FISH检测性染色体在鉴别急性淋巴细胞白血病异基因造血干细胞移植后髓外复发与淋巴细胞增殖性疾病中的临床应用  

Identification of acute lymphoctic leukemia extramedullary relapse and PTLD after allo-HSCT by monitoring sex chromosome chimeric status with FISH

作　　者：杜璇[1] 刘启发[1] 张乐施[1] 宋兰林[1] 范志平[1] 徐兵[1] 孙竞[1] 

机构地区：[1]南方医科大学南方医院血液科,广州510515

出　　处：《中华医学遗传学杂志》2009年第2期147-150,共4页Chinese Journal of Medical Genetics

基　　金：国家“863”高技术研究发展计划基金（2006AA0224A0）,广东省自然科学基金（7005160）

摘　　要：目的 探讨荧光原位杂交（fluorescence in situ hybridization，FISH）在鉴别急性淋巴细胞白血病（acute lymphocytic leukemia，ALL）异基因造血干细胞移植（allogeneic hematopoietic stem cell transplantation，allo-HSCT）后髓外复发与移植后淋巴细胞增殖性疾病（post—transplant lymphoproliferative disease，PTLD）的可行性。方法 对6例ALL接受性别不同供者HSCT后出现淋巴结肿大或局部包块的患者，用FISH检测息者骨髓或肿瘤组织中性染色体嵌合状态和原位杂交检测肿瘤细胞内EB病毒RNA（Epstein-Barr virus，EBV—RNA）。结果6例患者骨髓细胞性染色体均示100％供者型。肿瘤组织中性染色体嵌合状态：3例受者型分别为100％、100％、98．0％，诊断白血病髓外复发；3例供者型分别为98．5％、96．0％、91．5％，诊断为PTLD。2例供者型患者EBV—RNA和EBV潜伏膜蛋白-1（latent membrane protein，LMP-1）均阳性，其他患者阴性。经治疗3例髓外复发与3例PTLD患者分别有1例部分缓解，1例完全缓解，另4例患者治疗无效死亡。结论 接受性别不同供者HSCT后出现髓外复发或PTLD的ALL患者，通过FISH检测患者肿瘤组织中性染色体嵌合状态是鉴别髓外复发与PTLD的十分有效手段。Objective To explore the role of monitoring sex chromosome chimeric status by fluorescence in situ hybridization （FISH） in the identification of leukemic extramedullary relapse and posttransplant lymphoproliferative disease （PTLD） in acute lymphocytic leukemia （ALL） after allogeneic hematopoietic stem cell transplantation （allo-HSCT）. Methods Six ALL patients who received sexmismatched allo-HSCT and manifested extravisceral lymphadenectasis or local lump were investigated. The sex chromosome chimeric status in tumor tissues and bone marrows （BM） were monitored by FISH, and EBV-RNA in the tumor tissues were detected by in situ hybridization （ISH）. Results The sex chromosomes in BM of all 6 patients were 100% donor-derived. Among the sex chromosome chimeric status of tumor tissues, three patients were mainly recipient-derived, and the percentage of sex chromosomes derived from recipients were 100%, 100% and 98.0%, respectively, and then they were diagnosed leukemic extramedullary relapse. The other 3 patients were donor-derived, the percentage was 98.5%, 96.0% and 91.5%, respectively, and were diagnosed PTLD. EBV-RNA and latent membrane protein （LMP-1） were positive in 2 patients with PTLD and negative in the other 4 patients. One patient with extramedullary relapse obtained partial remission, one with PTLD gained complete remission, and the others died eventually after therapy. Conclusion Monitoring the sex chromosome chimeric status by FISH is an effective method to distinguish leukemic extramedullary relapse from PTLD in ALL received sex-mismatched donor HSCT.

关 键 词：荧光原位杂交 急性淋巴细胞白血病 异基因造血干细胞移植 白血病髓外复发 移植后淋巴细胞增殖性疾病 

分 类 号：R686[医药卫生—骨科学]