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TBI为主的不含ATG的清髓性预处理方案在非血缘脐血移植治疗成人恶性血液病中的应用 被引量:14

Unrelated umbilical cord blood transplantation with TBI/Ara-c/CY non-ATG conditioning regimen for adults with hematologic malignancies
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摘要 目的分析采用全身照射(TBI)为主的不含抗胸腺细胞球蛋白(ATG)的清髓性预处理方案进行非血缘脐血移植(UCBT)治疗成人恶性血液病的安全性和疗效。方法2006年9月至2011年5月,单中心采用不含ATG由TBI、阿糖胞苷(Ara-c)、环磷酰胺(CY)组成的清髓性预处理方案进行UCBT治疗40例成人恶性血液病患者。患者平均年龄(23±6)岁,平均体重(58±9)kg。40例患者中高危难治患者35例(87.5%),进展期进行移植患者15例(37.5%)。单份脐血移植23例,双份脐血移植17例。75.0%(30/40)患者存在HLA1-2个位点不合。移植物抗宿主病(GVHD)预防采用环孢素A联合霉酚酸酯方案。结果受者输入脐血总有核细胞平均数为(4.1±1.1)×10^7/kg,CD34^+细胞平均数为(2.4±1.0)×10^5/kg。40例患者全部获得植入,植入率100%。中性粒细胞绝对值≥0.5×10^9/L的平均时间为(20±5)d,血小板≥20×10^9/L的平均时间为(384±12)d。40例中23例(57.5%)发生急性GVHD,其中Ⅲ-Ⅳ度4例(10.0%)。可评估的35例患者中8例(22.9%)发生慢性GVHD,均为局限型。12.5%(5/40)患者复发。存活患者中位随访时间19.8(4.6-55.0)个月。100d和1年移植相关病死率分别为15.0%、35.0%。主要死亡原因为严重肺部感染和重度急性GVHD。2年无病生存率和总生存率均为58.8%。疾病进展期与缓解期进行移植的患者2年累计生存率分别为48.6%和63.8%,差异无统计学意义(X^2=0.304,P=0.582)。结论采用TBI/Ara-c/CY预处理方案行成人UCBT耐受性好,全部患者均获得稳定植入,降低早期移植相关死亡。该方案用于高危、难治和进展期患者移植后复发率较低,慢性GVHD发生率低并均为局限型,获得较理想的生存率。 Objective To retrospectively analyze the curative efficacy of umbilical cord blood transplantation (UCBT) with improved myeloablative conditioning regimen (total body irradiation (TBI)/ cytosine arabinoside (Ara-e) / eyclophosphamide ( CY ) without antithymocyte globulin (ATG) ) in adult patients with hematological malignancies. Methods Forty consecutive adult patients with hematological malignancies received improved myeloablative unrelated CBT at a single center from September 2006 to May 2011. Their average age was (23± 6) years and the average weight (58 ± 9) kg. Thirty-five(87.5% ) patients were high-risk and 15 (37. 5% )at the advanced disease status at pre-transplantation. They received 1 ( n = 23) or 2 ( n = 17 ) cord blood units. Seventy-five percent of them were transplanted with 1/2- human leukocyte antigen mismatched uniL The conditioning regimen consisted of 12 Gy TBI, granuloeyte colony- stimulating factor (G-CSF) plus Ara-c and CY without ATG. All patients received a combination ofcyclosporine (CsA) and mycophenolate mofetil (MMF) for the prophylaxis of graft-versus-host disease (GVHD). Results For the entire group of patients, the average cell doses infused were (4. 1 ±1.1 ) ×10^7 total nucleated cells/kg and (2.4 ±1.0) × 105 CD34^± cells/kg. All patients acquired engraftment with an implantation rate of 100%. The average time of absolute neutrophil count ( ANC ) ≥ 0. 5 ×10^9/L was (20 ±5 ) days and the average time of platelet ≥20× 10^9/L was (38 ± 12 )days. Acute GVHD occurred in 23 patients(57.5% )and 4 (10. 0% ) were of grade Ⅲ -Ⅳ. Chronic GVHD occurred in 22. 9% (8/35) evaluable patients. Relapse occurred in 12. 5% (5/40) patients. During a median follow-up period of 19.8 (range 4. 6 -55.0) months,the transplantation-related mortality was 15.0% (6/40) within 100 days and 35.0% (14/40) within 1 year. The main causes of mortality were pneumonia and severe acute GVHD. Two-year overall survival (OS) or disease-free survival was 58. 8% and 58. 8% , respectively. Two-year OS for patients with advanced or complete remission disease was 48. 6% and 63.8%, respectively. Conclusions The TBI/Ara-c/CY myeloablative conditioning regimen is well-tolerated and capable of establishing sustained donor cell engraftment and decreasing the risks of transplant-related death in adults with hematologic malignancies. For the high-risk and advanced patients, it may reduce the occurrences of relapse and chronic GVHD.
出处 《中华医学杂志》 CAS CSCD 北大核心 2012年第24期1660-1664,共5页 National Medical Journal of China
基金 安徽省“十二五”科技攻关(11010402164) 安徽省卫生厅医学科研重点项目(2010A005)
关键词 移植预处理 脐血干细胞移植 白血病 Transplantation conditioning Cord blood stem cell transplantation Leukemia
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参考文献14

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同被引文献141

  • 1黄晓军,刘代红,许兰平,韩伟,江倩,陈育红,张耀臣,刘开彦,鲍立,陆道培.主要ABO血型不合异基因造血干细胞移植后纯红细胞再生障碍[J].中华血液学杂志,2005,26(9):548-550. 被引量:26
  • 2黄晓军,许兰平.造血干细胞移植在血液系统疾病的临床应用[J].基础医学与临床,2005,25(10):883-888. 被引量:3
  • 3夏凌辉,邹萍,胡俊斌,方峻,游泳,郭涛,刘芳,张纯,江汇娟,宋善俊.造血干细胞移植后并发感染121例的临床分析[J].中华器官移植杂志,2006,27(11):685-688. 被引量:10
  • 4黄晓军.造血干细胞移植感染诊治策略[J].中华医学杂志,2006,86(42):2953-2956. 被引量:12
  • 5Butler MG, Menitove JE. Umbilical cord blood banking: an update [J]. J Assist Reprod Genet ,2011,28:669 - 676.
  • 6Rocha V, Wagner JE, Sobocinski K, et al. Comparison of graft-ver- se, s-host disease in children transplanted with HLA identical sibling umbilical cord blood versus HLA identical sibling bone marrnw transplant[ J]. N Engl J Med ,2000,342 : 1846 - 1854.
  • 7Eapen M, Rubinstein P,Zhang M J, et al. Outcomes of transplantation of unrelated donor umbilical cord blood and bone marrow in children with acute leukaemia : a comparison study [ J ]. Lancet, 2007,369 : 1947 - 1954.
  • 8Kurtzberg J,Prasad VK, Carter SL, et al. Results of the Cord BloodTransplantation Study(COBLT) : clinical outcomes of unrelated do- nor umbilical cord blood transplantation in pediatric patients with hematologic malignancies[J]. Blood,2008,112:4318 -4327.
  • 9Zheng C, Tang B, Tong J, et al. Unrelated cord blood transplantation for central nervous system relapse in high-risk childhood acute lyrn- phoblastie leukemia [ J ]. Ann Hematol, 2013 [ Epub ahead of print I :.
  • 10Rocha V, Labopin M, Sanz G, et al. Outcomes alter transplants of umbilical-cord blood. or bone marrow from unrelated donors in adults with acute leukemia[ J:. N Engl J Med ,2004,351:2276 -2285.

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