Comparison of Mitoxantrone in Combination with Intermediate-dose Cytarabine versus High-dose Cytarabine as Consolidation Therapies for Young Non-APL Acute Myeloid Leukemia Patients with Favorable and Intermediate Cytogenetics
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摘要
In this study,we compared the efficacy of mitoxantrone in combination with intermediate-dose cytarabine(HAM) with that of high-dose cytarabine alone(Hi DAC) as consolidation regimens in non-acute promyelocytic leukemia(APL) acute myeloid leukemia patients with favorable and intermediate cytogenetics.A total of 62 patients from Shenzhen People's Hospital were enrolled in this study.All patients enrolled received standard induction chemotherapy and achieved the first complete remission(CR1).In these patients,24 received Hi DAC and 38 received HAM as consolidation.The median relapse free survival(RFS) and overall survival(OS) were similar between these two consolidation regimens.Even in subgroup analysis according to risk stratification,the combination regimen conferred no benefit in longterm outcome in patients with favorable or intermediate cytogenetics.However,in patients receiving HAM regimen,the lowest neutrophil count was lower,neutropenic period longer,neutropenic fever rate higher,and more platelet transfusion support was required.HAM group also tended to have higher rate of sepsis than Hi DAC group.According to our results,we suggest that combination treatment with mitoxantrone and intermediate-dose cytarabine has limited value as compared to Hi DAC,even in young non-APL AML patients with favorable and intermediate cytogenetics.
In this study,we compared the efficacy of mitoxantrone in combination with intermediate-dose cytarabine(HAM) with that of high-dose cytarabine alone(Hi DAC) as consolidation regimens in non-acute promyelocytic leukemia(APL) acute myeloid leukemia patients with favorable and intermediate cytogenetics.A total of 62 patients from Shenzhen People's Hospital were enrolled in this study.All patients enrolled received standard induction chemotherapy and achieved the first complete remission(CR1).In these patients,24 received Hi DAC and 38 received HAM as consolidation.The median relapse free survival(RFS) and overall survival(OS) were similar between these two consolidation regimens.Even in subgroup analysis according to risk stratification,the combination regimen conferred no benefit in longterm outcome in patients with favorable or intermediate cytogenetics.However,in patients receiving HAM regimen,the lowest neutrophil count was lower,neutropenic period longer,neutropenic fever rate higher,and more platelet transfusion support was required.HAM group also tended to have higher rate of sepsis than Hi DAC group.According to our results,we suggest that combination treatment with mitoxantrone and intermediate-dose cytarabine has limited value as compared to Hi DAC,even in young non-APL AML patients with favorable and intermediate cytogenetics.
In this study,we compared the efficacy of mitoxantrone in combination with intermediate-dose cytarabine(HAM) with that of high-dose cytarabine alone(Hi DAC) as consolidation regimens in non-acute promyelocytic leukemia(APL) acute myeloid leukemia patients with favorable and intermediate cytogenetics.A total of 62 patients from Shenzhen People's Hospital were enrolled in this study.All patients enrolled received standard induction chemotherapy and achieved the first complete remission(CR1).In these patients,24 received Hi DAC and 38 received HAM as consolidation.The median relapse free survival(RFS) and overall survival(OS) were similar between these two consolidation regimens.Even in subgroup analysis according to risk stratification,the combination regimen conferred no benefit in longterm outcome in patients with favorable or intermediate cytogenetics.However,in patients receiving HAM regimen,the lowest neutrophil count was lower,neutropenic period longer,neutropenic fever rate higher,and more platelet transfusion support was required.HAM group also tended to have higher rate of sepsis than Hi DAC group.According to our results,we suggest that combination treatment with mitoxantrone and intermediate-dose cytarabine has limited value as compared to Hi DAC,even in young non-APL AML patients with favorable and intermediate cytogenetics.
