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在异基因造血干细胞移植中,经降低剂量的白消安(BUCY 2)和粒细胞集落刺激因子(G-CSF)预处理的骨髓与低移植物抗宿主病及移植相关死亡率相关。

Reduced BUCY 2 and G-CSF-primed bone marrow associates with low graft-versus-host-disease and transplant-related mortality in allogeneic HSCT.

作者信息

Leon Rodriguez Eucario, Rivera Franco Monica M, Perez Alvarez Sandra I

机构信息

Stem Cell Transplantation Program, Hematology and Oncology Department, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico.

Internal Medicine Department, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico.

出版信息

Ann Hematol. 2017 Sep;96(9):1525-1531. doi: 10.1007/s00277-017-3056-0. Epub 2017 Jul 9.

DOI:10.1007/s00277-017-3056-0
PMID:28691152
Abstract

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the ideal treatment for several diseases. However, the morbidity and mortality associated with the procedure might limit its widespread use; therefore, we implemented reduced BUCY2 as conditioning method along with the use of G-CSF-primed bone marrow (G-BM) in order to reduce complications, including graft-versus-host-disease (GVHD), and to improve survival in these patients. An analysis of transplant characteristics, complications, and survival of patients undergoing an allo-HSCT using this conditioning regimen (busulfan 12 mg/kg and cyclophosphamide 80 mg/kg) plus G-BM was performed. Forty patients were included from 1999 to 2015. All of them had a HLA-matched donor, with a median age of 32 years (range 16-59), and 55% were male. The most frequent diagnosis was myelodysplastic syndrome (MDS) in 14 patients (35%), followed by acute lymphoid leukemia (ALL) in 12 (30%). The mean of CD34+ was 2.09 × 106/kg. The mean time to neutrophil and platelet recovery was 20 and 18 days, respectively. The most common toxicity was mucositis (75%) with grade III-IV in 53% of cases. Acute GVHD appeared in 12.5 and 35% of patients developed chronic GVHD. Transplant-related mortality (TRM) was 10%. Five-year relapse-free survival was 69%, and the 5-year overall survival was 69.5%. Our conditioning method along with G-BM preserves an immunosuppressive and myeloablative effect allowing eradication of the malignant clone and achieving adequate bone marrow engraftment with acceptable toxicity, low incidence of GVHD, and low TRM, representing a favorable alternative for allo-HSCT.

摘要

异基因造血干细胞移植(allo-HSCT)是多种疾病的理想治疗方法。然而,该手术相关的发病率和死亡率可能会限制其广泛应用;因此,我们采用降低强度的BUCY2方案作为预处理方法,并联合使用粒细胞集落刺激因子动员的骨髓(G-BM),以减少并发症,包括移植物抗宿主病(GVHD),并提高这些患者的生存率。我们对采用该预处理方案(白消安12mg/kg和环磷酰胺80mg/kg)加G-BM进行allo-HSCT的患者的移植特征、并发症和生存率进行了分析。1999年至2015年共纳入40例患者。他们均有人类白细胞抗原(HLA)匹配的供者,中位年龄32岁(范围16 - 59岁),55%为男性。最常见的诊断是骨髓增生异常综合征(MDS),共14例(35%),其次是急性淋巴细胞白血病(ALL),共12例(30%)。CD34+细胞的平均数量为2.09×10⁶/kg。中性粒细胞和血小板恢复的平均时间分别为20天和18天。最常见的毒性反应是黏膜炎(75%),其中53%为III - IV级。12.5%的患者发生急性GVHD,35%的患者发生慢性GVHD。移植相关死亡率(TRM)为10%。5年无复发生存率为69%,5年总生存率为69.5%。我们的预处理方法联合G-BM保留了免疫抑制和清髓作用,能够清除恶性克隆并实现足够的骨髓植入,同时毒性可接受,GVHD发生率低,TRM低,是allo-HSCT的一种有利选择。

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