The therapeutic effect of hematopoietic stem cell transplantation and cell therapy for blastic plasmacytoid dendritic cell neoplasm
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摘要: 目的 探讨不同治疗方式对于母细胞性浆细胞样树突细胞肿瘤(BPDCN)患者的临床疗效及安全性。方法 回顾性分析2015年7月—2021年6月苏州大学附属第一医院收治的6例BPDCN患者的临床资料。结果 所有患者均以皮肤或淋巴结受累起病，部分累及骨髓(5例)、外周血(5例)、脾(1例)、鼻咽部(1例)。所有患者为CD4、CD56双阳性表达，1例出现染色体易位，2例伴分子生物学改变。5例采用化疗桥接异基因造血干细胞移植，其中2例复发；1例给予去甲基化联合BCL-2靶向治疗后复发。3例复发患者中2例采用挽救性嵌合抗原受体T细胞疗法，均因疾病进展死亡；1例给予靶向药物维奈托克联合阿扎胞苷、供者淋巴细胞输注、干扰素注射、局部放疗后缓解。1例死于感染。总生存率50.0%(3/6)，中位随访25.5(7.0~72.2)个月，中位无进展生存期8.9个月，中位总生存期25.5个月。结论 BPDCN总体预后不良，建立预后分层模型可能有助于治疗方案选择。化疗桥接异基因造血干细胞移植仍是目前有效的治疗手段且安全性良好，靶向及免疫治疗疗效需进一步验证及改善。
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关键词:
- 母细胞性浆细胞样树突细胞肿瘤 /
- 异基因造血干细胞移植 /
- 嵌合抗原受体T细胞疗法 /
- 预后
Abstract: Objective To explore the therapeutic outcomes and safety of different treatments in blastic plasmacytoid dendritic cell neoplasm(BPDCN).Methods We retrospectively analyzed clinical data at diagnosis and treatment results of 6 patients with BPDCN admitted to the First Affiliated Hospital of Soochow University from July 2015 to June 2021.Results All six patients had initial skin lesion or lymphadenectasis, with 5 cases involving bone marrow, 5 cases involving peripheral blood, 1 case involving spleen and 1 case involving nasopharynx. All patients were double positive for CD4 and CD56, and 1 case had chromosomal translocation, 2 cases had molecular biological change. Two of five cases relapsed after chemotherapy bridging allogeneic hematopoietic stem cell transplantation(allo-HSCT), and 1 case relapsed after demethylation combined with BCL-2 targeted therapy. Of the 3 patients with recurrence, 2 cases treated with salvage chimeric antigen receptor T cell therapy and both died due to disease progression. The other one achieved remission from targeted drug of venetoclax and azacitidine, donor lymphocyte infusion, interferon, local radiotherapy. On the other hand, 1 case died of infection. The overall survival rate was 50.0%(3/6). The median follow-up duration was 25.5(7.0-72.2) months, the median progression-free survival was 8.9 months, and the median overall survival was 25.5 months.Conclusion The overall prognosis of BPDCN is poor. A prognostic stratification model may be helpful for the selection of therapy strategies. Chemotherapy bridging allo-HSCT remains an effective therapy with satisfactory safety at present, and the efficacy of targeted and immunotherapy needs to be further verified and improved. -
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表 1 6例患者的免疫表型
病例 CD4 CD56 CD123 CD303 CD304 CD38 HLA-DR TdT CD3 CD79a MPO Ki-67/% 1 + + + NA NA NA NA NA NA NA NA 30~40 2 局灶 + - NA NA NA NA - - - - 75~80 3 + + NA NA NA NA NA NA - 局灶 NA 85 4 + + + + NA + + + - - - NA 5 + + + + + 局灶 + NA - - - 50~60 6 + + + NA NA + NA - - - - 95 TdT：末端脱氧核苷酸转移酶；MPO：髓过氧化物酶；NA：未检测或资料缺失。 
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表 2 6例患者的治疗及转归
特征 病例1 病例2 病例3 病例4 病例5 病例6 首次治疗 ALL型化疗 ALL型化疗+鞘注 ALL型化疗 ALL型化疗+鞘注 NHL型化疗 去甲基化+靶向治疗 治疗反应 CR1 CR1 CR1 CR1 CR1 CR1 移植预处理方案 改良Bu/Cy+ATG 改良Bu/Cy+ATG 改良Bu/Cy 改良Bu/Cy+ATG 改良Bu/Cy+ATG 不适用 移植时间△/月 7.5 3.6 5.1 4.4 4.6 不适用 供体类型 亲缘半相合 亲缘半相合 亲缘全相合 亲缘半相合 亲缘半相合 不适用 干细胞来源 骨髓+外周血 骨髓+外周血 骨髓+外周血 骨髓+外周血 外周血 不适用 移植物植入 是 是 是 是 是 不适用 GVHD 无 急性+慢性 慢性 无 急性 不适用 复发时间▲/月 无复发 10.8 无复发 4.1 无复发 4.9 复发累及部位 不适用 皮肤 不适用 淋巴结+脾+骨髓+中枢(可疑) 不适用 皮肤+骨髓 复发后治疗 不适用 靶向+去甲基化，DLI，干扰素，放疗 不适用 化疗，干扰素，DLI，CAR-T 不适用 靶向+去甲基化，CAR-T 转归 无病生存 无病生存 死于感染 死于复发 无病生存 死于复发 随访时间△/月 72.2 55.7 36.4 14.6 7.0 14.6 △距疾病确诊时间；▲距前次治疗结束时间。
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表 3 2例复发患者的CAR-T细胞治疗情况
病例 CAR-T细胞治疗前状态 预处理方案 CAR-T细胞靶标 CAR-T细胞数/(×106·kg-1) 疗效 持续时间/月 CRS 等级 处理 转归 4 未缓解 地西他滨+氟达拉滨+环磷酰胺 CD123 2.00 部分缓解 1.8 Ⅱ级 对症 好转 6 部分缓解 氟达拉滨+环磷酰胺 CD123+CD38 0.84+1.30 进展 不适用 0级 不适用 不适用
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