单倍体相合造血干细胞移植治疗48例恶性血液病患者的临床分析
|
摘要
目的:探究恶性血液病患者行单倍体相合造血干细胞移植(haplo-HSCT)的临床疗效。方法:本研究共纳入48例患者,均采用粒细胞集落刺激因子动员外周血干细胞作为移植物的非体外去T细胞移植模式。结果:48例患者均获粒系及巨核系重建,中性粒细胞植活的中位时间为14(9～38)d,血小板植活的中位时间为16.5(9～49)d。移植后第100天时急性移植物抗宿主病(aGVHD)累积发生率为16.5%,其中Ⅲ～Ⅳ度aGVHD累积发生率为6.7%。43例患者移植后存活时间超过100d,慢性移植物抗宿主病(cGVHD)的2年累积发生率为28.6%,其中广泛型cGVHD为12.6%。2年累积复发率及累积非复发死亡率分别为23.7%、30.2%。2年及3年累积总体生存率和累积无病生存率分别为52.6%和44.5%、37.5%和33.8%。结论:非体外去T细胞的haplo-HSCT对恶性血液病患者的治疗有效,且仅用外周血干细胞与骨髓+外周血干细胞做移植物在haploHSCT中的效果无明显差异。
Objective:To investigate the clinical efficacy of haploidentical hematopoietic stem cell transplantation(haplo-HSCT)in patients with malignant hematopathy.Method:A total of 48 patients were enrolled in this study.The granulocyte colony-stimulating factor was used to mobilize peripheral blood stem cells as grafts without in vitro T cell depletion.Result:All the 48 patients achieved neutrophil recovery and megakaryocyte reconstitution.The median time of neutrophil engraftment was 14(9 to 38)days.The median time of platelet engraftment was16.5(9 to 49)days.The cumulative incidence of acute GVHD(aGVHD)on the first 100 days after transplantation(+100 d)was 16.5%,and that of gradeⅢ-ⅣaGVHD was 6.7%.Forty-three patients were survived beyond the+100 d,the 2-year cumulative incidence of total chronic GVHD(cGVHD)was 28.6%,and that of extensive cGVHD was 12.6%.The 2-year cumulative incidences of relapse and nonrelapse mortality were 23.7% and30.2%,respectively.The cumulative incidences of overall survival and disease-free survival at 2 and 3 years were52.6% and 44.5%,37.5% and 33.8%,respectively.Conclusion:The results showed that haplo-HSCT without in vitro T cell depletion is an effective method for hematologic malignancies,and there is no significant difference in the effect of grafts with peripheral blood stem cells and bone marrow + peripheral blood stem cells in haploHSCT.
Objective:To investigate the clinical efficacy of haploidentical hematopoietic stem cell transplantation(haplo-HSCT)in patients with malignant hematopathy.Method:A total of 48 patients were enrolled in this study.The granulocyte colony-stimulating factor was used to mobilize peripheral blood stem cells as grafts without in vitro T cell depletion.Result:All the 48 patients achieved neutrophil recovery and megakaryocyte reconstitution.The median time of neutrophil engraftment was 14(9 to 38)days.The median time of platelet engraftment was16.5(9 to 49)days.The cumulative incidence of acute GVHD(aGVHD)on the first 100 days after transplantation(+100 d)was 16.5%,and that of gradeⅢ-ⅣaGVHD was 6.7%.Forty-three patients were survived beyond the+100 d,the 2-year cumulative incidence of total chronic GVHD(cGVHD)was 28.6%,and that of extensive cGVHD was 12.6%.The 2-year cumulative incidences of relapse and nonrelapse mortality were 23.7% and30.2%,respectively.The cumulative incidences of overall survival and disease-free survival at 2 and 3 years were52.6% and 44.5%,37.5% and 33.8%,respectively.Conclusion:The results showed that haplo-HSCT without in vitro T cell depletion is an effective method for hematologic malignancies,and there is no significant difference in the effect of grafts with peripheral blood stem cells and bone marrow + peripheral blood stem cells in haploHSCT.
引文
[1] Apperley J,Niederwieser D,Huang XJ,et al.Haploidentical hematopoietic stem cell transplantation:a global overview comparing Asia,the European Union,and the United States[J].Biol Blood Marrow Transplant,2016,22:S15-S18.
[2] Kurokawa T,Ishiyama K,Ozaki J,et al.Haploidentical hematopoietic stem cell transplantation to adults with hematologic malignancies:analysis of 66cases at a single Japanese center[J].Int J Hematol,2010,91:661-669.
[3]王顺清.HLA单倍体相合造血干细胞移植研究进展[J].实用医学杂志,2016,32(10):1553-1555.
[4] Xu LP,Wu DP,Han MZ,et al.A review of hematopoietic cell transplantation in China:data and trends during 2008-2016[J].Bone Marrow Transplant,2017,52:1512-1518.
