
Clinical significance of minimal residual disease in B-lineage acute lymphoblastic leukemia pediatric patients with different fusion gene backgrounds
WEI Tong, CHEN Xiao-Juan, ZHANG Lu-Yang, ZHANG Ao-Li, ZHU Xiao-Fan
Chinese Journal of Contemporary Pediatrics ›› 2020, Vol. 22 ›› Issue (12) : 1279-1285.
Clinical significance of minimal residual disease in B-lineage acute lymphoblastic leukemia pediatric patients with different fusion gene backgrounds
Objective To study the clinical significance of minimal residual disease (MRD) in B-lineage acute lymphoblastic leukemia (B-ALL) pediatric patients with different fusion gene backgrounds. Methods A retrospective analysis was performed on the medical data of 441 B-ALL children who were treated from January 2008 to April 2015. Among the 441 children, 336 had negative fusion gene, 79 had positive ETV6-RUNX1 fusion gene, and 26 had positive E2A-PBX1 fusion gene. Flow cytometry was used to detect MRD, and the influence of MRD on day 15 (TP1), day 33 (TP2), and week 12 (TP3) of induction therapy on prognosis was analyzed. Results In patients with negative fusion gene, the positive MRD group had significantly lower overall survival (OS) rate and event-free survival (EFS) rate (P < 0.05) and significantly higher recurrence rate and mortality rate at TP1, TP2, and TP3, compared with the negative MRD group (P < 0.05). In patients with positive ETV6-RUNX1, the positive MRD group had significantly lower OS and EFS rates (P < 0.05) and significantly higher recurrence rate and mortality rate (P < 0.05) than the negative MRD group only at TP1. In patients with positive E2A-PBX1, there were no significant differences in the OS rate, recurrence rate, and mortality rate between the positive and negative MRD groups at TP1, TP2, and TP3 (P > 0.05). Conclusions MRD has the most definite prognostic significance in pediatric B-ALL patients with negative fusion gene, while it has unsatisfactory prognostic significance in those with positive ETV6-RUNX1 or positive E2A-PBX1.
B-lineage acute lymphoblastic leukemia / Fusion gene / Minimal residual disease / Prognosis / Child
[1] Dun KA, Vanhaeften R, Batt TJ, et al. BCR-ABL1 gene rearrangement as a subclonal change in ETV6-RUNX1-positive B-cell acute lymphoblastic leukemia[J]. Blood Adv, 2016, 1(2):132-138.
[2] Hong Y, Zhao X, Qin YZ, et al. The prognostic role of E2A-PBX1 expression detected by real-time quantitative reverse transcriptase polymerase chain reaction (RQ-PCR) in B cell acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation[J]. Ann Hematol, 2018, 97(9):1547-1554.
[3] Theunissen P, Mejstrikova E, Sedek L, et al. Standardized flow cytometry for highly sensitive MRD measurements in B-cell acute lymphoblastic leukemia[J]. Blood, 2017, 129(3):347-357.
[4] van Dongen JJ, van der Velden VH, Brüggemann M, et al. Minimal residual disease diagnostics in acute lymphoblastic leukemia:need for sensitive, fast, and standardized technologies[J]. Blood, 2015, 125(26):3996-4009.
[5] 中国医师协会儿科医师分会小儿血液肿瘤专业委员会, 中华医学会儿科学分会血液学组. 儿童急性早幼粒细胞白血病诊疗规范(2018年版)解读[J]. 中华儿科杂志, 2019, 57(10):757-760.
[6] Cui L, Li ZG, Chai YH, et al. Outcome of children with newly diagnosed acute lymphoblastic leukemia treated with CCLG-ALL 2008:the first nation-wide prospective multicenter study in China[J]. Am J Hematol, 2018, 93(7):913-920.
[7] 张之南, 沈悌. 血液病诊断及疗效标准[M]. 第3版. 北京:科学出版社, 2007:19-23.
[8] 中国免疫学会血液免疫分会临床流式细胞术学组. 多参数流式细胞术检测急性白血病及浆细胞肿瘤微小残留病中国专家共识(2017年版)[J]. 中华血液学杂志, 2017, 38(12):1001-1011.
[9] 中国免疫学会血液免疫分会临床流式细胞术学组. 四色流式细胞术用于急性白血病免疫分型的中国专家共识(2015年版)[J]. 中华血液学杂志, 2015, 36(4):265-271.
[10] Wood BL. Principles of minimal residual disease detection for hematopoietic neoplasms by flow cytometry[J]. Cytometry B Clin Cytom, 2016, 90(1):47-53.
[11] 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.
[12] Ampatzidou M, Papadhimitriou SI, Paterakis G, et al. ETV6/RUNX1-positive childhood acute lymphoblastic leukemia (ALL):the spectrum of clonal heterogeneity and its impact on prognosis[J]. Cancer Genet, 2018, 224-225:1-11.
[13] Jeha S, Pei D, Raimondi SC, et al. Increased risk for CNS relapse in pre-B cell leukemia with the t(1;19)/TCF3-PBX1[J]. Leukemia, 2009, 23(8):1406-1409.
[14] 王邢玮, 李本尚, 沈树红, 等. ETV6/RUNX1阳性儿童急性B系淋巴细胞白血病临床预后研究[J]. 临床儿科杂志, 2016, 34(5):321-325.
[15] Metzler M, Mann G, Monschein U, et al. Minimal residual disease analysis in children with t(12;21)-positive acute lymphoblastic leukemia:comparison of Ig/TCR rearrangements and the genomic fusion gene[J]. Haematologica, 2006, 91(5):683-686.
[16] Pui CH, Pei D, Raimondi SC, et al. Clinical impact of minimal residual disease in children with different subtypes of acute lymphoblastic leukemia treated with response-adapted therapy[J]. Leukemia, 2017, 31(2):333-339.
[17] Huang AJ, Huang CM, Tang GS, et al. Impact of clinical utility of MRD assessment with different techniques on survival in acute B lymphoblastic leukemia[J]. Leuk Lymphoma, 2018, 59(5):1073-1083.
[18] Borowitz MJ, Pullen DJ, Shuster JJ, et al. Minimal residual disease detection in childhood precursor-B-cell acute lymphoblastic leukemia:relation to other risk factors. A Children's Oncology Group study[J]. Leukemia, 2003, 17(8):1566-1572.
[19] O'Connor D, Enshaei A, Bartram J, et al. Genotype-specific minimal residual disease interpretation improves stratification in pediatric acute lymphoblastic leukemia[J]. J Clin Oncol, 2018, 36(1):34-43.
[20] Szczepański T. Why and how to quantify minimal residual disease in acute lymphoblastic leukemia?[J]. Leukemia, 2007, 21(4):622-626.