维奈克拉联合去甲基化药物治疗母细胞性浆细胞样树突细胞肿瘤5例并文献复习

Venetoclax combined with hypomethylating agents in treatment of blastic plasmacytoid dendritic cell neoplasm: report of 5 cases and review of literature

目的探讨维奈克拉(VEN)联合去甲基化药物(HMA)治疗母细胞性浆细胞样树突细胞肿瘤(BPDCN)的效果和安全性。方法回顾性病例系列研究。收集2017年2月至2023年7月在苏州大学附属第一医院和苏州弘慈血液病医院接受VEN联合阿扎胞苷(AZA)或地西他滨(DAC)治疗的5例BPDCN患者临床资料。总结5例患者疗效、不良反应发生情况及预后。结果5例BPDCN患者均为男性,中位发病年龄[M(Q_(1),Q_(3))]为66岁(51岁,73岁),4例以皮肤病变为起病表现,1例以淋巴结大为首发表现。3例患者采用VEN联合AZA方案作为初始诱导治疗方案,其中,2例患者接受2个疗程治疗后达到血细胞计数未完全恢复的完全缓解(CRi),分别生存26.5、14.6个月病死,1例患者接受1个疗程治疗后达到部分缓解,随访3个月生存中;1例患者初始诱导治疗时采用VEN联合DAC方案,2个疗程治疗后获得存在残留皮肤异常但非活动性疾病的临床完全缓解,并接受异基因造血干细胞移植(allo-HSCT),无病生存15个月;另1例患者采用急性淋巴细胞白血病样方案联合allo-HSCT治疗后复发,接受VEN联合AZA治疗2个疗程后再次获得CRi,随访30个月无病生存中。VEN联合HMA治疗的相关血液学不良反应主要为中性粒细胞缺乏伴发热、血红蛋白减少、血小板减少,非血液学不良反应主要为恶心、呕吐等胃肠道反应;对症支持治疗后均得到改善,无治疗相关死亡事件发生。结论初诊无法耐受强化化疗方案的BPDCN患者可尝试VEN+HMA方案诱导,该方案不良反应可控,可作为allo-HSCT的桥接。

Objective:To investigate the efficacy and safety of venetoclax(VEN)combined with hypomethylating agents(HMA)in the treatment of blastic plasmacytoid dendritic cell neoplasms(BPDCN).Methods:A retrospective case series study was conducted.The clinical data of 5 patients with BPDCN treated with VEN combined with azacitidine(AZA)or decitabine(DAC)in the First Affiliated Hospital of Soochow University and Suzhou Hongci Blood Disease Hospital from February 2017 to July 2023 were collected,and the therapeutic effect,adverse reaction and prognosis of all 5 patients were summarized.Results:All 5 BPDCN patients were male with the median onset age[M(Q_(1),Q_(3))]of 66 years(51 years,73 years),of which 4 cases were presented with skin lesions and 1 case was presented with lymphadenopathy as the primary symptom.As for the treatment,3 patients were initially treated with VEN in combination with AZA induction regimen,among which 2 patients achieved complete remission with incomplete blood count recovery(CRi)after 2 cycles of treatment,survived for 26.5 months and 14.6 months,respectively and finally died,and 1 patient achieved partial remission after 1 cycle of treatment and he still survived after 3-month follow-up;1 patient was initially treated with VEN in combination with DAC induction regimen,and achieved clinical complete remission of non-active disease with residual skin abnormalities after 2 cycles of treatment followed by allogeneic hematologic stem cell transplantation(allo-HSCT)and he was in the state of disease-free survival for 15-month;and another 1 patient experienced a relapse after treatment with acute lymphocytic leukemia-like regimen in combination with allo-HSCT and again achieved CRi after 2 treatment courses of VEN in combination with AZA regimen,and he was in the state of disease-free survival for 30-month follow-up.Treatment-related haematological adverse effects of VEN combined with HMA were mainly neutropenia with fever,reduction of hemoglobin and thrombocytopenia;and non-haematological adverse effects were mainly gastrointestinal reactions such as nausea and vomiting.These adverse events improved with symptomatic supportive therapy,and no treatment-related deaths occurred.Conclusions:BPDCN patients who are unable to tolerate intensive chemotherapy regimens at initial time of diagnosis may attempt induction therapy with VEN+HMA regimen,which has a manageable adverse reaction and may serve as a bridge to allo-HSCT.