引文
1 Dombret H,Gardin C.An update of current treatments for adult acute myeloid leukemia.Blood,2016,127(1):53-61
2 Mayer RJ,Davis RB,Schiffer CA,et al.Intensive postremission chemotherapy in adults with acute myeloid leukemia.Cancer and Leukemia Group B.N Engl J Med,1994,331(14):896-903
3 Bloomfield CD,Lawrence D,Byrd JC,et al.Frequency of prolonged remission duration after highdose cytarabine intensification in acute myeloid leukemia varies by cytogenetic subtype.Cancer Res,1998,58(18):4173-4179
4 De Kouchkovsky I,Abdul-Hay M.Acute myeloid leukemia:a comprehensive review and 2016 update.Blood Cancer J,2016,6(7):e441
5 Lowenberg B.Sense and nonsense of high-dose cytarabine for acute myeloid leukemia.Blood,2013,121(1):26-28
6 Schaich M,R?llig C.Soucek S,et al.Cytarabine dose of 36 g/m2 compared with 12 g/m2 within first consolidation in acute myeloid leukemia:results of patients enrolled onto the prospective randomized AML96 study.J Clin Oncol,2011,29(19):2696-2702
7 Lowenberg B,Pabst T,vellenga E,et al.Cytarabine dose for acute myeloid leukemia.N Engl J Med,2011,364(11):1027-1036
8 Mandelli F,Vignetti M,Suciu S,et al.Daunorubicin versus mitoxantrone versus idarubicin as induction and consolidation chemotherapy for adults with acute myeloid leukemia:the EORTC and GIMEMA Groups Study AML-10.J Clin Oncol,2009,27(32):5397-5403
9 Larson SM,Campbell NP,Huo D,et al.High dose cytarabine and mitoxantrone:an effective induction regimen for high-risk acute myeloid leukemia(AML).Leuk Lymphoma,2012,53(3):445-450
10 Schlenk RF,Germing U,Hartmann F,et al.Highdose cytarabine and mitoxantrone in consolidation therapy for acute promyelocytic leukemia.Leukemia,2005,19(6):978-983
11 Trifilio SM,Rademaker AW,Newman D,et al.Mitoxantrone and etoposide with or without intermediate dose cytarabine for the treatment of primary induction failure or relapsed acute myeloid leukemia.Leuk Res,2012,36(4):394-396
12 O’Donnell MR,Tallman MS,Abboud CN,et al.Acute myeloid leukemia,version 2.2013.J Natl Compr Canc Netw,2013,11(9):1047-1055
13 Cheson BD,Bennett JM,Kopecky KJ,et al.Revised recommendations of the International Working Group for Diagnosis,Standardization of Response Criteria,Treatment Outcomes,and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia.J Clin Oncol,2003,21(24):4642-4649
14 Miyawaki S,Ohtake S,Fujisawa S,et al.A randomized comparison of 4 courses of standard-dose multiagent chemotherapy versus 3 courses of high-dose cytarabine alone in postremission therapy for acute myeloid leukemia in adults:the JALSG AML201Study.Blood,2011,117(8):2366-2372
15 Thomas X,Elhamri M,Raffoux E,et al,Comparison of high-dose cytarabine and timed-sequential chemotherapy as consolidation for younger adults with AML in first remission:the ALFA-9802 study.Blood,2011,118(7):1754-1762
16 Schaich M,Parmentier S,Kramer M,et al.High-dose cytarabine consolidation with or without additional amsacrine and mitoxantrone in acute myeloid leukemia:results of the prospective randomized AML2003trial.J Clin Oncol,2013,31(17):2094-2102
17 Fazlina N,Maha A,Jamal R,et al,Expression of multidrug resistance(MDR)proteins and in vitro drug resistance in acute leukemias.Hematology,2007,12(1):33-37
18 Zhang W,Ding Y,Wu H,et al,Retrospective comparison of fludarabine in combination with intermediate-dose cytarabine versus high-dose cytarabine as consolidation therapies for acute myeloid leukemia.Medicine(Baltimore),2014,93(27):e134
