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[采用TBI/Ara-c/CY非抗胸腺细胞球蛋白预处理方案的无关供者脐血移植治疗成人血液系统恶性肿瘤]

[Unrelated umbilical cord blood transplantation with TBI/Ara-c/CY non-ATG conditioning regimen for adults with hematologic malignancies].

作者信息

Sun Zi-min, Liu Hui-lan, Geng Liang-quan, Zhou Chen-yang, Wang Xing-bing, Ding Kai-yang, Tong Juan, Zhu Wei-bo, Liu Xin, Wang Zu-yi

机构信息

Department of Hematology, Affiliated Provincial Hospital, Anhui Medical University, Hefei 230001, China.

出版信息

Zhonghua Yi Xue Za Zhi. 2012 Jun 26;92(24):1660-4.

PMID:22944153
Abstract

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-c)/cyclophosphamide (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 unit. The conditioning regimen consisted of 12 Gy TBI, granulocyte colony-stimulating factor (G-CSF) plus Ara-c and CY without ATG. All patients received a combination of cyclosporine (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)×10⁷ 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) ≥ 0.5×10⁹/L was (20 ± 5) days and the average time of platelet ≥ 20×10⁹/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.

摘要

目的

回顾性分析改良清髓预处理方案(全身照射(TBI)/阿糖胞苷(Ara-c)/环磷酰胺(CY),不使用抗胸腺细胞球蛋白(ATG))的脐带血移植(UCBT)治疗成年血液系统恶性肿瘤患者的疗效。

方法

2006年9月至2011年5月,40例成年血液系统恶性肿瘤患者在单中心接受了改良清髓非血缘脐带血移植。他们的平均年龄为(23±6)岁,平均体重(58±9)kg。35例(87.5%)患者为高危患者,15例(37.5%)患者在移植前处于疾病晚期。他们接受了1份(n = 23)或2份(n = 17)脐带血单位。其中75%的患者接受了1/2人类白细胞抗原不相合单位的移植。预处理方案包括12 Gy TBI、粒细胞集落刺激因子(G-CSF)加阿糖胞苷和环磷酰胺,不使用抗胸腺细胞球蛋白。所有患者均接受环孢素(CsA)和霉酚酸酯(MMF)联合预防移植物抗宿主病(GVHD)。

结果

对于整个患者组,输注的平均细胞剂量为(4.1±1.1)×10⁷ 个有核细胞/kg和(2.4±1.0)×10⁵ 个CD34(+)细胞/kg。所有患者均获得植入,植入率为100%。绝对中性粒细胞计数(ANC)≥0.5×10⁹/L的平均时间为(20±5)天,血小板≥20×10⁹/L的平均时间为(38±12)天。23例患者(57.5%)发生急性GVHD,4例(10.0%)为Ⅲ-Ⅳ级。22.9%(8/35)可评估患者发生慢性GVHD。12.5%(5/40)的患者复发。在中位随访期19.8(范围4.6 - 55.0)个月内,移植相关死亡率在100天内为15.0%(6/40),1年内为35.0%(14/40)。主要死亡原因是肺炎和严重急性GVHD。两年总生存率(OS)和无病生存率分别为58.8%和58.8%。晚期或完全缓解疾病患者的两年OS分别为48.6%和63.8%。

结论

TBI/Ara-c/CY清髓预处理方案耐受性良好,能够在成年血液系统恶性肿瘤患者中建立持续的供体细胞植入,并降低移植相关死亡风险。对于高危和晚期患者,它可能减少复发和慢性GVHD的发生。

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