Allogeneic hematopoietic stem cell transplantation for acute B-lymphoblastic leukemia in TEL-AML1-positive adolescents and young adults: 4 cases report and literature review
-
摘要: 目的 TEL-AML1阳性青少年及年轻成人(AYA)急性B淋巴细胞白血病(B-ALL)的临床特征及造血干细胞移植治疗效果尚不明确，本研究总结4例患者的临床特征及异基因造血干细胞移植治疗预后并复习相关文献。方法 回顾性报道我中心4例接受异基因造血干细胞移植的TEL-AML1阳性AYA患者，分析其临床特征及预后。结果 4例患者中位年龄16.5岁(15~33岁)，免疫表型均为B-ALL，经1~2个疗程诱导化疗后达完全缓解，后接受异基因造血干细胞移植治疗，其中2例移植前接受自体嵌合抗原受体T(CAR-T)细胞治疗，1例随访18个月持续无病生存，另1例移植后复发再次给予供体来源CD19 CAR-T治疗后达完全缓解。4例患者中位随访时间38个月(13.3~74.6个月)，均完全缓解状态存活。结论 TEL-AML1阳性AYA患者对化疗敏感，但预后存在异质性。CAR-T细胞治疗是难治复发TEL-AML1阳性AYA B-ALL患者的有效治疗手段，微小残留病指导下的异基因造血干细胞移植或可提高该类患者的总体生存。
-
关键词:
- 急性B淋巴细胞白血病 /
- 青少年及年轻成人 /
- TEL-AML1 /
- CAR-T /
- 异基因造血干细胞移植
Abstract: Objective The clinical characteristics and effect of allogeneic hematopoietic stem cell transplantation(allo-HSCT) in TEL-AML1-positive adolescents and young adults(AYA) patients with B-cell acute lymphoblastic leukemia(B-ALL) remain unclear. This study summarized the clinical features and experience of allo-HSCT in 4 cases, and reviewed the relevant literatures.Methods Four TEL-AML1-positive AYA patients in our center who received allo-HSCT were retrospectively collected, and their clinical characteristics and prognosis were reported.Results The median age of 4 patients was 16.5 years(15-33 years) and the immunophenotype of these patients were B-ALL. All of them achieved complete remission after 1-2 courses of induction chemotherapy. Moreover, they were all received allo-HSCT. Two patients received autologous chimeric antigen receptor T-cell(CAR-T) therapy before transplantation, and one case remained sustained disease-free survival during the follow-up(18 months), the other one relapsed after transplantation and achieved complete remission after donor-derived CD19 CAR-T therapy. Four patients were followed up for 38 months(range 13.3-74.6 months) and they were all survived with complete remission.Conclusion TEL-AML1-positive AYA patients are sensitive to chemotherapy, while there is heterogeneity in prognosis. CAR-T therapy is an effective treatment method for patients with refractory recurrent TEL-AML1-positive AYA B-ALL. Allo-HSCT monitored by minimal residual disease might improve the overall survival of these patients. -
-
表 1 4例TEL-AML1阳性AYA B-ALL患者的初诊基本信息
病例 性别 年龄/岁 外周血原始细胞/% WBC/(×109·L-1) Hb/(g·L-1) PLT/(×109·L-1) 骨髓原始细胞/% 免疫表型 细胞遗传学 基因突变 TEL-AML1拷贝数/(copies/10 000 abl copies) 1 男 15 80 2.76 92 134 91.0 B(CD34/CD10/ CD19/CD13/CD79a) (-) (-) 5136 2 男 16 59 6.13 88 30 95.0 B(CD19/CD10/ CD34，CD45，CD38，CD22，CD81) (-) NRAS，DDX3X，EZH2，JAK1突变 766 3 女 17 70 6.50 63 126 77.0 B(CD10/CD34/ CD19/CD13/CD79a) 复杂核型△ BCOR基因J103A突变 9572 4 女 33 80 5.02 78 13 90.5 B(CD10/CD19/ CD13/CD33/CD34/ CD81) (-) (-) 10 923 △复杂核型为84-90，XXXX，-2，2p+，-3，-4，-4，-6，-6，-6，-7，-7，-8，-8，+9，+9，+？10，+11，-12，12p+，12p+，+14，14q-，14q-，-15，-16，+17，+18，-19，-20，-20，+22，+M×1-4[cp7]。 
下载: 导出CSV
-
[1] 蔡玉丽, 邹尧, 陈晓娟, 等. 982例儿童急性淋巴细胞白血病流行病学研究[J]. 中国实验血液学杂志, 2020, 28(2): 371-376. https://www.cnki.com.cn/Article/CJFDTOTAL-XYSY202002008.htm
[2] 郑湧智, 潘丽丽, 李健, 等. ETV6-RUNX1融合基因阳性儿童急性前体B淋巴细胞白血病的临床特征及预后分析[J]. 中华血液学杂志, 2021, 42(1): 45-51.
[3] Jawdat D, Almashaqbeh W, Sumaily A, et al. Screening for pre-leukemia TEL-AML1 chromosomal translocation in banked cord blood units: cord blood bank perspective[J]. Cell Tissue Bank, 2020, 21(4): 625-630. doi: 10.1007/s10561-020-09855-y
[4] 闫梦, 吴艳珺, 陈峰, 等. CAR-T细胞桥接异基因造血干细胞移植治疗复发/难治急性B淋巴细胞白血病的临床分析[J]. 中华血液学杂志, 2020, 41(9): 710-715.
