大剂量化疗后自体干细胞移植一线治疗滤泡性淋巴瘤的Meta分析
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摘要
目的
系统评价大剂量化疗后自体干细胞移植一线治疗滤泡性淋巴瘤的临床疗效与安全性。
方法
计算机检索MEDLINE数据库(1990-2009)、EMBASE数据库(1990-2009)、OVID数据库(1990-2009)、Cochrane图书馆(2009年第2期),手工检索美国血液年会(ASH)会议记录及相关文献的参考文献,评价纳入研究的方法学质量,采用STATA10.0软件和RevMan4.3软件进行统计分析。
结果
共纳入4个随机对照试验,包括941例患者。Meta分析的结果显示,大剂量化疗后自体干细胞移植一线治疗滤泡性淋巴瘤与常规化疗相比,总生存率HR0.82,95%CI[0.49,1.15]；无事件生存率HR 0.35,95%CI[0.24,0.47]；总缓解率RR 0.35,95%CI[0.96,1.30]；继发恶性肿瘤发生率RR 1.68,95%CI[0.47,6.07]。
结论
现有证据表明,大剂量化疗后自体干细胞移植一线治疗滤泡性淋巴瘤与常规化疗相比,不改善患者的总生存率及总缓解率,但能提高无事件生存率,不增加继发恶性肿瘤发生的风险。本研究纳入的病例数较少,结论尚需高质量多中心大样本随机对照试验证实。
Objective
To assess the effectiveness and safety of high-dose chemotherapy following autologous stem cell transplantation in first-line treatment of follicular lymphoma.
Methods
Randomized controlled trials (RCTs) of high-dose chemotherapy following autologous stem cell transplantation in first-line treatment of follicular lymphoma were collected from MEDLINE database(1990-2009),EMBASE database (1990-2009), OVID database (1990-2009), and the Cochrane Library(Issue2,2009). Meeting reports of ASH were hand searched. The methodological quality of included studies was evaluated, and data analyses were performed using software STATA 10.0 and Revman 4.3.
Results
A total of 4 RCTs involving 941 patients were included. The results of meta-analyses showed that HR of overall survival is 0.82,95%CI[0.49,1.15]; HR of event free survival is 0.35,95%CI[0.24,0.47]; RR of total remission rate is 0.35, 95%CI[0.96,1.30];RR of secondary cancers incidence rate is 1.68,95%CI[0.47,6.07].
Conclusions
According to the present evidence, high-dose chemotherapy following autologous stem cell transplantation can not improve overall survival and total remission rate, but can improve event free survival, and do not increase the secondary cancers incidence rate. However, more high-quality, multiple-center, large-sample randomized controlled trials are required.
系统评价大剂量化疗后自体干细胞移植一线治疗滤泡性淋巴瘤的临床疗效与安全性。
方法
计算机检索MEDLINE数据库(1990-2009)、EMBASE数据库(1990-2009)、OVID数据库(1990-2009)、Cochrane图书馆(2009年第2期),手工检索美国血液年会(ASH)会议记录及相关文献的参考文献,评价纳入研究的方法学质量,采用STATA10.0软件和RevMan4.3软件进行统计分析。
结果
共纳入4个随机对照试验,包括941例患者。Meta分析的结果显示,大剂量化疗后自体干细胞移植一线治疗滤泡性淋巴瘤与常规化疗相比,总生存率HR0.82,95%CI[0.49,1.15]；无事件生存率HR 0.35,95%CI[0.24,0.47]；总缓解率RR 0.35,95%CI[0.96,1.30]；继发恶性肿瘤发生率RR 1.68,95%CI[0.47,6.07]。
结论
现有证据表明,大剂量化疗后自体干细胞移植一线治疗滤泡性淋巴瘤与常规化疗相比,不改善患者的总生存率及总缓解率,但能提高无事件生存率,不增加继发恶性肿瘤发生的风险。本研究纳入的病例数较少,结论尚需高质量多中心大样本随机对照试验证实。
Objective
To assess the effectiveness and safety of high-dose chemotherapy following autologous stem cell transplantation in first-line treatment of follicular lymphoma.
