Clinical features and outcomes of patients with Shwachman-Diamond syndrome and myelodysplastic syndrome or acute myeloid leukaemia: a multicentre, retrospective, cohort study.
Clinical features and outcomes of patients with Shwachman-Diamond syndrome and myelodysplastic syndrome or acute myeloid leukaemia: a multicentre, retrospective, cohort study.
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Shwachman-Diamond综合征和骨髓增生性综合征或急性髓样白血病患者的临床特征和结果：多中心，回顾性，队列研究。
DOI：
10.1016/s2352-3026(19)30206-6
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发表时间：
2020-03
期刊：
影响因子：
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通讯作者：
Shimamura A
中科院分区：
文献类型：
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作者：
Myers KC;Furutani E;Weller E;Siegele B;Galvin A;Arsenault V;Alter BP;Boulad F;Bueso-Ramos C;Burroughs L;Castillo P;Connelly J;Davies SM;DiNardo CD;Hanif I;Ho RH;Karras N;Manalang M;McReynolds LJ;Nakano TA;Nalepa G;Norkin M;Oberley MJ;Orgel E;Pastore YD;Rosenthal J;Walkovich K;Larson J;Malsch M;Elghetany MT;Fleming MD;Shimamura A
白血病易感综合征的监测和治疗数据有限，建议主要基于专家意见。本研究旨在探讨骨髓增生异常综合征和急性髓系白血病在Shwachman Diamond综合征中的临床特征和结局，Shwachman Diamond综合征是一种具有高骨髓恶性肿瘤风险的遗传性骨髓衰竭疾病。我们在美国和加拿大的17个中心进行了一项多中心、回顾性队列研究。发生骨髓增生异常综合征或急性髓性白血病的Shwachman Diamond综合征遗传或临床诊断患者符合条件，无额外限制。审查了36例患者2001年3月1日至2017年10月5日的病历。在27例可用病例中进行了骨髓病理学的盲态中心审查。进行临床特征描述和生存评估。中位随访时间为4.9年（范围：0.3-10.1，IQR：3.9-8.4）。中位年龄为18岁（范围：0.5-47.0，IQR：10-24）。56%（n=15/27）的中心病理学审查与当地诊断一致。治疗是异质性的10个化疗方案和16个造血干细胞移植方案。最初接受化疗的10例白血病患者中只有1例达到完全缓解。白血病患者骨髓增生异常综合征/白血病诊断的中位生存期为0.99年（95% CI：0.2-2.4，IQR：0.6-1.1），骨髓增生异常综合征患者为7.7年（95% CI：0.8-NA; IQR：0.7-NA）。白血病和骨髓增生异常综合征的3年总生存率分别为11%（95% CI：1-39，n=10）和51%（95% CI：29-68，n=26）。在33%（n=3/9）的白血病和46%（n=11/24）的骨髓增生异常综合征受试者中进行了骨髓监测。在骨髓增生异常综合征/白血病诊断前接受骨髓监测的个体3年OS为62%（95% CI：32-82，n=14），而未接受监测的个体为28%（95% CI：10-50，n=19）（p= 0.13）。几名患者在血细胞计数稳定的情况下发生骨髓增生异常综合征（n=6）。由于治疗抵抗性疾病和治疗相关毒性，Shwachman Diamond综合征白血病患者的预后很差。需要改进早期疾病检测/风险分层的监测算法，克隆进化的生物学研究和前瞻性临床试验，以告知白血病易感性的有效预防和治疗策略。
Data to inform surveillance and treatment for leukemia predisposition syndromes are limited and recommendations largely based on expert opinion. This study aimed to investigate the clinical features and outcomes of myelodysplastic syndrome and acute myeloid leukemia in Shwachman Diamond syndrome, an inherited marrow failure disorder with high risk of myeloid malignancy. We performed a multicentre, retrospective cohort study in 17 centres in the USA and Canada. Patients with a genetic or clinical diagnosis of Shwachman Diamond syndrome who developed myelodysplastic syndrome or acute myeloid leukemia were eligible without additional restriction. Medical records from March 1, 2001 to October 5, 2017 were reviewed for 36 patients. Blinded central review of bone marrow pathology was performed in 27 available cases. Description of clinical features and survival assessment was performed. Median follow-up was 4·9 years (range: 0.3–10.1, IQR: 3.9–8.4). Median age was 18 years (range: 0.5–47.0, IQR:10–24). Central pathology review concurred with local diagnosis in 56% (n=15/27). Treatment was heterogeneous with 10 chemotherapy regimens and 16 hematopoietic stem cell transplant regimens. Only 1 of 10 initially treated with chemotherapy for leukemia achieved complete remission. Median survival from myelodysplastic syndrome / leukemia diagnosis was 0·99 years in leukemia (95% CI: 0.2–2.4, IQR: 0.6–1.1) and 7·7 years in myelodysplastic syndrome (95% CI: 0.8-NA; IQR: 0.7-NA). Overall survival at 3 years was 11% (95% CI:1–39, n=10) and 51% (95% CI:29–68, n=26) for leukemia and myelodysplastic syndrome respectively. Bone marrow surveillance was conducted in 33% (n=3/9) of leukemia and 46% (n=11/24) of myelodysplastic syndrome subjects. Individuals monitored with bone marrow surveillance prior to myelodysplastic syndrome / leukemia diagnosis had a 3-year OS of 62% (95% CI: 32–82, n=14) compared with 28% without surveillance (95% CI:10–50, n=19) (p=0·13). Several patients developed myelodysplastic syndrome in the setting of stable blood counts (n=6). Prognosis is poor for Shwachman Diamond syndrome patients with leukemia due to both therapy-resistant disease and treatment-related toxicities. Improved surveillance algorithms for early disease detection/risk stratification, biological studies of clonal evolution and prospective clinical trials are needed to inform effective prevention and treatment strategies for leukemia predisposition.