同胞异基因造血干细胞移植治疗急性髓细胞白血病121例临床分析
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摘要
目的分析急性髓细胞白血病患者接受同胞全相合异基因造血干细胞移植的疗效。方法回顾性分析2008年1月至2017年12月在该院接受同胞异基因造血干细胞移植的121例急性髓细胞白血病患者的临床资料。采用白消安+环磷酰胺(BU/CY)、改良BU/CY+阿糖胞苷或去甲氧柔红霉素+BU/CY预处理方案,移植物抗宿主病治疗方案采用环孢素+甲氨蝶呤+吗替麦考酚酯,所有患者输注外周血干细胞或骨髓联合外周血干细胞。结果 121例患者中120例植入,中性粒细胞植入中位时间为11d,血小板植入中位时间为14d。Ⅱ～Ⅳ度急性移植物抗宿主病发生率为8.3%,慢性移植物抗宿主病发生率为23.0%。3年复发率为24.0%,移植前缓解组和未缓解组移植后复发率分别为15.9%和51.8%,移植前未缓解组复发率明显高于移植前缓解组(P<0.01)。所有患者3年预期总生存率和无病生存率分别为63.0%±3.4%和62.0%±1.8%,移植前缓解组和未缓解组患者3年预期总生存率为72.3%±13.1%和33.3%±11.4%,3年预期无病生存率分别为71.3%±10.7%和29.6%±3.3%;无论总生存率还是无病生存率,移植前缓解组均高于未缓解组(P<0.01)。结论同胞异基因造血干细胞移植是治疗急性髓细胞白血病的一种有效方法,应尽量争取在白血病缓解期行异基因造血干细胞移植。
Objective To analyze the efficacy of siblings totally compatible allogeneic hematopoietic stem cell transplantation(Allo-HSCT)for treating acute myelogenous leukemia.Methods The clinical data in 121 cases of acute myelogenous leukemia in this hospital from January 2008 to December 2017 receiving siblings Allo-HSCT were retrospectively analyzed.The preprocessing regimens including busulfan+cyclophosphamide(BU/CY),modified BU/CY+cytarabine or idarubicin+BU/CY were adopted.The graft-versus-host disease scheme adopted cyclosporine+ methotrexate+ mycophenolate mofetil.All patients received transfusion of peripheral blood stem cells(PBSC)or bone marrow combined PBSC.Results Among 121 cases,there were 120 cases of engraftment.The median time of neutrophil engraftment and platelet engraftment were 11 d and 14 drespectively.The incidence rate of gradeⅡ-Ⅳ acute graft versus host disease was 8.3%.The incidence rate of chronic graft versus host disease was 23.0%.The 3-year relapse rate was 24.0%.The relapse incidence rates in the patients with complete remission and non-complete remission before transplantation were15.9%and 51.8% respectively.The relapse incidence rate in the complete remission group was higher than that in the non-complete remission group(P<0.01).The 3-year estimated overall survival(OS)rate and disease-free survival(DFS)rate were 63.0%±3.4%and 62.0%±1.8%respectively.The 3-year estimated over survival rates before transplantation were 72.3% ±13.1% and 33.3% ±11.4%in the complete remission group and non-complete remission group respectively.The 3-year estimated disease-free survival rates were71.3%±10.7%and 29.6%±3.3%.The OS and DFS before transplantation in the complete remission group were higher than those in the non-complete remission group(P<0.01).Conclusion Siblings Allo-HSCT is an effective method for treating acute myelogenous leukemia.Try to conduct Allo-HSCT in leukemia remission stage.