Methods
Randomized controlled trials (RCTs) of high-dose chemotherapy following autologous stem cell transplantation in first-line treatment of follicular lymphoma were collected from MEDLINE database(1990-2009),EMBASE database (1990-2009), OVID database (1990-2009), and the Cochrane Library(Issue2,2009). Meeting reports of ASH were hand searched. The methodological quality of included studies was evaluated, and data analyses were performed using software STATA 10.0 and Revman 4.3.
Results
A total of 4 RCTs involving 941 patients were included. The results of meta-analyses showed that HR of overall survival is 0.82,95%CI[0.49,1.15]; HR of event free survival is 0.35,95%CI[0.24,0.47]; RR of total remission rate is 0.35, 95%CI[0.96,1.30];RR of secondary cancers incidence rate is 1.68,95%CI[0.47,6.07].
Conclusions
According to the present evidence, high-dose chemotherapy following autologous stem cell transplantation can not improve overall survival and total remission rate, but can improve event free survival, and do not increase the secondary cancers incidence rate. However, more high-quality, multiple-center, large-sample randomized controlled trials are required.
引文
1 Colombat P, Donadio D, Fouillard L, et al. Value of autologous bone marrow transplantation in follicular lymphoma:a France autogreffe retrospective study of 42 patients. Bone Marrow Transplant.1994,13:157-162.
2 Brice P, Simon D, Bouabdallah R, et al. High-dose therapy with autologous stem-cell transplantation (ASCT) after first progression prolonged survival of follicular lymphoma patients included in the prospective GELF 86 protocol.Ann Oncol.2000,11:1585-1590.
3 Rohatiner AZ, Johnson PW, Price CG, et al. Myeloablative therapy with autologous bone marrow transplantation as consolidation therapy for recurrent follicular lymphoma. J Clin Oncol.1994,12:1177-1184.
4 Rohatiner AZ, Nadler L, Davies AJ, et al. Myeloablative therapy with autologous bone marrow transplantation for follicular lymphoma at the time of second or subsequent remission: long-term follow-up. J Clin Oncol.2007,25:2554-2559.
5 Parmar MK, Torri V, Stewart L. Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints. Stat Med,1998; 17:2815-2834.
6 王静,莫传伟,陈群,等.应用Stata软件的Meta分析完成医学科研定量评价.中华中医药学刊,2008,5(26)：947-949.
7 Catherine Sebban, Nicolas Mounier, Nicole Brousse, et al.Standard chemotherapy with interferon compared with CHOP followed by high-dose therapy with autologous stem cell transplantation in untreated patients with advanced follicular lymphoma:the GELF-94 randomized study from the Groupe d'Etude des Lymphomes de l'Adulte (GELA).Blood.2006; 108:2540-2544.
8 Eric Deconinck, Charles Foussard, Noel Milpied, et al. High-dose therapy followed by autologous purged stem-cell transplantation and doxorubicin-based chemotherapy in patients with advanced follicular lymphoma:a randomized multicenter study by GOELAMS.Blood. 2005; 105:3817-3823.
9 Georg Lenz, Martin Dreyling, Eva Schiegnitz, et al. Myeloablative radiochemotherapy followed by autologous stem cell transplantation in first remission prolongs progression-free survival in follicular lymphoma:results of a prospective, randomized trial of the German Low-Grade Lymphoma Study Group. Blood.2004; 104:2667-2674.
10 Marco Ladetto, Federica De Marco, Fabio Benedetti, et al. Prospective, multicenter randomized GITMO/ⅡL trial comparing intensive (R-HDS) versus conventional (CHOP-R) chemoimmunotherapy in high-risk follicular lymphoma at diagnosis:the superior disease control of R-HDS does not translate into an overall survival advantage. Blood.2008; 111: 4004-4013.
