lymphocytic leukemia: results from the US Intergroup Phase III Trial E2997. J Clin Oncol , 2007, 25 (7): 799-804.
15. 18 Dohner H, Stilgenbauer S, James MR, et al . 11q deletions identify a new subset of B-cell chronic lymphocytic leukemia characterized by extensive nodal involvement and inferior prognosis. Blood , 1997, 89(7): 2516-2522.
16. 19 Tsimberidou AM, Tam C, Abruzzo LV, et al . Chemoimmunotherapy may overcome the adverse prognostic significance of 11q deletion in previously untreated patients with chronic lymphocytic leukemia. Cancer , 2009, 115(2): 373-380.
17. 20 Schlette EJ, Admirand J, Wierda W, et al . p53 expression by immunohistochemistry is an important determinant of survival in patients with chronic lymphocytic leukemia receiving frontline chemo-immunotherapy. Leuk Lymphoma , 2009, 50 (10): 1597-1605.
18. 21 Moreno C, Villamor N, Colomer D, et al . Allogeneic stem-cell transplantation may overcome the adverse prognosis of unmutated VH gene in patients with chronic lymphocytic leukemia. J Clin Oncol , 2005, 23 (15): 3433-3438.
19. 顧衛軍, 徐衛, 錢思軒, 等. 利妥昔單克隆抗體聯合氟達拉濱及環磷酰胺治療慢性淋巴細胞白血病. 中國實驗血液學雜志, 2008, (04):938-942.
20. 王欣, 劉林, 陳建斌, 等. 氟達拉濱聯合環磷酰胺治療慢性淋巴細胞白血病的臨床研究. 重慶醫學, 2009, 38(10): 1210-1212.
21. 方成, 徐衛, 徐敏, 等. 氟達拉濱和環磷酰胺聯合利妥昔單抗治療慢性淋巴細胞白血病療效分析. 中華血液學雜志, 2011, 32(1): 3-7.

《中國循證醫學雜志》

利妥昔單抗聯合FC方案治療慢性淋巴細胞白血病的療效和安全性系統評價

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《中國循證醫學雜志》

利妥昔單抗聯合FC方案治療慢性淋巴細胞白血病的療效和安全性系統評價

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