Maciejewski Jaroslaw P, Risitano Antonio, Sloand Elaine M, Nunez Olga, Young Neal S
Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Blood. 2002 May 1;99(9):3129-35. doi: 10.1182/blood.v99.9.3129.
A serious complication of aplastic anemia (AA) is its evolution to clonal hematologic diseases such as myelodysplasia (MDS) and leukemia, which is usually associated with the appearance of a cytogenetic abnormality in bone marrow cells. We present here an analysis of a cohort of 30 patients with otherwise typical AA in whom clonal karyotypic evolution was observed during frequent periodic marrow examinations. The actuarial risk for this complication has been estimated in other studies at around 15% at 5 years. Conversion from normal to abnormal karyotype occurred at a constant rate after initial diagnosis, with about 50% of cases developing within the first 30 months. Transient chromosomal abnormalities were infrequent. Clinically, AA patients with clonal cytogenetic patterns were heterogenous; a variety of karyotypic defects with numerical and structural abnormalities of chromosome 7 accounted for 40% of all cases followed by trisomy 8, structural and numerical abnormalities of chromosome 13, deletion of Y chromosome, and complex cytogenetic abnormalities. Unlike in primary MDS, aberrancies of chromosome 5 and 20 were infrequent. The clinical course depended on the specific abnormal cytogenetic pattern. Most deaths related to leukemic transformation occurred in patients with abnormalities of chromosome 7 or complex cytogenetic alterations or both. Evolution of chromosome 7 abnormalities was seen most often in refractory patients who had failed to respond to therapy. In contrast, trisomy 8 developed in patients with good hematologic responses who often required chronic immunosuppression with cyclosporine A (CsA), and survival was excellent. Although AA patients with monosomy 7 showed a similar prognosis to those with primary MDS, trisomy 8 in AA appears to have a more favorable prognosis than in MDS.
再生障碍性贫血（AA）的一个严重并发症是其演变为克隆性血液系统疾病，如骨髓增生异常综合征（MDS）和白血病，这通常与骨髓细胞中细胞遗传学异常的出现有关。我们在此呈现对一组30例典型AA患者的分析，这些患者在频繁的定期骨髓检查期间观察到克隆性核型演变。在其他研究中，估计这种并发症在5年时的精算风险约为15%。初始诊断后，从正常核型转变为异常核型的发生率恒定，约50%的病例在最初30个月内发生。短暂性染色体异常并不常见。临床上，具有克隆性细胞遗传学模式的AA患者具有异质性；各种核型缺陷，包括7号染色体的数量和结构异常，占所有病例的40%，其次是8号染色体三体、13号染色体的结构和数量异常、Y染色体缺失以及复杂的细胞遗传学异常。与原发性MDS不同，5号和20号染色体异常并不常见。临床病程取决于特定的异常细胞遗传学模式。大多数与白血病转化相关的死亡发生在具有7号染色体异常或复杂细胞遗传学改变或两者皆有的患者中。7号染色体异常的演变最常见于对治疗无反应的难治性患者。相比之下，8号染色体三体发生在血液学反应良好的患者中，这些患者通常需要用环孢素A（CsA）进行慢性免疫抑制，且生存率极佳。虽然7号染色体单体的AA患者与原发性MDS患者的预后相似，但AA中的8号染色体三体似乎比MDS具有更有利的预后。