1 郑声琴,何杰.滤泡性淋巴瘤病理诊断、治疗与预后的现状.东南大学学报(医学版),2006,25(6)：467-470.
2 Winter JN, Gascoyne RD, Besien KV.Proceeding:Low-Grade Lymphoma. Hematology 2004 San Diego, USA.American Society of Hematology 46th Annual Meeting,2004:203-220.
3 Tse WW, Lazarus HM, Van besien K.Stem cell transplantation in follicular lymphoma: progress at last?Bone Marrow Transplant,2004,34(11):929-938.
4 张桂新,冯四洲.造血干细胞移植治疗滤泡性淋巴瘤的研究进展.国际输血及血液学杂志,2007,30(2)：137-140.
5 Arcaini L, Montanari F, Alessandrino EP, et al. Immunochemotherapy with in vivo purging and autotransplant induces long clinical and molecular remission in advanced relapsed and refractory follicular lymphoma.Ann Oncol,2008,19(7):1331-1335.
6 Pham RN, Goolev TA, Keenev GE, et al.The impact of histologic grade on the outcome of high-dose therapy and autologous stem cell transplantion for follicular lymphoma.Bone Marrow Transplant,2007,40(11):1039-1044.
7 Brice P, Simon D, Bouabdallah R, et al. High-dose therapy with autologous stem-cell transplantation (ASCT) after first progression prolonged survival of follicular lymphoma patients included in the prospective GELF 86 protocol.Annals of Oncology,2000,11: 1585-1590.
8 Ganguly S, Divine CL, Deauna-Limayo D, et al. Autologous transplantation in patients with relapsed or high-grade follicular lymphoma provides long term disease-free survival and best median duration of response.Ann Hematol,2005,84(8):526-531.
9 Schouten HC, Qian W, Kvaloy S, et al. High-dose therapy improves progression-free survival and survival in relapsed follicular non-Hodgkin's lymphoma:results from the randomized European CUP trial.J Clin Oncol,2003,21(21):3918-3927.
10 Garvin AJ, Simon RM, Osborne CK, et al. An autopsy study of histologic progression in non-Hodgkin's lymphomas,192 cases from the National Cancer Institute. Cancer,1983,52: 393-398.
11 Hubbard SM, Chabner BA, DeVita VT Jr, et al. Histologic progression in non-Hodgkin's lymphoma. Blood,1982,59:258-264.
12 Bastion Y, Sebban C, Berger F, et al. Incidence, predictive factors, and outcome of lymphoma transformation in follicular lymphoma patients. J Clin Oncol,1997,15:1587-1594.
13 Yuen AR, Kamel OW, Halpern J, et al. Long-term survival after histologic transformation of low-grade follicular lymphoma. J Clin Oncol 1995,13:1726-1733.
14 Lerner RE, Burns LJ.Transformed lymphoma:an Achilles'heel of non-Hodgkin's lymphoma. Bone Marrow Transplant,2003,31:531-537.
15 Risdall R, Hoppe RT, Warnke R. Non-Hodgkin's lymphoma:a study of the evolution of the disease based upon 92 autopsied cases. Cancer,1979,44:529-542.
16 Acker B, Hoppe RT, Colby TV, et al. Histologic conversion in the non-Hodgkin's lymphomas. J Clin Oncol,1983,1:11-16.
17 Cullen MH, Lister TA, Brearley RI, et al. Histological transformation of non-Hodgkin's lymphoma:a prospective study.Cancer,1979,44:645-651.
18 Mehdi Hamadani, Don Benson M Jr, Thomas S Lin, et al. High-dose therapy and autologous stem cell transplantation for follicular lymphoma undergoing transformation to diffuse large B-cell lymphoma. European Journal of Haematology,2009,81:425-431.
19 Andreadis C, Schuster SJ, Chong EA, et al.Long-term event-free survivors after high-dose therapy and autologous stem-cell transplantation for low-grade follicular lymphoma.Bone Marrow Transplant,2005,36(11):955-961.
