环磷酰胺联合泼尼松治疗环孢菌素难治/复发的大颗粒淋巴细胞白血病相关纯红细胞再生障碍

杨冠群; 刘晓庆; 杨慧; 龙启强; 林圣云; 杨岩; 贾晋松; 何广胜; 李建勇

doi:10.13201/j.issn.1004-2806.2023.01.008

环磷酰胺联合泼尼松治疗环孢菌素难治/复发的大颗粒淋巴细胞白血病相关纯红细胞再生障碍

- 1.
  常熟市第一人民医院苏州大学附属常熟医院血液科(江苏常熟，215500)
- 2.
  南京市第二医院南京中医药大学附属南京医院血液科
- 3.
  江苏省人民医院南京医科大学第一附属医院血液科
- 4.
  浙江省中医院血液科
- 5.
  吉林大学第一医院血液科
- 6.
  北京大学人民医院血液科

详细信息

通讯作者: 何广胜，E-mail：heguangsheng1972@sina.com

中图分类号: R733.7

收稿日期: 2022-08-01

刊出日期: 2023-01-01

Cyclophosphamide combined with prednisolone for cyclosporine-refractory or relapsed large granular lymphocyte leukemia associated pure red cell aplasia

- 1.
  Department of Hematology, Changshu Hospital Affiliated to Soochow University, Changshu No.1 People's Hospital, Changshu, 215500, China
- 2.
  Department of Hematology, Nanjing Hospital Affiliated to Nanjing University of Traditional Chinese Medicine, the Second Hospital of Nanjing
- 3.
  Department of Hematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital
- 4.
  Department of Hematology, Zhejiang Provincial Hospital of Chinese Medicine
- 5.
  Department of Hematology, the First Hospital of Jilin University
- 6.
  Department of Hematology, Peking University People's Hospital

More Information

Corresponding author: HE Guangsheng, E-mail: heguangsheng1972@sina.com

Received Date: 01 August 2022

Publish Date: 01 January 2023

摘要

摘要: 目的评估环磷酰胺联合泼尼松(CP)方案治疗环孢菌素(CsA)难治/复发的大颗粒淋巴细胞白血病(LGLL)相关纯红细胞再生障碍(PRCA)的疗效及耐受性。方法回顾性分析登记于中国东部贫血协作组(CECGA)数据库的21例CsA治疗无效或复发的LGLL相关PRCA患者临床资料及接受CP方案治疗结果，评估疗效及耐受性。结果 CsA难治/复发患者共21例，其中难治性16例、复发性5例，经CP方案治疗后，15例达完全缓解(CR)，3例达部分缓解(PR)，3例治疗无效，治疗总有效率为85.7%(18/21)，CR率为71.4%(15/21)，中位达PR时间为2.2(0.5~6.6)个月，中位达CR时间为2.3(1.3~6.8)个月，中位疗效维持时间17.0(5.0~32.0)个月。8例STAT3突变阳性患者中7例达CR。13例(61.9%)患者在CP方案治疗期间出现不良反应，主要为粒细胞减少和肝功能异常，2例患者因4级粒细胞减少停药。随访期内，无治疗相关死亡事件。3例(14.3%)患者因药物减停出现复发。中位随访20.0(4.0~34.0)个月，15例仍有效，中位无复发生存时间为16.0(3.0~32.0)个月。结论对于CsA难治/复发的LGLL相关PRCA患者，CP方案疗效确切，且对STAT3突变阳性患者也效果良好。CP方案主要不良反应为骨髓毒性。
- 大颗粒淋巴细胞白血病 /
- 纯红细胞再生障碍 /
- 环孢菌素 /
- 难治 /
- 复发 /
- 环磷酰胺
Abstract: Objective To investigate the efficacy and tolerance of cyclophosphamide combined with prednisolone(CP) for the treatment of patients with large granular lymphocyte leukemia(LGLL) associated pure red cell aplasia(PRCA), refractory to or relapsed after cyclosporine (CsA) treatment.Methods Clinical data of 21 LGLL-associated PRCA patients who get failure to CsA therapy from June 2019 to June 2022 in the China Eastern Cooperation Group for Anemia(CECGA) were analyzed. The treatment outcomes and tolerability of CP regimen were evaluated.Results Among the 21 patients, 16 cases were refractory to CsA and 5 cases relapsed. All patients were then treated with CP regimen. The overall response rate was 85.7%(18/21), including 15 cases with complete response(CR) and 3 cases with partial response(PR). The median time to achieve PR and CR was 2.2(0.5-6.6) months and 2.3(1.3-6.8) months, respectively. The median response duration time was 17.0(5.0-32.0) months. Eight cases occurred STAT3 mutations and 7 of them achieved CR after CP treatment. Thirteen patients(61.9%) had adverse events during CP therapy, mainly including neutropenia and hepatotoxicity. Two patients discontinued cyclophosphamide due to agranulocytosis(grade 4). No treatment-related death was occurred during the follow-up. Three patients relapsed after reduction or discontinuation of cyclophosphamide. After a median follow-up of 20.0(4.0-34.0) months, 15 patients maintained stable response with a median relapse-free survival time of 16.0(3.0-32.0) months.Conclusion For LGLL-associated PRCA patients refractory to or relapsed after CsA treatment, CP regimen is effective. And patients with STAT3 mutation have good response. Myelosupression is the main adverse event during CP treatment.
- large granular lymphocyte leukemia /
- pure red cell aplasia /
- cyclosporine /
- refractory /
- relapse /
- cyclophosphamide

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图 1 LGLL相关PRCA患者CP方案疗效曲线

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表 1 CsA难治/复发的LGLL相关PRCA临床特征中位数(范围)

临床特征	数值
性别(男/女)/例	10/11
年龄/岁	54.0(22.0~81.0)
病程/月	52.0(8.0~141.0)
T/NK/例	21/0
中性粒细胞计数/(×10⁹·L^-1)	1.2(0.4~4.6)
淋巴细胞比例/%	64.1(4.8~90.0)
血红蛋白/(g·L^-1)	71.0(31.0~99.0)
血清乳酸脱氢酶/(U·L^-1)	225.0(125.0~341.0)
血清β2-微球蛋白/(mg·L^-1)	2.6(1.6~5.0)
血清铁蛋白/(ng·mL^-1)	589.1(42.8~1 441.9)
STAT3突变(+/-)/例	8/13
TCR重排(+/-)/例	19/2
CD3⁺CD4⁺细胞比例/%	17.0(7.3~57.3)
CD3⁺CD8⁺细胞比例/%	70.0(20.2~89.5)
CD4/CD8	0.2(0.1~2.9)
CD57⁺细胞比例/%	21.0(5.4~42.0)

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