异基因造血干细胞移植治疗髓系恶性血液病移植前临床特征与预后的相关性研究
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摘要
目的 :回顾性分析髓系白血病接受异基因造血干细胞移植(allogeneic hematopoietic stem cell transplantation,allo-HSCT)患者的预后相关因素。方法 :纳入175例接受allo-HSCT治疗患者,其中男性105例,女性70例,中位年龄37(28,46)岁,急性髓系白血病(acute myeloid leukemia,AML)145例,骨髓增生异常综合征(myelodysplasia syndrome,MDS)30例。根据移植前疾病状态将患者分为早期和进展期2组。早期患者包括AML第1次完全缓解(first complete remission,CR1)期和低中危MDS共116例;进展期患者包括AML非CR1期和高危MDS共59例。所有患者按照欧洲血液和骨髓移植组(European Group for Blood and Marrow Transplantation,EBMT)移植评分分为低危组(EBMT积分0~2分)86例和高危组(EBMT积分≥3分)89例。allo-HSCT干细胞供体来源为人类白细胞抗原(human leukocyte antigen,HLA)全相合同胞供体(Sib)85例,HLA相合非血缘供体(mismatched unrelated donor,MUD)64例和亲缘半相合(Haplo)26例。单因素分析患者年龄、性别、移植前疾病阶段、EBMT积分、供者来源对移植后整体生存(overall survival,OS)率、无事件生存(event free survival,EFS)率、非复发死亡率(non relapse mortality,NRM)和复发率(relapse rate,RR)的影响。结果 :所有患者中位随访12.7(3.9,45.1)个月,预期3年OS率、EFS率、NRM和RR分别为51.4%±4.0%、46.8%±4.0%、31.6%±3.7%和29.0%±4.4%。其中疾病早期移植与进展期移植2组,EBMT积分低危和高危2组OS率、EFS率、RR、NRM差异均有统计学意义(均P<0.05)。在所有移植患者或疾病早期移植组和进展期移植组中供体来源移植后OS率等指标差异均无统计学意义。结论:移植前状态及EBMT积分对髓系白血病接受allo-HSCT的整体疗效具有重要意义,不同移植供者移植后疗效相近。
Objective To evaluate the impact of pre-transplantation characteristics on treatment outcome in patents with myeloid malignancies undergoing allogeneic hematopoietic stem cell transplantation(allo-HSCT). Methods A total of175 patients with myeloid malignancies were enrolled, including 105 male and 70 female patients with median age of 37;145 patients were diagnosed as acute myeloid leukemia(AML) and 30 as myelodysplasia syndrome(MDS). According to the disease status at transplantation, 116 patients were in early stage including AML patients in 1 st clinical remission(CR1)and low to intermediate risk MDS, while other 59 patients with advanced disease including AML in non CR1, and high-risk MDS. All the patients were divided into low-risk or high-risk according to the European Group for Blood and Marrow Transplantation(EBMT) score(0-2, n=86 or≥3, n=89). As to the donor type, 85 patients received allo-HSCT from human leukocyte antigen(HLA) matched sibling donors(Sib), 64 from HLA-matched unrelated donors(MUD) and 26 from haploidentical donor(Haplo). Univariate analysis was performed to identify the potential prognostic factors of allo-HSCT in terms of overall survival(OS), event-free survival(EFS), non-relapse mortality(NRM), relapse rate(RR). Results The median follow-up of all 175 patients was 12.7 months with an estimated 3-year OS, EFS, NRM and RR of 51.4% ±4.0%,46.8% ±4.0%, 31.6% ±3.7% and 29.0% ±4.4%, respectively. The clinical outcome in OS, EFS, NRM and RR between patients transplanted at early stage and advanced stage, or patients with low-risk EBMT score versus high-risk EBMT score was differed significantly. For all patients, either with early stage or advanced stage, or with different EBMT score,the transplantation outcome was not significantly different between different donor types. Conclusions Pre-transplantation disease status and EBMT score were the important prognostic factors for patients with myeloid malignancies undergoing allo-HSCT. The selection of donor type did not have significant influence on outcome of allo-HSCT.
