In Vitro Effect of Fludarabine, Cyclophosphamide, and Cytosine Arabinoside on Chromosome Breakage in Fanconi Anemia Patients: Relevance to Stem Cell Transplantation
In Vitro Effect of Fludarabine, Cyclophosphamide, and Cytosine Arabinoside on Chromosome Breakage in Fanconi Anemia Patients: Relevance to Stem Cell Transplantation
复制标题
氟达拉滨、环磷酰胺和阿糖胞苷对范可尼贫血患者染色体断裂的体外影响：与干细胞移植的相关性
DOI：
10.1532/ijh97.06191
复制
发表时间：
2007
影响因子：
2.1
通讯作者：
S. Kato
中科院分区：
文献类型：
--
作者：
M. Yabe;H. Yabe;S. Hamanoue;H. Inoue;M. Matsumoto;T. Koike;H. Ishiguro;T. Morimoto;S. Arakawa;Toshio Ohshima;A. Masukawa;H. Miyachi;T. Yamashita;S. Kato
由于对DNA交联剂的超敏，设计干细胞移植(SCT)治疗范可尼贫血(FA)的预适应方案已被证明是困难的。我们对56例再生障碍性贫血患者和50例患有严重再生障碍性贫血或骨髓增生异常综合征的非再生障碍性贫血患者进行了染色体脆性试验。我们评估了培养72小时的外周血淋巴细胞标本，并用丝裂霉素C、二环氧丁烷、环磷酰胺(CY)代谢物、阿糖胞苷(Ara-C)和氟达拉滨(Flu)代谢物(9-β-D-阿拉伯呋喃葡萄糖-2-氟腺嘌呤[2-F-Ara-A])处理。DEB和CY代谢物试验对FA高度敏感和特异(P<；两种试验均为10-4)，DEB和CY代谢物试验的每细胞畸变率与CY代谢物试验(P<；10-4)，但与Ara-C和2-F-Ara-A试验中每个细胞的畸变数无关。在用2-F-Ara-A处理的培养物中，FA患者和非FA患者之间的断裂频率差异无统计学意义。在2-F-Ara-A-和Ara-C处理的细胞中观察到的大多数断裂是染色单体断裂。根据体外对脆性的影响，有可能在FA患者SCT的预适应方案中确定合适的CY剂量，而对于FA患者，Flu或Ara-C可能是一种比大剂量CY更安全的条件反射药物。
Designing stem cell transplantation (SCT) conditioning regimens for Fanconi anemia (FA) has proved difficult because of hypersensitivity to the DNA cross-linking agents. We performed chromosome fragility tests with 56 FA patients and with 50 non-FA patients with severe aplastic anemia or myelodysplastic syndrome. We evaluated peripheral blood lymphocyte specimens cultured for 72 hours and treated with mitomycin C, diepoxybutane (DEB), cyclophosphamide (CY) metabolites, cytosine arabinoside (Ara-C), and fludarabine (Flu) metabolite (9-β-D-arabinofuranosyl-2-fluoroadenine [2-F-Ara-A]).The DEB and CY metabolite tests were highly sensitive and specific for FA (P < 10-4 for both tests), and the number of aberrations per cell for DEB correlated with that for the CY metabolite test (P < 10-4) but did not correlate with the number of aberrations per cell for the Ara-C and 2-F-Ara-A tests. The difference in breakage frequencies between FA and non-FA patients for cultures treated with 2-F-Ara-A was not statistically significant. Most of the breakages observed in cells treated with 2-F-Ara-A-and Ara-C were chromatid breaks. It may be possible to determine the appropriate CY dose in the preconditioning regimen for SCT in FA patients on the basis of the in vitro effects on fragility, and Flu or Ara-C may be a safer drug than high-dose CY for conditioning in FA patients.
影响因子：
20.3
作者：
Deeg, HJ;Socie, G;Storb, R
通讯作者：
Storb, R