%0 Case Reports
%T [Ibrutinib combined with CAR-T cells in the treatment of del (17p) chronic lymphocytic leukemia with BCL-2 inhibitor resistance: a case report and literature review].
%A Gong JJ
%A Yin QS
%A Li MJ
%A Ai H
%A Wang Q
%A Chen L
%A Wei XD
%A Song YP
%J Zhonghua Xue Ye Xue Za Zhi
%V 40
%N 9
%D Sep 2019 14
%M 31648477
暂无%R 10.3760/cma.j.issn.0253-2727.2019.09.008
%X Objective: To improve the knowledge and experience of ibrutinib combined with CAR-T cells in the treatment of high-risk chronic lymphoblastic leukemia (CLL) patients or small lymphocytic lymphoma (SLL) with TP53 gene aberration. Methods: One case of del (17p) CLL patients with BCL-2 inhibitor resistance was treated with ibrutinib combined with CAR-T cells, successfully bridged to allogeneic hematopoietic stem cell transplantation (allo-HSCT) , and the relative literatures were reviewed. Results: The patient was a young female with superficial lymph node enlarging at the beginning of the onset. Lymph node biopsy was confirmed as small lymphocytic lymphoma (SLL) without del (17p) . The disease progressed rapidly to CLL/SLL with del (17p) and bone marrow hematopoietic failure 2 years later. Firstly, the patient was treated with BCL-2 inhibitor (Venetoclax) , and the enlarged lymph nodes shrank significantly 2 months later. After 3 months, the disease progressed rapidly. The spleen was enlarged to 16 cm below the ribs, the neck lymph nodes was rapidly enlarged, and the superior vena cava syndrome appeared, which were mainly attributed to venetoclax resistance; so BTK inhibitor (ibrutinib) was used continuously after venetoclax discontinuation. Partial remission (PR) was achieved without lymphocytosis after 2 months, then ibrutinib was combined with CAR-T cells targeting CD19 antigen. Grade 1 of cytokine release syndrome (CRS) appeared after CAR-T cells infusion, and the complete remission (CR) was achieved after 1 month both in bone marrow and peripheral blood, with minimal residual disease (MRD) negative, then bridging allo-HSCT after 2 months of combined therapy. Conclusion: CLL/SLL patients with TP53 aberration have poor prognosis because of rapid progression, drug resistance, etc. Ibrutinib combined with CAR-T cell therapy can quickly achieved complete remission.<BR>目的： 总结伊布替尼联合嵌合抗原受体T细胞（CAR-T）治疗TP53基因异常超高危慢性淋巴细胞白血病（CLL）/小细胞淋巴瘤（SLL）的经验，提高对此类疾病的认识。 方法： 报告1例伴del（17p）CLL/SLL患者BCL-2抑制剂耐药后，采用伊布替尼联合CAR-T成功治疗并顺利桥接异基因造血干细胞移植（allo-HSCT）的治疗经过，并进行文献复习。 结果： 患者为年轻女性，发病初表现为全身浅表淋巴结肿大，淋巴结活检病理确诊为SLL，无del（17p）；2年后疾病快速进展为CLL/SLL，伴del（17p），骨髓造血衰竭。采用BCL-2抑制剂维奈托克治疗2个月余肿大淋巴结明显缩小，3个月后疾病快速进展，脾脏增大至肋缘下16 cm，颈部淋巴结增大融合，并出现上腔静脉压迫综合征，考虑维奈托克耐药；遂更换为BTK抑制剂伊布替尼治疗，2个月余疾病达部分缓解（PR），联合靶向CD19的CAR-T治疗，细胞因子释放综合征（CRS）1级，1个月后达骨髓及外周血完全缓解（CR），且微小残留病（MRD）阴性，2个月后桥接allo-HSCT。 结论： TP53基因异常CLL/SLL临床进展快、易耐药、预后差，伊布替尼联合CAR-T治疗可快速达CR。.