减低预处理剂量亲缘单倍体PBSCT治疗恶性血液肿瘤的临床研究
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摘要
目的减低预处理剂量亲缘间HLA单倍体相合外周血造血干细胞移植(RIC-haplo-PBSCT)治疗年轻体弱或高龄恶性血液肿瘤患者的疗效分析。方法根据入排标准纳入2013年7月-2016年11月在本中心治疗的12例恶性血液肿瘤患者,所有患者均采用以FAB+ATG(氟达拉滨+阿糖胞苷+马利兰+抗胸腺球蛋白)的减低剂量的预处理方案,输注供者高剂量不去T细胞PBSC,采用加强的移植物抗宿主病(GVHD)的预防方案及感染防控方案。结果所有患者均获得造血快速重建;10例患者在移植后15天获得完全供者嵌合,2例患者为混合嵌合并于移植后1月出现移植排斥。中位随访23.5月(3~53)月,1年总生存率(OS)为75%,1年无病生存率(DFS)为66.7%,1年复发率(RI)为18.5%,1年非复发死亡率(NRM)为18.1%。结论笔者独特的RIC-haplo-PBSCT方案获得较好的造血恢复、供体植入及生存,为高龄或年轻体弱难以耐受经典清髓移植且找不到HLA全相合供者的恶性血液肿瘤患者提供了更多的治疗机会。
Objective To evaluate the efficacy of related HLA-haploidentical peripheral hematopoietic stem cell transplantation following reduced intensity conditioning(RIC)regimen to treat the patients with hematological malignancies who were elder or with pre-existing comorbidities. Methods 12 Patients with hematological malignancies were enrolled from July 2013 to December 2016 treated in our Center. All patients received the RIC regimen consisting of fludarabine, cytarabine, Melphalan, and plus rabbit anti-human thymocyte globulin(ATG), transplanted with non T cell-depleted in vitro high dose peripheral hematopoietic stem cell.Graft versus host disease(GVHD)prophylaxis and infection prevention were intensively. Results Engraftment was observed in all patients(100%).Fifteen days after transplantation, 10 patients had complete donor chimerism and 2 patienets had mixed chimerism who converted to complete recipient chimerism at thirty days after transplantation. Patients were followed-up for a median of 23.5 months(range, 3-53 months). The Kaplan Meier estimates of one-year overall survival and disease free survival were 75% and 66.7%. The one-year cumulative incidence of relapse and non-relapse mortality were 18.5% and 18.1%. Conclusion Our unique transplantation pattern results in sustained engraftment and improved survival, which providing a new feasible curative therapy for those elder or with pre-existing comorbidities patients who are not suitable for myeloablative conditioning regimen, and do not have HLA-matched donor.
Objective To evaluate the efficacy of related HLA-haploidentical peripheral hematopoietic stem cell transplantation following reduced intensity conditioning(RIC)regimen to treat the patients with hematological malignancies who were elder or with pre-existing comorbidities. Methods 12 Patients with hematological malignancies were enrolled from July 2013 to December 2016 treated in our Center. All patients received the RIC regimen consisting of fludarabine, cytarabine, Melphalan, and plus rabbit anti-human thymocyte globulin(ATG), transplanted with non T cell-depleted in vitro high dose peripheral hematopoietic stem cell.Graft versus host disease(GVHD)prophylaxis and infection prevention were intensively. Results Engraftment was observed in all patients(100%).Fifteen days after transplantation, 10 patients had complete donor chimerism and 2 patienets had mixed chimerism who converted to complete recipient chimerism at thirty days after transplantation. Patients were followed-up for a median of 23.5 months(range, 3-53 months). The Kaplan Meier estimates of one-year overall survival and disease free survival were 75% and 66.7%. The one-year cumulative incidence of relapse and non-relapse mortality were 18.5% and 18.1%. Conclusion Our unique transplantation pattern results in sustained engraftment and improved survival, which providing a new feasible curative therapy for those elder or with pre-existing comorbidities patients who are not suitable for myeloablative conditioning regimen, and do not have HLA-matched donor.
引文
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[14]杨廷,江明.减低剂量预处理方案在亲缘HLA单倍体相合造血干细胞移植中的应用[J].中国组织工程研究,2015,19(6):955-958.
[15]Czerw T,Labopin M,Schmid C,et al.High CD3+and CD34+peripheral blood stem cell grafts content is associated with increased risk of graft-versus-host disease without beneficial effect on disease control after reducedintensity conditioning allogeneic transplantation from matched unrelated donors for acute myeloid leukemia-an analysis from the Acute Leukemia Work,ing Party of the European Society for Blood and Marrow Transplantation[J].Oncotarget.2016;7(19):27255-27266.
