Forester Craig M, Sartain Sarah E, Guo Dongjing, Harris Marian H, Weinberg Olga K, Fleming Mark D, London Wendy B, Williams David A, Hofmann Inga
Department of Pediatrics, Boston Children's Hospital, Boston, Massachusetts.
Am J Hematol. 2015 Apr;90(4):320-6. doi: 10.1002/ajh.23937. Epub 2015 Mar 2.
Pediatric acquired aplastic anemia (AA) is a bone marrow disorder that is difficult to distinguish from inherited bone marrow failure syndromes and hypocellular refractory cytopenia of childhood (RCC). Historically, patients with hypocellular RCC have been given the diagnosis of AA. To assess the clinical and histologic distinction between RCC and AA, we performed a retrospective analysis of 149 patients previously diagnosed with AA between 1976 and 2010. We evaluated event free survival (EFS), overall survival (OS), response rates to immunosuppressive therapy, treatment-related toxicities and clonal evolution. The 5-year EFS and OS were 50.8% ± 5.5% and 73.1% ± 4.7%, respectively. Patients with very severe AA had worse OS compared to patients with severe and moderately severe AA. Seventy-two patients had diagnostic pathology specimens available for review. Three pediatric hematopathologists reviewed and reclassified these specimens as AA, RCC or Other based on 2008 WHO Criteria. The concordance between pathologists in the diagnosis of AA or RCC was modest. RCC was associated with a trend toward improved OS and EFS and was not prognostic of immunosuppression therapy treatment failure. There was a low rate of clonal evolution exclusively associated with moderately severe AA. Our findings indicate that a diagnosis of RCC is difficult to establish with certainty and does not predict outcomes, calling into question the reproducibility and clinical significance of the RCC classification and warranting further studies.
儿童获得性再生障碍性贫血（AA）是一种骨髓疾病，难以与遗传性骨髓衰竭综合征及儿童低细胞难治性血细胞减少症（RCC）相区分。从历史上看，低细胞RCC患者一直被诊断为AA。为评估RCC与AA之间的临床和组织学差异，我们对1976年至2010年间149例先前诊断为AA的患者进行了回顾性分析。我们评估了无事件生存期（EFS）、总生存期（OS）、免疫抑制治疗的缓解率、治疗相关毒性及克隆演变情况。5年EFS和OS分别为50.8%±5.5%和73.1%±4.7%。与重度和中度重度AA患者相比，极重度AA患者的OS更差。72例患者有可供复查的诊断性病理标本。三位儿科血液病理学家根据2008年世界卫生组织标准对这些标本进行复查并重新分类为AA、RCC或其他类型。病理学家在AA或RCC诊断方面的一致性一般。RCC与OS和EFS改善趋势相关，且不是免疫抑制治疗失败的预后指标。仅与中度重度AA相关的克隆演变发生率较低。我们的研究结果表明，RCC的诊断难以确切确立，且无法预测预后，这对RCC分类的可重复性和临床意义提出了质疑，需要进一步研究。
