不同评分系统对初诊慢性髓系白血病患者临床疗效的预估价值
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摘要
目的:探讨4种评分系统对甲磺酸伊马替尼(IM)治疗初诊慢性髓系白血病慢性期(CML-CP)患者临床疗效的预估价值,以及与深层分子学反应(MR4.5)之间的相互关系。方法:回顾性分析我院2008年1月至2017年12月接受IM治疗的240例初诊CML-CP患者的临床资料,根据4种评分系统分别进行危险度分层,并分析4种评分系统与3个月早期分子学反应(3M-EMR)、6个月完全细胞遗传学反应(6M-CCyR)和12个月主要分子学反应(12M-MMR)之间的关系,以及4种评分系统与MR4.5之间的相关性。结果:240例患者治疗满3个月时,有219例患者评估EMR,其中有164例(74.9%)患者获得3M-EMR;治疗满6个月时,有180例患者评估CCyR,其中有130例(72.2%)患者获得6M-CCyR;治疗满12个月时,有111例患者评估MMR,其中有60例(54.1%)患者获得12M-MMR。4种评分系统的低危组患者(低危+中危)相比高危组患者对IM的治疗反应性更好,其中Sokal及ELTS评分与3M-EMR差异有统计学意义(P<0.05),EUTOS及ELTS评分与12M-MMR差异有统计学意义(P<0.05);多因素回归分析发现,Sokal评分(HR=0.69,95%CI:0.22-1.37,P=0.018)和3M-EMR(HR=0.47,95%CI:0.28-0.84,P<0.01)与MR4.5独立相关,Sokal评分与3M-EMR结合能更好地预测MR4.5(HR=0.42,95%CI:0.21-0.82,P<0.01)。结论:IM治疗初诊CML-CP患者的临床疗效显著,低危组患者比高危组治疗反应更佳。Sokal及ELTS评分能较好地评估3M-EMR,而EUTOS及ELTS评分能较好地评估12M-MMR;Sokal评分的低危组与3M-EMR结合能更好地预测MR4.5。本研究结果为CML患者临床疗效的预估和及时更改治疗方案提供了参考依据,对预测MR4.5也具有参考价值。
Objective: To explore the values of 4 prognostic score systems in evaluation of clinical effecacy for patients with newly diagnosed chronic myeloid leukemia in chronic phase(CML-CP) treated with imatnib mesylate(IM)and the relationship between 4 prognostic score systems and deep molecular response(MR4.5). Methods: The clinical data of 240 CML-CP patients treated with imatinib mesylate in our hospital between Janunay 2008 and December 2017 were analyzed retrospecively. The risk was stratified according to 4 prognostic score systems, the relationship between the 4 prognostic score systems and 3-month early molecular response(3 M-EMR), 6 month complete cytogenetic response(6 M-CCy R), 12-month major molecular response(12 M-MMR) as well as the correlation of the 4 prognostic score systems with deep molecalar response were analyzed. Results: At the end of treatment for 3 months, the EMR was evaluated for 219 patients, among them 164(74.9%) patients achieved 3 M-EMR; at the end of treatment for 6 months, CCyR was evaluated for 180 pathsents, among them 130(72.2%) patients achicved 6 M-CCyR; at the end of treatment for 12 months,the MMR was evaluated for 111 patients, among them 60(54.1%) patients achieved 12 M-MMR. Compared with the high-risk group, the treatment response to IM in the low-risk group(including the low-risk group and the intermediate-risk group) was better. There was significant difference in 3 M-EMR according to Sokal score and ELTS score(P<0.05), and there was significant difference in 12 M-MMR according to EUTOS score and ELTS score(P<0.05). Logistic regression analysis revealed Sokal score(HR=0.69, 95%CI:0.22-1.37, P<0.05) and 3 M-EMR(HR=0.47, 95%CI:0.28-0.84, P<0.01) independently related with MR4.5, The combination of Sokal score, especially the low risk with 3 M-EMR much more can predict MR4.5(HR=0.42, 95%CI=0.21-0.82, P<0.01). Conclusion: There is a remarkable clinical efficacy of imatinib mesylate on CML-CP patients, moreover, low risk group has a better therapeutic response. Both Sokal score and ELTS score evaluate 3 M-EMR better, both EUTOS score and ELTS score evaluate 12 M-MMR better. The combination of low risk in Sokal score with 3 M-EMR much more can predict MR4.5. The results of this study provide the reference basis for evaluating the clinical therapentic efficacy and timely modifying the therapeutic regimens for CML patients, also possess the reference value for predicting the MR4.5.