Objective To analyze the efficacy of siblings totally compatible allogeneic hematopoietic stem cell transplantation(Allo-HSCT)for treating acute myelogenous leukemia.Methods The clinical data in 121 cases of acute myelogenous leukemia in this hospital from January 2008 to December 2017 receiving siblings Allo-HSCT were retrospectively analyzed.The preprocessing regimens including busulfan+cyclophosphamide(BU/CY),modified BU/CY+cytarabine or idarubicin+BU/CY were adopted.The graft-versus-host disease scheme adopted cyclosporine+ methotrexate+ mycophenolate mofetil.All patients received transfusion of peripheral blood stem cells(PBSC)or bone marrow combined PBSC.Results Among 121 cases,there were 120 cases of engraftment.The median time of neutrophil engraftment and platelet engraftment were 11 d and 14 drespectively.The incidence rate of gradeⅡ-Ⅳ acute graft versus host disease was 8.3%.The incidence rate of chronic graft versus host disease was 23.0%.The 3-year relapse rate was 24.0%.The relapse incidence rates in the patients with complete remission and non-complete remission before transplantation were15.9%and 51.8% respectively.The relapse incidence rate in the complete remission group was higher than that in the non-complete remission group(P<0.01).The 3-year estimated overall survival(OS)rate and disease-free survival(DFS)rate were 63.0%±3.4%and 62.0%±1.8%respectively.The 3-year estimated over survival rates before transplantation were 72.3% ±13.1% and 33.3% ±11.4%in the complete remission group and non-complete remission group respectively.The 3-year estimated disease-free survival rates were71.3%±10.7%and 29.6%±3.3%.The OS and DFS before transplantation in the complete remission group were higher than those in the non-complete remission group(P<0.01).Conclusion Siblings Allo-HSCT is an effective method for treating acute myelogenous leukemia.Try to conduct Allo-HSCT in leukemia remission stage.
引文
[1]中华医学会血液学分会白血病淋巴瘤学组.成人急性髓系白血病(非急性早幼粒细胞白血病)中国诊疗指南(2017年版)[J].中华血液学杂志,2017,38(3):177-182.
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[5] GIOVANNA L,MYRIAM L,ERIC B,et al.impact of conditioning regimen on outcomes for children with acute myeloid leukemia undergoing transplantation in first complete remission.An analysis on behalf of the pediatric disease working party of the European group for blood and marrow transplantation[J].Biol Blood Marrow Transplant,2017(23):467-474.
[6] LAI Y,MA J,SCHWARZENBERGER P,et al.Combination of CsA,MTX and low-dose,short-course mycophenolate mofetil for GVHD prophylaxis[J].Bone Marrow Transplant,2009,43(1):61-67.
[7] FIONAL D,ANDREW C,PERSIS A,et al.Diagnosis and management of acute graft-versus-host disease[J].Br J Haematol,2012,158(1):30-45.
[8] MADANH J,HILDEGARD T G,MUKTA A,et al.National institutes of health consensus development project on criteria for clinical trials in chronic graft-versus-host disease:I.the 2014diagnosis and staging working group report[J].Biol Blood Marrow Transplant,2015,21(3):389-401.
[9] SHIMONI A,LABOPIN M,SAVANI B,et al.Long-term survival and late events after allogeneic stem cell transplantation from HLA-matched siblings for acute myeloid leukemia with myeloablative compared to reduced-intensity conditioning:a report on behalf of the acute leukemia working party of European group for blood and marrow transplantation[J].J Hematol Oncol,2016,9(1):118.
[10]BERRANGER A,COUSIEN A,PETIT,et al.Impact on long-term OS of conditioning regimen in allogeneic BMT for children with AML in first CR[J].Bone Marrow Transplant,2014(47):382-388.
[11]雷美清,刘立民,吴德沛.慢性移植物抗宿主病研究进展[J].中华血液学杂志,2016,37(1):79-82.
[12]WANG Y,LIU Q F,XU L P,et al.haploidentical vs identical-sibling transplant for AML in remission:a multicenter,prospective study[J].Blood,2015,125(25):3956-3962.
[13]章忠明,赖永榕,李桥川,等.非血缘异基因造血干细胞移植的死因分析[J].中国现代医学杂志,2011,21(28):3581-3583.
[14]黄清昕,涂三芳,黄睿,等.异基因造血干细胞移植治疗100例白血病的临床总结[J].中国实验血液学杂志,2016,24(2):556-561.