[5]张之南,沈悌.血液病诊断及疗效标准[M].3版.北京:科学出版社,2007:103-234.
[6] Martínez C,Gayoso J,Canals C,et al.Post-transplantation cyclophosphamide-based haploidentical transplantation as alternative to matched sibling or unrelated donor transplantation for hodgkin lymphoma:A Registry Study of the Lymphoma Working Party of the European Society for Blood and Marrow Transplantation[J].J Clin Oncol,2017,35:3425-3432.
[7] Wang Y,Liu DH,Liu KY,et al.Long-term follow-up of haploidentical hematopoietic stem cell transplantation without in vitro T cell depletion for the treatment of leukemia:nine years of experience at a single center[J].Cancer,2013,119:978-985.
[8] Wang Y,Liu QF,Xu LP,et al.Haploidentical vs identical-sibling transplant for AML in remission:a multicenter,prospective study[J].Blood,2015,125:3956-3962.
[9] Lu RN,Miao KR,Zhang R,et al.Haploidentical hematopoietic stem cell transplantation following myeloablative conditioning regimens in hematologic diseases with G-CSF-mobilized peripheral blood stem cells grafts without T cell depletion:a single center report of 38cases[J].Med Oncol,2014,31:81.
[10]Yu S,Fan Q,Sun J,et al.Haploidentical transplantation without in vitro T-cell depletion results in outcomes equivalent to those of contemporaneous matched sibling and unrelated donor transplantation for acute leukemia[J].Medicine(Baltimore),2016,95:e2973.
[11]Castagna L,Crocchiolo R,Furst S,et al.Bone marrow compared with peripheral blood stem cells for haploidentical transplantation with a nonmyeloablative conditioning regimen and post-transplantation cyclophosphamide[J].Biol Blood Marrow Transplant,2014,20:724-729.
[12] Gulbas Z.Haploidentical stem cell transplantationbone marrow vs peripheral blood[J].Transfus Apher Sci,2018,57:168-170.
[13]赵晓甦,许兰平,刘代红,等.成人人类白细胞抗原全相合与不相合造血干细胞移植后急性移植物抗宿主病的临床特点与预后[J].中华内科杂志,2014,53(1):35-39.
[14]Baron F,Mohty M,Blaise D,et al.Anti-thymocyte globulin as graft-versus-host disease prevention in the setting of allogeneic peripheral blood stem cell transplantation:a review from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation[J].Haematologica,2017,102:224-234.
[15]Lin X,Lu ZG,Song CY,et al.Long-term outcome of HLA-haploidentical hematopoietic stem cell transplantation without in vitro T-cell depletion based on an FBCA conditioning regimen for hematologic malignancies[J].Bone Marrow Transplantation,2015,50:1092-1097.
[16]Yan CH,Xu LP,Wang FR,et al.Causes of mortality after haploidentical hematopoietic stem cell transplantation and the comparison with HLA-identical sibling hematopoietic stem cell transplantation[J].Bone Marrow Transplant,2016,51:391-397.
[17]Liu Z,Zhang Y,Xiao H,et al.Cotransplantation of bone marrow-derived mesenchymal stem cells in haploidentical hematopoietic stem cell transplantation in patients with severe aplastic anemia:an interim summary for a multicenter phase II trial results[J].Bone Marrow Transplant,2017,52:1080.
[18]Ruggeri A,Roth-Guepin G,Battipaglia G,et al.Incidence and risk factors for hemorrhagic cystitis in unmanipulated haploidentical transplant recipients[J].Transpl Infect Dis,2015,17:822-830.
[19]Gilis L,Morisset S,Billaud G,et al.High burden of BK virus-associated hemorrhagic cystitis in patients undergoing allogeneic hematopoietic stem cell transplantation[J].Bone Marrow Transplant,2014,49:664-670.
[20]Chang YJ,Zhao XY,Huang XJ.Immune reconstitution after haploidentical hematopoietic stem cell transplantation[J].Biol Blood Marrow Transplant,2014,20:440-449.
[21]Wang Y,Chang YJ,Xu LP,et al.Who is the best donor for a related HLA haplotype-mismatched transplant?[J].Blood,2014,124:843-850.
[22]Ma YR,Xu LP,Zhang XH,et al.Comparable post-relapse outcomes between haploidentical and matched related donor allogeneic stem cell transplantation[J].Bone Marrow Transplant,2017,52:409-414.
[23]王昱.供者淋巴细胞输注防治异基因造血干细胞移植后复发[J].临床血液学杂志,2017,30(9):669-672.
[2] Kurokawa T,Ishiyama K,Ozaki J,et al.Haploidentical hematopoietic stem cell transplantation to adults with hematologic malignancies:analysis of 66cases at a single Japanese center[J].Int J Hematol,2010,91:661-669.