2 Mayer RJ,Davis RB,Schiffer CA,et al.Intensive postremission chemotherapy in adults with acute myeloid leukemia.Cancer and Leukemia Group B.N Engl J Med,1994,331(14):896-903
3 Bloomfield CD,Lawrence D,Byrd JC,et al.Frequency of prolonged remission duration after highdose cytarabine intensification in acute myeloid leukemia varies by cytogenetic subtype.Cancer Res,1998,58(18):4173-4179
4 De Kouchkovsky I,Abdul-Hay M.Acute myeloid leukemia:a comprehensive review and 2016 update.Blood Cancer J,2016,6(7):e441
5 Lowenberg B.Sense and nonsense of high-dose cytarabine for acute myeloid leukemia.Blood,2013,121(1):26-28
6 Schaich M,R?llig C.Soucek S,et al.Cytarabine dose of 36 g/m2 compared with 12 g/m2 within first consolidation in acute myeloid leukemia:results of patients enrolled onto the prospective randomized AML96 study.J Clin Oncol,2011,29(19):2696-2702
7 Lowenberg B,Pabst T,vellenga E,et al.Cytarabine dose for acute myeloid leukemia.N Engl J Med,2011,364(11):1027-1036
8 Mandelli F,Vignetti M,Suciu S,et al.Daunorubicin versus mitoxantrone versus idarubicin as induction and consolidation chemotherapy for adults with acute myeloid leukemia:the EORTC and GIMEMA Groups Study AML-10.J Clin Oncol,2009,27(32):5397-5403
9 Larson SM,Campbell NP,Huo D,et al.High dose cytarabine and mitoxantrone:an effective induction regimen for high-risk acute myeloid leukemia(AML).Leuk Lymphoma,2012,53(3):445-450
10 Schlenk RF,Germing U,Hartmann F,et al.Highdose cytarabine and mitoxantrone in consolidation therapy for acute promyelocytic leukemia.Leukemia,2005,19(6):978-983
11 Trifilio SM,Rademaker AW,Newman D,et al.Mitoxantrone and etoposide with or without intermediate dose cytarabine for the treatment of primary induction failure or relapsed acute myeloid leukemia.Leuk Res,2012,36(4):394-396
12 O’Donnell MR,Tallman MS,Abboud CN,et al.Acute myeloid leukemia,version 2.2013.J Natl Compr Canc Netw,2013,11(9):1047-1055
13 Cheson BD,Bennett JM,Kopecky KJ,et al.Revised recommendations of the International Working Group for Diagnosis,Standardization of Response Criteria,Treatment Outcomes,and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia.J Clin Oncol,2003,21(24):4642-4649
14 Miyawaki S,Ohtake S,Fujisawa S,et al.A randomized comparison of 4 courses of standard-dose multiagent chemotherapy versus 3 courses of high-dose cytarabine alone in postremission therapy for acute myeloid leukemia in adults:the JALSG AML201Study.Blood,2011,117(8):2366-2372
15 Thomas X,Elhamri M,Raffoux E,et al,Comparison of high-dose cytarabine and timed-sequential chemotherapy as consolidation for younger adults with AML in first remission:the ALFA-9802 study.Blood,2011,118(7):1754-1762
16 Schaich M,Parmentier S,Kramer M,et al.High-dose cytarabine consolidation with or without additional amsacrine and mitoxantrone in acute myeloid leukemia:results of the prospective randomized AML2003trial.J Clin Oncol,2013,31(17):2094-2102
17 Fazlina N,Maha A,Jamal R,et al,Expression of multidrug resistance(MDR)proteins and in vitro drug resistance in acute leukemias.Hematology,2007,12(1):33-37
18 Zhang W,Ding Y,Wu H,et al,Retrospective comparison of fludarabine in combination with intermediate-dose cytarabine versus high-dose cytarabine as consolidation therapies for acute myeloid leukemia.Medicine(Baltimore),2014,93(27):e134