20 Eric Deconinck, Charles Foussard, Noel Milpied, et al. High-dose therapy followed by autologous purged stem-cell transplantation and
21 doxorubicin-based chemotherapy in patients with advanced follicular lymphoma:a randomized multicenter study by GOELAMS. Blood,2005;105:3817-3823.
22 Marco Ladetto, Federica De Marco, Fabio Benedetti, et al. Prospective, multicenter randomized GITMO/ⅡL trial comparing intensive (R-HDS) versus conventional (CHOP-R) chemoimmunotherapy in high-risk follicular lymphoma at diagnosis:the superior disease control of R-HDS does not translate into an overall survival advantage.Blood.2008,111: 4004-4013.
2 Brice P, Simon D, Bouabdallah R, et al. High-dose therapy with autologous stem-cell transplantation (ASCT) after first progression prolonged survival of follicular lymphoma patients included in the prospective GELF 86 protocol.Ann Oncol.2000,11:1585-1590.
3 Rohatiner AZ, Johnson PW, Price CG, et al. Myeloablative therapy with autologous bone marrow transplantation as consolidation therapy for recurrent follicular lymphoma. J Clin Oncol.1994,12:1177-1184.
4 Rohatiner AZ, Nadler L, Davies AJ, et al. Myeloablative therapy with autologous bone marrow transplantation for follicular lymphoma at the time of second or subsequent remission: long-term follow-up. J Clin Oncol.2007,25:2554-2559.
5 Parmar MK, Torri V, Stewart L. Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints. Stat Med,1998; 17:2815-2834.
6 王静,莫传伟,陈群,等.应用Stata软件的Meta分析完成医学科研定量评价.中华中医药学刊,2008,5(26)：947-949.
7 Catherine Sebban, Nicolas Mounier, Nicole Brousse, et al.Standard chemotherapy with interferon compared with CHOP followed by high-dose therapy with autologous stem cell transplantation in untreated patients with advanced follicular lymphoma:the GELF-94 randomized study from the Groupe d'Etude des Lymphomes de l'Adulte (GELA).Blood.2006; 108:2540-2544.
8 Eric Deconinck, Charles Foussard, Noel Milpied, et al. High-dose therapy followed by autologous purged stem-cell transplantation and doxorubicin-based chemotherapy in patients with advanced follicular lymphoma:a randomized multicenter study by GOELAMS.Blood. 2005; 105:3817-3823.
9 Georg Lenz, Martin Dreyling, Eva Schiegnitz, et al. Myeloablative radiochemotherapy followed by autologous stem cell transplantation in first remission prolongs progression-free survival in follicular lymphoma:results of a prospective, randomized trial of the German Low-Grade Lymphoma Study Group. Blood.2004; 104:2667-2674.
10 Marco Ladetto, Federica De Marco, Fabio Benedetti, et al. Prospective, multicenter randomized GITMO/ⅡL trial comparing intensive (R-HDS) versus conventional (CHOP-R) chemoimmunotherapy in high-risk follicular lymphoma at diagnosis:the superior disease control of R-HDS does not translate into an overall survival advantage. Blood.2008; 111: 4004-4013.
1 郑声琴,何杰.滤泡性淋巴瘤病理诊断、治疗与预后的现状.东南大学学报(医学版),2006,25(6)：467-470.
2 Winter JN, Gascoyne RD, Besien KV.Proceeding:Low-Grade Lymphoma. Hematology 2004 San Diego, USA.American Society of Hematology 46th Annual Meeting,2004:203-220.
3 Tse WW, Lazarus HM, Van besien K.Stem cell transplantation in follicular lymphoma: progress at last?Bone Marrow Transplant,2004,34(11):929-938.
4 张桂新,冯四洲.造血干细胞移植治疗滤泡性淋巴瘤的研究进展.国际输血及血液学杂志,2007,30(2)：137-140.
