Department of Leukemia and.
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX.
Blood Adv. 2019 Mar 26;3(6):922-933. doi: 10.1182/bloodadvances.2018026989.
Nucleophosmin () mutations are common in acute myeloid leukemia and are associated with high remission rates and prolonged survival with intensive chemotherapy. mutations are rare in myelodysplastic syndromes (MDS) or myelodysplastic/myeloproliferative neoplasm (MDS/MPN), and the clinical outcomes of these patients, when treated with intensive chemotherapy, are unknown. We retrospectively evaluated the clinicopathologic characteristics and the impact of therapy in 31 patients with MDS or MDS/MPN and mutations. Next-generation sequencing was performed at diagnosis in 22 patients. Median age was 62 years (range, 19-86). Twenty-four patients (77%) had normal karyotype, and all had multilineage dysplasia. Most patients could be classified as MDS with excess blasts (19/31, 61%). mutations were detected at a median allele frequency of 0.38 (range, 0.09-0.49). Mutation burden did not correlate with bone marrow blast frequency, and its clearance seemed to be associated with decreased morphologic dysplasia. Ten of the 31 patients (32%) received cytotoxic chemotherapy, 20 (65%) hypomethylating agents, and 1 (4%) lenalidomide. Sequential sequencing was available in 16 (52%) patients, and mutation burden correlated with disease status and response to therapy. Patients treated with chemotherapy had higher complete response rates (90% vs 28%, = .004), longer median progression-free survival (not reached vs 7.5 months, = .023), and overall survival (not reached vs 16 months, = .047). Intensive chemotherapy and allogeneic stem cell transplantation (SCT) may be associated with improved clinical outcomes in patients with -mutated MDS or MDS/MPN who are candidates for this form of therapy.
核仁磷酸蛋白（）突变在急性髓系白血病中很常见，与强化化疗后的高缓解率和延长生存时间相关。在骨髓增生异常综合征（MDS）或骨髓增生异常/骨髓增殖性肿瘤（MDS/MPN）中，突变很少见，这些患者接受强化化疗的临床结局尚不清楚。我们回顾性评估了 31 例 MDS 或 MDS/MPN 伴 突变患者的临床病理特征和治疗影响。22 例患者在诊断时进行了下一代测序。中位年龄为 62 岁（范围 19-86 岁）。24 例（77%）患者核型正常，均有多系发育不良。大多数患者可归类为伴原始细胞增多的 MDS（19/31，61%）。在中位等位基因频率为 0.38（范围 0.09-0.49）时检测到 突变。突变负荷与骨髓原始细胞频率无关，其清除似乎与形态学发育不良减少相关。31 例患者中有 10 例（32%）接受细胞毒性化疗，20 例（65%）接受低甲基化药物治疗，1 例（4%）接受来那度胺治疗。16 例（52%）患者可进行序贯测序，突变负荷与疾病状态和治疗反应相关。接受化疗的患者完全缓解率更高（90%比 28%，=0.004），无进展生存期更长（未达到比 7.5 个月，=0.023），总生存期更长（未达到比 16 个月，=0.047）。对于适合这种治疗形式的伴有 突变的 MDS 或 MDS/MPN 患者，强化化疗和异基因造血干细胞移植（SCT）可能与改善临床结局相关。