[5] Xu LS, Francis A, Turkistany S, et al. ETV6-RUNX1 interacts with a region in SPIB intron 1 to regulate gene expression in pre-B-cell acute lymphoblastic leukemia[J]. Exp Hematol, 2019, 73: 50-63. e2. doi: 10.1016/j.exphem.2019.03.004
[6] Gupta DG, Varma N, Naseem S, et al. Characterization of the immunophenotypic aberrancies with respect to common fusion transcripts in B-cell precursor acute lymphoblastic leukaemia-a report of 986 Indian patients[J]. Turk J Haematol, 2022, 39(1): 1-12. doi: 10.4274/tjh.galenos.2021.2021.0326
[7] Mattano LA Jr, Devidas M, Maloney KW, et al. Favorable Trisomies and ETV6-RUNX1 Predict Cure in Low-Risk B-Cell Acute Lymphoblastic Leukemia: Results From Children's Oncology Group Trial AALL0331[J]. J Clin Oncol, 2021, 39(14): 1540-1552. doi: 10.1200/JCO.20.02370
[8] Derwich K, Brzezinski A, Karpenko C, et al. Acute Lymphoblastic Leukemia in Adolescents and Young Adults: A Polish Perspective[J]. J Adolesc Young Adult Oncol, 2022, 11(1): 1-5. doi: 10.1089/jayao.2021.0033
[9] Polak R, Bierings MB, van der Leije CS, et al. Autophagy inhibition as a potential future targeted therapy for ETV6-RUNX1-driven B-cell precursor acute lymphoblastic leukemia[J]. Haematologica, 2019, 104(4): 738-748. doi: 10.3324/haematol.2018.193631
[10] Stock W, Luger SM, Advani AS, et al. A pediatric regimen for older adolescents and young adults with acute lymphoblastic leukemia: results of CALGB 10403[J]. Blood, 2019, 133(14): 1548-1559. doi: 10.1182/blood-2018-10-881961
[11] Brudno JN, Kochenderfer JN. Recent advances in CAR T-cell toxicity: Mechanisms, manifestations and management[J]. Blood Rev, 2019, 34: 45-55. doi: 10.1016/j.blre.2018.11.002
[12] 熊润稷, 张冰玉, 金润铭. 嵌合抗原受体T细胞治疗儿童急性B淋巴细胞白血病的研究进展[J]. 临床血液学杂志, 2021, 34(11): 825-828, 832. https://www.cnki.com.cn/Article/CJFDTOTAL-LCXZ202111016.htm
[13] Maude SL, Laetsch TW, Buechner J, et al. Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia[J]. N Engl J Med, 2018, 378(5): 439-448. doi: 10.1056/NEJMoa1709866
[14] Park JH, Rivière I, Gonen M, et al. Long-Term Follow-up of CD19 CAR Therapy in Acute Lymphoblastic Leukemia[J]. N Engl J Med, 2018, 378(5): 449-459. doi: 10.1056/NEJMoa1709919
[15] 左英熹, 王静波, 陆爱东, 等. 嵌合抗原受体T细胞治疗儿童急性B淋巴细胞白血病异基因造血干细胞移植后复发一例报告并文献复习[J]. 中华血液学杂志, 2016, 37(2): 115-118. https://www.cnki.com.cn/Article/CJFDTOTAL-XDKF201933006.htm
[16] 赵艳丽, 陆佩华. CAR-T细胞治疗在急性B细胞淋巴细胞白血病异基因造血干细胞移植中的应用[J]. 临床血液学杂志, 2021, 34(9): 603-607. https://www.cnki.com.cn/Article/CJFDTOTAL-LCXZ202109001.htm
[17] Lee JW, Kim S, Jang PS, et al. Differing Outcomes of Patients with High Hyperdiploidy and ETV6-RUNX1 Rearrangement in Korean Pediatric Precursor B Cell Acute Lymphoblastic Leukemia[J]. Cancer Res Treat, 2021, 53(2): 567-575. doi: 10.4143/crt.2020.507
[18] Lee JW, Kim SK, Jang PS, et al. Outcome and Prognostic Factors for ETV6/RUNX1 Positive Pediatric Acute Lymphoblastic Leukemia Treated at a Single Institution in Korea[J]. Cancer Res Treat, 2017, 49(2): 446-453. doi: 10.4143/crt.2016.211
[19] Gandemer V, Chevret S, Petit A, et al. Excellent prognosis of late relapses of ETV6/RUNX1-positive childhood acute lymphoblastic leukemia: lessons from the FRALLE 93 protocol[J]. Haematologica, 2012, 97(11): 1743-1750. doi: 10.3324/haematol.2011.059584
[20] 洪艳, 秦亚溱, 徐永艳, 等. 伴ETV6-RUNX1融合基因阳性的儿童急性淋巴细胞白血病患者造血干细胞移植后监测该融合基因的意义[J]. 中华血液学杂志, 2017, 38(8): 680-684.
[21] Hoffmann J, Krumbholz M, Gutiérrez HP, et al. High sensitivity and clonal stability of the genomic fusion as single marker for response monitoring in ETV6-RUNX1-positive acute lymphoblastic leukemia[J]. Pediatr Blood Cancer, 2019, 66(8): e27780.
-
图(1)
表(1)
计量
- 文章访问数: 1299
- PDF下载数: 583
- 施引文献: 0