Objective: To explore the values of 4 prognostic score systems in evaluation of clinical effecacy for patients with newly diagnosed chronic myeloid leukemia in chronic phase(CML-CP) treated with imatnib mesylate(IM)and the relationship between 4 prognostic score systems and deep molecular response(MR4.5). Methods: The clinical data of 240 CML-CP patients treated with imatinib mesylate in our hospital between Janunay 2008 and December 2017 were analyzed retrospecively. The risk was stratified according to 4 prognostic score systems, the relationship between the 4 prognostic score systems and 3-month early molecular response(3 M-EMR), 6 month complete cytogenetic response(6 M-CCy R), 12-month major molecular response(12 M-MMR) as well as the correlation of the 4 prognostic score systems with deep molecalar response were analyzed. Results: At the end of treatment for 3 months, the EMR was evaluated for 219 patients, among them 164(74.9%) patients achieved 3 M-EMR; at the end of treatment for 6 months, CCyR was evaluated for 180 pathsents, among them 130(72.2%) patients achicved 6 M-CCyR; at the end of treatment for 12 months,the MMR was evaluated for 111 patients, among them 60(54.1%) patients achieved 12 M-MMR. Compared with the high-risk group, the treatment response to IM in the low-risk group(including the low-risk group and the intermediate-risk group) was better. There was significant difference in 3 M-EMR according to Sokal score and ELTS score(P<0.05), and there was significant difference in 12 M-MMR according to EUTOS score and ELTS score(P<0.05). Logistic regression analysis revealed Sokal score(HR=0.69, 95%CI:0.22-1.37, P<0.05) and 3 M-EMR(HR=0.47, 95%CI:0.28-0.84, P<0.01) independently related with MR4.5, The combination of Sokal score, especially the low risk with 3 M-EMR much more can predict MR4.5(HR=0.42, 95%CI=0.21-0.82, P<0.01). Conclusion: There is a remarkable clinical efficacy of imatinib mesylate on CML-CP patients, moreover, low risk group has a better therapeutic response. Both Sokal score and ELTS score evaluate 3 M-EMR better, both EUTOS score and ELTS score evaluate 12 M-MMR better. The combination of low risk in Sokal score with 3 M-EMR much more can predict MR4.5. The results of this study provide the reference basis for evaluating the clinical therapentic efficacy and timely modifying the therapeutic regimens for CML patients, also possess the reference value for predicting the MR4.5.
引文
1 Kantarjian H,O'Brien S,Jabbour E,et al.Improved survival in chronic myeloid leukemia since the introduction of imatinib therapy:a single-institution historical experience.Blood,2012;119(9):1981-1987.
2 Kalmanti L,Saussele S,Lauseker M,et al.Safety and efficacy of imatinib in CML over a period of 10 years:data from the randomized CML-study IV.Leukemia,2015;29(5):1123-1132.
3 Hehlmann R,Muller MC,Lauseker M,et al.Deep molecular response is reached by the majority of patients treated with imatinib,predicts survival,and is achieved more quickly by optimized highdose imatinib:results from the randomized CML-study IV.J Clin Oncol,2014;32(5):415-423.
4 Saussele S,Richter J,Hochhaus A,et al.The concept of treatmentfree remission in chronic myeloid leukemia.Leukemia,2016;30(8):1638-1647.
5 Baccarani M,Deininger MW,Rosti G,et al.European LeukemiaNet recommendations for the management of chronic myeloid leukemia:2013.Blood,2013;122(6):872-884.
6 Mauro MJ.Goals for chronic myeloid leukemia TK inhibitor treatment:how little disease is too much?Hematology Am Soc Hematol Educ Program,2014;2014(1):234-239.
7 Mahon FX.Discontinuation of tyrosine kinase therapy in CML.Ann Hematol,2015;94 Suppl 2:S187-193.
8 Jiang Q,Liu ZC,Zhang SX,et al.Young age and high cost are associated with future preference for stopping tyrosine kinase inhibitor therapy in Chinese with chronic myeloid leukemia.JCancer Res Clin Oncol,2016;142(7):1539-1547.
9中华医学会血液学分会.中国慢性髓系白血病诊断与治疗指南(2011年版)中华血液学杂志,2011;32(6):426-432.
10 Sokal JE,Cox EB,Baccarani M,et al.Prognostic discrimination in"good-risk"chronic granulocytic leukemia.Blood,1984;63(4):789-799.
11 Hasford J,Pfirrmann M,Hehlmann R,et al.A new prognostic score for survival of patients with chronic myeloid leukemia treated with interferon alfa.Writing Committee for the Collaborative CMLPrognostic Factors Project Group.J Natl Cancer Inst,1998;90(11):850-858.
12 Hasford J,Baccarani M,Hoffmann V,et al.Predicting complete cytogenetic response and subsequent progression-free survival in2060 patients with CML on imatinib treatment:the EUTOS score.Blood,2011;118(3):686-692.