Objective To evaluate the impact of pre-transplantation characteristics on treatment outcome in patents with myeloid malignancies undergoing allogeneic hematopoietic stem cell transplantation(allo-HSCT). Methods A total of175 patients with myeloid malignancies were enrolled, including 105 male and 70 female patients with median age of 37;145 patients were diagnosed as acute myeloid leukemia(AML) and 30 as myelodysplasia syndrome(MDS). According to the disease status at transplantation, 116 patients were in early stage including AML patients in 1 st clinical remission(CR1)and low to intermediate risk MDS, while other 59 patients with advanced disease including AML in non CR1, and high-risk MDS. All the patients were divided into low-risk or high-risk according to the European Group for Blood and Marrow Transplantation(EBMT) score(0-2, n=86 or≥3, n=89). As to the donor type, 85 patients received allo-HSCT from human leukocyte antigen(HLA) matched sibling donors(Sib), 64 from HLA-matched unrelated donors(MUD) and 26 from haploidentical donor(Haplo). Univariate analysis was performed to identify the potential prognostic factors of allo-HSCT in terms of overall survival(OS), event-free survival(EFS), non-relapse mortality(NRM), relapse rate(RR). Results The median follow-up of all 175 patients was 12.7 months with an estimated 3-year OS, EFS, NRM and RR of 51.4% ±4.0%,46.8% ±4.0%, 31.6% ±3.7% and 29.0% ±4.4%, respectively. The clinical outcome in OS, EFS, NRM and RR between patients transplanted at early stage and advanced stage, or patients with low-risk EBMT score versus high-risk EBMT score was differed significantly. For all patients, either with early stage or advanced stage, or with different EBMT score,the transplantation outcome was not significantly different between different donor types. Conclusions Pre-transplantation disease status and EBMT score were the important prognostic factors for patients with myeloid malignancies undergoing allo-HSCT. The selection of donor type did not have significant influence on outcome of allo-HSCT.
引文
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[3]苏秀华,姚剑峰,张桂新,等.异基因造血干细胞移植治疗难治/复发急性髓系白血病的疗效及预后因素分析[J].中华血液学杂志,2017,38(12):1024-1030.
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[7]Wang HT,Chang YJ,Xu LP,et al.EBMT risk score can predict the outcome of leukaemia after unmanipulated haploidentical blood and marrow transplantation[J].Bone Marrow Transplant,2014,49(7):927-933.
[8]胡炯,章卫平,杨丹,等.EBMT积分在异基因造血干细胞移植治疗慢性粒细胞白血病中的预后价值[J].中华血液学杂志,2011,32(2):75-78.
[9]De Souza CA,Vigorito AC,Ruiz MA,et al.Validation of the EBMT risk score in chronic myeloid leukemia in Brazil and allogeneic transplant outcome[J].Haematologica,2005,90(2):232-237.
[10]Potdar R,Varadi G,Fein J,et al.Prognostic scoring systems in allogeneic hematopoietic stem cell transplantation:where do we stand?[J].Biol Blood Marrow Transplant,2017,23(11):1839-1846.
[11]Cornelissen JJ,Gratwohl A,Schlenk RF,et al.The European Leukemia Net AML Working Party consensus statement on allogeneic HSCT for patients with AML in remission:an integrated-risk adapted approach[J].Nat Rev Clin Oncol,2012,9(10):579-590.
[12]Salvatore D,Labopin M,Ruggeri A,et al.Outcomes of hematopoietic stem cell transplantation from unmanipulated haploidentical versus matched sibling donor in patients with acute myeloid leukemia in first complete remission with intermediate or high-risk cytogenetics:a study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation[J].Haematologica,2018.[Epub ahead of print].
[13]Slade M,Fakhri B,Savani BN,et al.Halfway there:the past,present and future of haploidentical transplantation[J].Bone Marrow Transplant,2016,52(1):1-6.