[16]Holtan SG,DeF or TE,Aleksandr L,et al.Composite end point of graft-versus-host disease-free,elapse-free survival after allogeneic hematopoietic cell transplantation[J].Blood.2015;125(8):1333-1338.
[2]Blaise D,Tabrizi R,Bother JM,et al.Randomized Study of 2 Reduced-Intensity Conditioning Strategies for Human Leukocyte Antigen-Matched,Related Allogeneic Peripheral Blood Stem Cell Transplantation:prospective clinical and socioeconomic evaluation[J].Cancer.2013;119(3):602-611.
[3]El-Jawahri A,Li S,Ballen KK,et al.Phase Ⅱ Trial of Reduced-Intensity Busulfan/Clofarabine Conditioning with Allogeneic Hematopoietic Stem Cell Transplantation for Patients with Acute Myeloid Leukemia,Myelodysplastic Syndromes,and Acute Lymphoid Leukemia[J].Biol Blood Marrow Transplant.2016;22(1):80-85.
[4]Armand P,Kim HT,Logan BR,et al.Validation and refinement of the disease risk index for allogeneic stem cell transplantation[J].Blood.2014;123:3664-3671.
[5]Slavin S,Nagler A,Naparstek E,et al.Nonmyeloablative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and nonmalignant hematologic diseases[J].Blood.1998;91(3):756-763.
[6]Shimoni A,Andelini B,Estey E,et al.Allogeneic transplantation for leukemia in patients older than 60 years:age should not exclude treatmentwith nonmyeloablative regimen[J].Blood.1999;94[Suppl 1]:710a.
[7]Mohty M,Jacot W,Faucher C,et al.Infectious complications following allogeneic HLA-identical sibling transplantation with antithymocyte globulin-based reduced intensity preparative regimen[J].Leukemia.2003;17(11):2168-2177.
[8]Le Bourgeois A,Lestang E,Guillaume T,et al.Prognostic impact of immune status and hematopoietic recovery before and after fludarabine,IV busulfan,and antithymocyte globulins(FB2 regimen)reduced-intensity conditioning regimen(RIC)allogeneic stem cell transplantation(allo-SCT)[J].Eur J Haematol.2013;90(3):177-186.
[9]Oudin C,Chevallier P,Furst S,et al.Reduced-toxicity conditioning prior to allogeneic stem cell transplantation improves outcome in patients with myeloid malignancies[J].Haematologica.2014;99(11):1762-1768.
[10]Storb R,Yu C,Zaucha JM,et a1.Stable mixed hematopoietic chimerism in dogs given donor an-tigen,CTLA4Ig,and 100 cG y total body irradiation before and pharmacologic immunosuppression after marrow transplant[J].Blood.1999;94(7):2523-2529.
[11]Scott BL,Sandmaier BM,Storer B,et al.Myeloablative vs nonmyeloablative allogeneic transplantation for patients with myelodysplastic syndrome or acute myelogenous leukemia with multilineage dysplasia:a retrospective analysis[J].Leukemia.2006;20(1):128-135.
[12]Gupta V,Daly A,Lipton JH,et a1.Nonmyeloablative stem cell transplantation for myelodysplastic syndrome or acute myeloid leukemia in patients 60 years or older[J].Biol Blood Marrow Transplant.2005;11(10):764-772.
[13]Wang DH,Ai HS,Yu CL,et al.HLA haploidentical allogenetic stem cells transplantation for refractory acute leukemia[J].Chin J Pract Intern Med.2005;25(9):821-822.
[14]杨廷,江明.减低剂量预处理方案在亲缘HLA单倍体相合造血干细胞移植中的应用[J].中国组织工程研究,2015,19(6):955-958.
[15]Czerw T,Labopin M,Schmid C,et al.High CD3+and CD34+peripheral blood stem cell grafts content is associated with increased risk of graft-versus-host disease without beneficial effect on disease control after reducedintensity conditioning allogeneic transplantation from matched unrelated donors for acute myeloid leukemia-an analysis from the Acute Leukemia Work,ing Party of the European Society for Blood and Marrow Transplantation[J].Oncotarget.2016;7(19):27255-27266.
[16]Holtan SG,DeF or TE,Aleksandr L,et al.Composite end point of graft-versus-host disease-free,elapse-free survival after allogeneic hematopoietic cell transplantation[J].Blood.2015;125(8):1333-1338.