13 Pfirrmann M,Baccarani M,Saussele S,et al.Prognosis of long-term survival considering disease-specific death in patients with chronic myeloid leukemia.Leukemia,2016;30(1):48-56.
14 Banjar HR,Alsobhi E.Consistency test between scoring systems for predicting outcomes of chronic myeloid leukemia in a Saudi population treated with imatinib.Int Sch Res Notices,2017;2017:1076493.
15 Jabbour E,Kantarjian HM,Saglio G,et al.Early response with dasatinib or imatinib in chronic myeloid leukemia:3-year follow-up from a randomized phase 3 trial(DASISION).Blood,2014;123(4):494-500.
16 Tao Z,Liu B,Zhao Y,et al.EUTOS score predicts survival and cytogenetic response in patients with chronic phase chronic myeloid leukemia treated with first-line imatinib.Leuk Res,2014;38(9):1030-1035.
17 Uz B,Buyukasik Y,Atay H,et al.EUTOS CML prognostic scoring system predicts ELN-based'event-free survival'better than Euro/Hasford and Sokal systems in CML patients receiving front-line imatinib mesylate.Hematology,2013;18(5):247-252.
18 Bonifacio M,Binotto G,Calistri E,et al.EUTOS score predicts early optimal response to imatinib according to the revised 2013ELN recommendations.Ann Hematol,2014;93(1):163-164.
19 Iriyama N,Hatta Y,Kobayashi S,et al.The European Treatment and Outcome Study score is associated with clinical outcomes and treatment response following European LeukemiaNet 2013recommendations in chronic-phase chronic myeloid leukemia.Int JHematol,2014;100(4):379-385.
20 Hughes TP,Hochhaus A,Branford S,et al.Long-term prognostic significance of early molecular response to imatinib in newly diagnosed chronic myeloid leukemia:an analysis from the International Randomized Study of Interferon and STI571(IRIS).Blood,2010;116(19):3758-3765.
21江倩,赵东陆,金洁,等.国产甲磺酸伊马替尼治疗慢性髓性白血病慢性期早期疗效和安全性的前瞻性、多中心临床研究.中华血液学杂志,2015;36(8):651-655.
22 Iliakis T,Papadopoulou V,Diamantopoulos PT,et al.Cessation of tyrosine kinase inhibitors in patients with chronic-phase chronic myelogenous leukemia following durable complete molecular response:a single center facing the dilemma.Anticancer Res,2013;33(8):3509-3514.
23 Cortes J,Quintas-Cardama A,Jones D,et al.Immune modulation of minimal residual disease in early chronic phase chronic myelogenous leukemia:a randomized trial of frontline high-dose imatinib mesylate with or without pegylated interferon alpha-2b and granulocyte-macrophage colony-stimulating factor.Cancer,2011;117(3):572-580.
24 Elsayed AG,Srivastava R,Jamil MO.Treatment-Free Remission:a New Therapeutic Goal in Chronic Myelogenous Leukemia.Curr Oncol Rep,2017;19(12):77.
25 Branford S,Yeung DT,Ross DM,et al.Early molecular response and female sex strongly predict stable undetectable BCR-ABL1,the criteria for imatinib discontinuation in patients with CML.Blood,2013;121(19):3818-3824.
26 Ko PS,Yu YB,Liu YC,et al.Moderate anemia at diagnosis is an independent prognostic marker of the EUTOS,Sokal,and Hasford scores for survival and treatment response in chronic-phase,chronic myeloid leukemia patients with frontline imatinib.Curr Med Res Opin,2017;33(10):1737-1744.
2 Kalmanti L,Saussele S,Lauseker M,et al.Safety and efficacy of imatinib in CML over a period of 10 years:data from the randomized CML-study IV.Leukemia,2015;29(5):1123-1132.
3 Hehlmann R,Muller MC,Lauseker M,et al.Deep molecular response is reached by the majority of patients treated with imatinib,predicts survival,and is achieved more quickly by optimized highdose imatinib:results from the randomized CML-study IV.J Clin Oncol,2014;32(5):415-423.
4 Saussele S,Richter J,Hochhaus A,et al.The concept of treatmentfree remission in chronic myeloid leukemia.Leukemia,2016;30(8):1638-1647.
5 Baccarani M,Deininger MW,Rosti G,et al.European LeukemiaNet recommendations for the management of chronic myeloid leukemia:2013.Blood,2013;122(6):872-884.
6 Mauro MJ.Goals for chronic myeloid leukemia TK inhibitor treatment:how little disease is too much?Hematology Am Soc Hematol Educ Program,2014;2014(1):234-239.