[3]王顺清.HLA单倍体相合造血干细胞移植研究进展[J].实用医学杂志,2016,32(10):1553-1555.
[4] Xu LP,Wu DP,Han MZ,et al.A review of hematopoietic cell transplantation in China:data and trends during 2008-2016[J].Bone Marrow Transplant,2017,52:1512-1518.
[5]张之南,沈悌.血液病诊断及疗效标准[M].3版.北京:科学出版社,2007:103-234.
[6] Martínez C,Gayoso J,Canals C,et al.Post-transplantation cyclophosphamide-based haploidentical transplantation as alternative to matched sibling or unrelated donor transplantation for hodgkin lymphoma:A Registry Study of the Lymphoma Working Party of the European Society for Blood and Marrow Transplantation[J].J Clin Oncol,2017,35:3425-3432.
[7] Wang Y,Liu DH,Liu KY,et al.Long-term follow-up of haploidentical hematopoietic stem cell transplantation without in vitro T cell depletion for the treatment of leukemia:nine years of experience at a single center[J].Cancer,2013,119:978-985.
[8] Wang Y,Liu QF,Xu LP,et al.Haploidentical vs identical-sibling transplant for AML in remission:a multicenter,prospective study[J].Blood,2015,125:3956-3962.
[9] Lu RN,Miao KR,Zhang R,et al.Haploidentical hematopoietic stem cell transplantation following myeloablative conditioning regimens in hematologic diseases with G-CSF-mobilized peripheral blood stem cells grafts without T cell depletion:a single center report of 38cases[J].Med Oncol,2014,31:81.
[10]Yu S,Fan Q,Sun J,et al.Haploidentical transplantation without in vitro T-cell depletion results in outcomes equivalent to those of contemporaneous matched sibling and unrelated donor transplantation for acute leukemia[J].Medicine(Baltimore),2016,95:e2973.
[11]Castagna L,Crocchiolo R,Furst S,et al.Bone marrow compared with peripheral blood stem cells for haploidentical transplantation with a nonmyeloablative conditioning regimen and post-transplantation cyclophosphamide[J].Biol Blood Marrow Transplant,2014,20:724-729.
[12] Gulbas Z.Haploidentical stem cell transplantationbone marrow vs peripheral blood[J].Transfus Apher Sci,2018,57:168-170.
[13]赵晓甦,许兰平,刘代红,等.成人人类白细胞抗原全相合与不相合造血干细胞移植后急性移植物抗宿主病的临床特点与预后[J].中华内科杂志,2014,53(1):35-39.
[14]Baron F,Mohty M,Blaise D,et al.Anti-thymocyte globulin as graft-versus-host disease prevention in the setting of allogeneic peripheral blood stem cell transplantation:a review from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation[J].Haematologica,2017,102:224-234.
[15]Lin X,Lu ZG,Song CY,et al.Long-term outcome of HLA-haploidentical hematopoietic stem cell transplantation without in vitro T-cell depletion based on an FBCA conditioning regimen for hematologic malignancies[J].Bone Marrow Transplantation,2015,50:1092-1097.
[16]Yan CH,Xu LP,Wang FR,et al.Causes of mortality after haploidentical hematopoietic stem cell transplantation and the comparison with HLA-identical sibling hematopoietic stem cell transplantation[J].Bone Marrow Transplant,2016,51:391-397.
[17]Liu Z,Zhang Y,Xiao H,et al.Cotransplantation of bone marrow-derived mesenchymal stem cells in haploidentical hematopoietic stem cell transplantation in patients with severe aplastic anemia:an interim summary for a multicenter phase II trial results[J].Bone Marrow Transplant,2017,52:1080.
[18]Ruggeri A,Roth-Guepin G,Battipaglia G,et al.Incidence and risk factors for hemorrhagic cystitis in unmanipulated haploidentical transplant recipients[J].Transpl Infect Dis,2015,17:822-830.
[19]Gilis L,Morisset S,Billaud G,et al.High burden of BK virus-associated hemorrhagic cystitis in patients undergoing allogeneic hematopoietic stem cell transplantation[J].Bone Marrow Transplant,2014,49:664-670.
[20]Chang YJ,Zhao XY,Huang XJ.Immune reconstitution after haploidentical hematopoietic stem cell transplantation[J].Biol Blood Marrow Transplant,2014,20:440-449.
[21]Wang Y,Chang YJ,Xu LP,et al.Who is the best donor for a related HLA haplotype-mismatched transplant?[J].Blood,2014,124:843-850.
[22]Ma YR,Xu LP,Zhang XH,et al.Comparable post-relapse outcomes between haploidentical and matched related donor allogeneic stem cell transplantation[J].Bone Marrow Transplant,2017,52:409-414.
[23]王昱.供者淋巴细胞输注防治异基因造血干细胞移植后复发[J].临床血液学杂志,2017,30(9):669-672.