[14]Tsirigotis P,Byrne M,Schmid C,et al.Relapse of AMLafter hematopoietic stem cell transplantation:methods of monitoring and preventive strategies.A review from the ALWP of the EBMT[J].Bone Marrow Transplant,2016,51(11):1431-1438.
[15]Savani BN.Transplantation in AML CR1[J].Blood,2010,116(11):1822-1823.
[16]Elsawy M,Sorror ML.Up-to-date tools for risk assessment before allogeneic hematopoietic cell transplantation[J].Bone Marrow Transplant,2016,51(10):1283-1300.
[2]Niederwieser D,Baldomero H,Szer J,et al.Hematopoietic stem cell transplantation activity worldwide in 2012and a SWOT analysis of the Worldwide Network for Blood and Marrow Transplantation Group including the global survey[J].Bone Marrow Transplant,2016,51(6):778-785.
[3]苏秀华,姚剑峰,张桂新,等.异基因造血干细胞移植治疗难治/复发急性髓系白血病的疗效及预后因素分析[J].中华血液学杂志,2017,38(12):1024-1030.
[4]Gooley TA,Chien JW,Pergam SA,et al.Reduced mortality after allogeneic hematopoietic-cell transplantation[J].N Engl J Med,2010,363(22):2091-2101.
[5]Gratwohl A,Brand R,Apperley J,et al.Allogeneic hematopoietic stem cell transplantation for chronic myeloid leukemia in Europe 2006:transplant activity,long-term data and current results[J].Haematologica,2006,91(4):513-521.
[6]El-Ghammaz AMS,El-Razzaz MK.Risk factors influencing outcome of acute leukemia patients who experience relapse after allogeneic hematopoietic stem-cell transplantation[J].Clin Lymphoma Myeloma Leuk,2018,18(4):e183-e190.
[7]Wang HT,Chang YJ,Xu LP,et al.EBMT risk score can predict the outcome of leukaemia after unmanipulated haploidentical blood and marrow transplantation[J].Bone Marrow Transplant,2014,49(7):927-933.
[8]胡炯,章卫平,杨丹,等.EBMT积分在异基因造血干细胞移植治疗慢性粒细胞白血病中的预后价值[J].中华血液学杂志,2011,32(2):75-78.
[9]De Souza CA,Vigorito AC,Ruiz MA,et al.Validation of the EBMT risk score in chronic myeloid leukemia in Brazil and allogeneic transplant outcome[J].Haematologica,2005,90(2):232-237.
[10]Potdar R,Varadi G,Fein J,et al.Prognostic scoring systems in allogeneic hematopoietic stem cell transplantation:where do we stand?[J].Biol Blood Marrow Transplant,2017,23(11):1839-1846.
[11]Cornelissen JJ,Gratwohl A,Schlenk RF,et al.The European Leukemia Net AML Working Party consensus statement on allogeneic HSCT for patients with AML in remission:an integrated-risk adapted approach[J].Nat Rev Clin Oncol,2012,9(10):579-590.
[12]Salvatore D,Labopin M,Ruggeri A,et al.Outcomes of hematopoietic stem cell transplantation from unmanipulated haploidentical versus matched sibling donor in patients with acute myeloid leukemia in first complete remission with intermediate or high-risk cytogenetics:a study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation[J].Haematologica,2018.[Epub ahead of print].
[13]Slade M,Fakhri B,Savani BN,et al.Halfway there:the past,present and future of haploidentical transplantation[J].Bone Marrow Transplant,2016,52(1):1-6.
[14]Tsirigotis P,Byrne M,Schmid C,et al.Relapse of AMLafter hematopoietic stem cell transplantation:methods of monitoring and preventive strategies.A review from the ALWP of the EBMT[J].Bone Marrow Transplant,2016,51(11):1431-1438.
[15]Savani BN.Transplantation in AML CR1[J].Blood,2010,116(11):1822-1823.
[16]Elsawy M,Sorror ML.Up-to-date tools for risk assessment before allogeneic hematopoietic cell transplantation[J].Bone Marrow Transplant,2016,51(10):1283-1300.