7 Mahon FX.Discontinuation of tyrosine kinase therapy in CML.Ann Hematol,2015;94 Suppl 2:S187-193.
8 Jiang Q,Liu ZC,Zhang SX,et al.Young age and high cost are associated with future preference for stopping tyrosine kinase inhibitor therapy in Chinese with chronic myeloid leukemia.JCancer Res Clin Oncol,2016;142(7):1539-1547.
9中华医学会血液学分会.中国慢性髓系白血病诊断与治疗指南(2011年版)中华血液学杂志,2011;32(6):426-432.
10 Sokal JE,Cox EB,Baccarani M,et al.Prognostic discrimination in"good-risk"chronic granulocytic leukemia.Blood,1984;63(4):789-799.
11 Hasford J,Pfirrmann M,Hehlmann R,et al.A new prognostic score for survival of patients with chronic myeloid leukemia treated with interferon alfa.Writing Committee for the Collaborative CMLPrognostic Factors Project Group.J Natl Cancer Inst,1998;90(11):850-858.
12 Hasford J,Baccarani M,Hoffmann V,et al.Predicting complete cytogenetic response and subsequent progression-free survival in2060 patients with CML on imatinib treatment:the EUTOS score.Blood,2011;118(3):686-692.
13 Pfirrmann M,Baccarani M,Saussele S,et al.Prognosis of long-term survival considering disease-specific death in patients with chronic myeloid leukemia.Leukemia,2016;30(1):48-56.
14 Banjar HR,Alsobhi E.Consistency test between scoring systems for predicting outcomes of chronic myeloid leukemia in a Saudi population treated with imatinib.Int Sch Res Notices,2017;2017:1076493.
15 Jabbour E,Kantarjian HM,Saglio G,et al.Early response with dasatinib or imatinib in chronic myeloid leukemia:3-year follow-up from a randomized phase 3 trial(DASISION).Blood,2014;123(4):494-500.
16 Tao Z,Liu B,Zhao Y,et al.EUTOS score predicts survival and cytogenetic response in patients with chronic phase chronic myeloid leukemia treated with first-line imatinib.Leuk Res,2014;38(9):1030-1035.
17 Uz B,Buyukasik Y,Atay H,et al.EUTOS CML prognostic scoring system predicts ELN-based'event-free survival'better than Euro/Hasford and Sokal systems in CML patients receiving front-line imatinib mesylate.Hematology,2013;18(5):247-252.
18 Bonifacio M,Binotto G,Calistri E,et al.EUTOS score predicts early optimal response to imatinib according to the revised 2013ELN recommendations.Ann Hematol,2014;93(1):163-164.
19 Iriyama N,Hatta Y,Kobayashi S,et al.The European Treatment and Outcome Study score is associated with clinical outcomes and treatment response following European LeukemiaNet 2013recommendations in chronic-phase chronic myeloid leukemia.Int JHematol,2014;100(4):379-385.
20 Hughes TP,Hochhaus A,Branford S,et al.Long-term prognostic significance of early molecular response to imatinib in newly diagnosed chronic myeloid leukemia:an analysis from the International Randomized Study of Interferon and STI571(IRIS).Blood,2010;116(19):3758-3765.
21江倩,赵东陆,金洁,等.国产甲磺酸伊马替尼治疗慢性髓性白血病慢性期早期疗效和安全性的前瞻性、多中心临床研究.中华血液学杂志,2015;36(8):651-655.
22 Iliakis T,Papadopoulou V,Diamantopoulos PT,et al.Cessation of tyrosine kinase inhibitors in patients with chronic-phase chronic myelogenous leukemia following durable complete molecular response:a single center facing the dilemma.Anticancer Res,2013;33(8):3509-3514.
23 Cortes J,Quintas-Cardama A,Jones D,et al.Immune modulation of minimal residual disease in early chronic phase chronic myelogenous leukemia:a randomized trial of frontline high-dose imatinib mesylate with or without pegylated interferon alpha-2b and granulocyte-macrophage colony-stimulating factor.Cancer,2011;117(3):572-580.
24 Elsayed AG,Srivastava R,Jamil MO.Treatment-Free Remission:a New Therapeutic Goal in Chronic Myelogenous Leukemia.Curr Oncol Rep,2017;19(12):77.
25 Branford S,Yeung DT,Ross DM,et al.Early molecular response and female sex strongly predict stable undetectable BCR-ABL1,the criteria for imatinib discontinuation in patients with CML.Blood,2013;121(19):3818-3824.
26 Ko PS,Yu YB,Liu YC,et al.Moderate anemia at diagnosis is an independent prognostic marker of the EUTOS,Sokal,and Hasford scores for survival and treatment response in chronic-phase,chronic myeloid leukemia patients with frontline imatinib.Curr Med Res Opin,2017;33(10):1737-1744.