[15]ORAN B,JORGENSEN J L,MARIN D,et al.Pre-transplantation minimal residual disease with cytogenetic and molecular diagnostic features improves risk stratification in acute myeloid leukemia[J].Haematologica,2017,102(1):110-117.
[16]舒晓艳,闫侠芳,董磊,等.异基因造血干细胞移植后白血病复发的危险因素分析和治疗[J].中国实验血液学杂志,2016,24(4):1137-1142.
[2] MICHAEL M,CLAUDIA L,JAKOB P.Novel therapeutic options in acute myeloid leukemia[J].Leuk Res Rep,2016(40):39-49.
[3]杨贞,田骇,徐杨,等.异基因造血干细胞移植治疗Fins样酪氨酸激酶3基因内部串联重复(FLT3-ITD)阳性的急性髓性白血病的疗效分析[J].中华内科杂志,2005,53(2):94-98.
[4] HASSAN S,UMBERTO F,UDAY D,et al.myeloablative versus reduced-intensity conditioning in patients with myeloid malignancies:apropensity score-matched analysis[J].Biol Blood Marrow Transplant,2016(22):2270-2275.
[5] GIOVANNA L,MYRIAM L,ERIC B,et al.impact of conditioning regimen on outcomes for children with acute myeloid leukemia undergoing transplantation in first complete remission.An analysis on behalf of the pediatric disease working party of the European group for blood and marrow transplantation[J].Biol Blood Marrow Transplant,2017(23):467-474.
[6] LAI Y,MA J,SCHWARZENBERGER P,et al.Combination of CsA,MTX and low-dose,short-course mycophenolate mofetil for GVHD prophylaxis[J].Bone Marrow Transplant,2009,43(1):61-67.
[7] FIONAL D,ANDREW C,PERSIS A,et al.Diagnosis and management of acute graft-versus-host disease[J].Br J Haematol,2012,158(1):30-45.
[8] MADANH J,HILDEGARD T G,MUKTA A,et al.National institutes of health consensus development project on criteria for clinical trials in chronic graft-versus-host disease:I.the 2014diagnosis and staging working group report[J].Biol Blood Marrow Transplant,2015,21(3):389-401.
[9] SHIMONI A,LABOPIN M,SAVANI B,et al.Long-term survival and late events after allogeneic stem cell transplantation from HLA-matched siblings for acute myeloid leukemia with myeloablative compared to reduced-intensity conditioning:a report on behalf of the acute leukemia working party of European group for blood and marrow transplantation[J].J Hematol Oncol,2016,9(1):118.
[10]BERRANGER A,COUSIEN A,PETIT,et al.Impact on long-term OS of conditioning regimen in allogeneic BMT for children with AML in first CR[J].Bone Marrow Transplant,2014(47):382-388.
[11]雷美清,刘立民,吴德沛.慢性移植物抗宿主病研究进展[J].中华血液学杂志,2016,37(1):79-82.
[12]WANG Y,LIU Q F,XU L P,et al.haploidentical vs identical-sibling transplant for AML in remission:a multicenter,prospective study[J].Blood,2015,125(25):3956-3962.
[13]章忠明,赖永榕,李桥川,等.非血缘异基因造血干细胞移植的死因分析[J].中国现代医学杂志,2011,21(28):3581-3583.
[14]黄清昕,涂三芳,黄睿,等.异基因造血干细胞移植治疗100例白血病的临床总结[J].中国实验血液学杂志,2016,24(2):556-561.
[15]ORAN B,JORGENSEN J L,MARIN D,et al.Pre-transplantation minimal residual disease with cytogenetic and molecular diagnostic features improves risk stratification in acute myeloid leukemia[J].Haematologica,2017,102(1):110-117.
[16]舒晓艳,闫侠芳,董磊,等.异基因造血干细胞移植后白血病复发的危险因素分析和治疗[J].中国实验血液学杂志,2016,24(4):1137-1142.