5 Arcaini L, Montanari F, Alessandrino EP, et al. Immunochemotherapy with in vivo purging and autotransplant induces long clinical and molecular remission in advanced relapsed and refractory follicular lymphoma.Ann Oncol,2008,19(7):1331-1335.
6 Pham RN, Goolev TA, Keenev GE, et al.The impact of histologic grade on the outcome of high-dose therapy and autologous stem cell transplantion for follicular lymphoma.Bone Marrow Transplant,2007,40(11):1039-1044.
7 Brice P, Simon D, Bouabdallah R, et al. High-dose therapy with autologous stem-cell transplantation (ASCT) after first progression prolonged survival of follicular lymphoma patients included in the prospective GELF 86 protocol.Annals of Oncology,2000,11: 1585-1590.
8 Ganguly S, Divine CL, Deauna-Limayo D, et al. Autologous transplantation in patients with relapsed or high-grade follicular lymphoma provides long term disease-free survival and best median duration of response.Ann Hematol,2005,84(8):526-531.
9 Schouten HC, Qian W, Kvaloy S, et al. High-dose therapy improves progression-free survival and survival in relapsed follicular non-Hodgkin's lymphoma:results from the randomized European CUP trial.J Clin Oncol,2003,21(21):3918-3927.
10 Garvin AJ, Simon RM, Osborne CK, et al. An autopsy study of histologic progression in non-Hodgkin's lymphomas,192 cases from the National Cancer Institute. Cancer,1983,52: 393-398.
11 Hubbard SM, Chabner BA, DeVita VT Jr, et al. Histologic progression in non-Hodgkin's lymphoma. Blood,1982,59:258-264.
12 Bastion Y, Sebban C, Berger F, et al. Incidence, predictive factors, and outcome of lymphoma transformation in follicular lymphoma patients. J Clin Oncol,1997,15:1587-1594.
13 Yuen AR, Kamel OW, Halpern J, et al. Long-term survival after histologic transformation of low-grade follicular lymphoma. J Clin Oncol 1995,13:1726-1733.
14 Lerner RE, Burns LJ.Transformed lymphoma:an Achilles'heel of non-Hodgkin's lymphoma. Bone Marrow Transplant,2003,31:531-537.
15 Risdall R, Hoppe RT, Warnke R. Non-Hodgkin's lymphoma:a study of the evolution of the disease based upon 92 autopsied cases. Cancer,1979,44:529-542.
16 Acker B, Hoppe RT, Colby TV, et al. Histologic conversion in the non-Hodgkin's lymphomas. J Clin Oncol,1983,1:11-16.
17 Cullen MH, Lister TA, Brearley RI, et al. Histological transformation of non-Hodgkin's lymphoma:a prospective study.Cancer,1979,44:645-651.
18 Mehdi Hamadani, Don Benson M Jr, Thomas S Lin, et al. High-dose therapy and autologous stem cell transplantation for follicular lymphoma undergoing transformation to diffuse large B-cell lymphoma. European Journal of Haematology,2009,81:425-431.
19 Andreadis C, Schuster SJ, Chong EA, et al.Long-term event-free survivors after high-dose therapy and autologous stem-cell transplantation for low-grade follicular lymphoma.Bone Marrow Transplant,2005,36(11):955-961.
20 Eric Deconinck, Charles Foussard, Noel Milpied, et al. High-dose therapy followed by autologous purged stem-cell transplantation and
21 doxorubicin-based chemotherapy in patients with advanced follicular lymphoma:a randomized multicenter study by GOELAMS. Blood,2005;105:3817-3823.
22 Marco Ladetto, Federica De Marco, Fabio Benedetti, et al. Prospective, multicenter randomized GITMO/ⅡL trial comparing intensive (R-HDS) versus conventional (CHOP-R) chemoimmunotherapy in high-risk follicular lymphoma at diagnosis:the superior disease control of R-HDS does not translate into an overall survival advantage.Blood.2008,111: 4004-4013.