儿童CD19 CAR-T细胞治疗相关B细胞再生障碍的临床意义和对策

doi:10.12372/jcp.2024.24e0577

摘要/Abstract

摘要：

急性B系淋巴细胞白血病（B-ALL）患儿在CD19 CAR-T细胞治疗后普遍发生B细胞再生障碍（BCA），BCA持续的时间长短对患者的免疫状态及预后会产生影响。对BCA的充分认识有助于临床医师科学、规范、合理地选择治疗策略，减少CAR-T治疗后白血病患儿的感染机会，提高生活质量，改善预后。

关键词: 急性B系淋巴细胞白血病, CD19 CAR-T, B细胞再生障碍, 儿童

Abstract:

B cell aplasia (BCA) is a common adverse side effect in pediatric patients with B-acute lymphoblastic leukemia (B-ALL) following CD19-chimeric antigen receptor T-cell (CD19 CAR-T) therapy. The duration of BCA has an impact on the immune status and prognosis of patients. A thorough understanding of BCA helps physicians choose treatment plans in a scientific, normative, and reasonable manner, reducing the risk of infection in pediatric leukemia patients after CAR-T treatment and improving their prognosis and quality of life.

Key words: B-acute lymphoblastic leukemia, CD19 CAR-T, B cell aplasia, child

卢俊. 儿童CD19 CAR-T细胞治疗相关B细胞再生障碍的临床意义和对策[J]. 临床儿科杂志, 2024, 42(7): 578-582.

LU Jun. The clinical significance and management strategies of B cell aplasia following CD19 CAR-T cell therapy in pediatric patients[J]. Journal of Clinical Pediatrics, 2024, 42(7): 578-582.

参考文献 30

[1]	Inaba H, Mullighan CG. Pediatric acute lymphoblastic leukemia[J]. Haematologica, 2020, 105(11): 2524-2539. doi: 10.3324/haematol.2020.247031 pmid: 33054110
[2]	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.
[3]	Laetsch TW, Maude SL, Rives S, et al. Three-year update of tisagenlecleucel in pediatric and young adult patients with relapsed/refractory acute lymphoblastic leukemia in the ELIANA trial[J]. J Clin Oncol, 2023, 41(9): 1664-1669.
[4]	Curran KJ, Margossian SP, Kernan NA, et al. Toxicity and response after CD19-specific CAR T-cell therapy in pediatric/young adult relapsed/refractory B-ALL[J]. Blood, 2019, 134(26): 2361-2368. doi: 10.1182/blood.2019001641 pmid: 31650176
[5]	Maria Gabelli, Macarena Oporto-Espuelas, Saskia Burridge, et al. Maintenance therapy for early loss of B-cell aplasia after anti-CD19 CAR T-cell therapy[J]. Blood Adv, 2024, 8(8): 1959-1963.
[6]	Levine JE, Grupp SA, Pulsipher MA, et al. Pooled safety analysis of tisagenlecleucel in children and young adults with B cell acute lymphoblastic leukemia[J]. J Immunother Cancer, 2021, 9: e002287.
[7]	Deyà-Martínez A, Alonso-Saladrigues A, García AP, et al. Kinetics of humoral deficiency in CART19-treated children and young adults with acute lymphoblastic leukaemia[J]. Bone Marrow Transplant, 2021, 56(2): 376-386.
[8]	Hill JA, Li D, Hay KA, et al. Infectious complications of CD19-targeted chimeric antigen receptor-modified T-cell immunotherapy[J]. Blood, 2018, 131: 121-130. doi: 10.1182/blood-2017-07-793760 pmid: 29038338
[9]	Locke FL, Ghobadi A, Jacobson CA, et al. Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single-arm, multicentre, phase 1-2 trial[J]. Lancet Oncol, 2019, 20: 31-42. doi: S1470-2045(18)30864-7 pmid: 30518502
[10]	Otani IM, Lehman HK, Jongco AM, et al. Practical guidance for the diagnosis and management of secondary hypogammaglobulinemia: A Work Group Report of the AAAAI Primary Immunodeficiency and Altered Immune Response Committees[J]. J Allergy Clin Immunol, 2022, 149(5): 1525-1560. doi: 10.1016/j.jaci.2022.01.025 pmid: 35176351
[11]	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.
[12]	Hill JA, Li D, Hay KA, et al. Infectious complications of CD19-targeted chimeric antigen receptor-modified T-cell immunotherapy[J]. Blood, 2018, 131: 121-130. doi: 10.1182/blood-2017-07-793760 pmid: 29038338
[13]	Baird JH, Epstein DJ, Tamaresis JS, et al. Immune reconstitution and infectious complications following axicabtagene ciloleucel therapy for large B-cell lymphoma[J]. Blood Adv, 2021, 5(1): 143-155. doi: 10.1182/bloodadvances.2020002732 pmid: 33570626
[14]	Kambhampati S, Sheng Y, Huang CY, et al. Infectious complications in patients with relapsed refractory multiple myeloma after BCMA CAR T-cell therapy[J]. Blood Adv, 2022, 6(7): 2045-2054.
[15]	Schuster SJ, Bishop MR, Tam CS, et al. Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma[J]. N Engl J Med, 2019, 380(1): 45-56.
[16]	Wu X, Cao Z, Chen Z, et al. Infectious complications in pediatric patients undergoing CD19⁺CD22⁺ chimeric antigen receptor T-cell therapy for relapsed/refractory B-lymphoblastic leukemia[J]. Clin Exp Med, 2024, 24(1): 87.
[17]	Deyà-Martínez A, Alonso-Saladrigues A, García AP, et al. Kinetics of humoral deficiency in CART19-treated children and young adults with acute lymphoblastic leukaemia[J]. Bone Marrow Transplant, 2021, 56(2): 376-386.
[18]	Arnold DE, Maude SL, Callahan CA, et al. Subcutaneous immunoglobulin replacement following CD19-specific chimeric antigen receptor T-cell therapy for B-cell acute lymphoblastic leukemia in pediatric patients[J]. Pediatr Blood Cancer, 2020, 67(3): e28092.
[19]	Hill JA, Giralt S, Torgerson TR, et al. CAR-T - and a side order of IgG, to go? - Immunoglobulin replacement in patients receiving CAR-T cell therapy[J]. Blood Rev, 2019, 38: 100596.
[20]	Doan A, Pulsipher MA. Hypogammaglobulinemia due to CAR T-cell therapy[J]. Pediatr Blood Cancer, 2018, 65(4): 10.1002/pbc.26914.
[21]	Los-Arcos I, Iacoboni G, Aguilar-Guisado M, et al. Recommendations for screening, monitoring, prevention, and prophylaxis of infections in adult and pediatric patients receiving CAR T-cell therapy: a position paper[J]. Infection, 2021, 49(2): 215-231.
[22]	Cordeiro A, Bezerra ED, Hirayama AV, et al. Late events after treatment with CD19-targeted chimeric antigen receptor modified T cells[J]. Biol Blood Marrow Transplant, 2020, 26(1): 26-33.
[23]	Bhella S, Majhail NS, Betcher J, et al. Choosing wisely BMT: American society for blood and marrow transplantation and Canadian blood and marrow transplant group's list of 5 tests and treatments to question in blood and marrow transplantation[J]. Biol Blood Marrow Transplant, 2018, 24(5): 909-913.
[24]	Dourthe ME, Rabian F, Yakouben K, et al. Determinants of CD19-positive vs CD19-negative relapse after tisagen-lecleucel for B-cell acute lymphoblastic leukemia[J]. Leukemia, 2021, 35(12): 3383-3393.
[25]	Schultz LM, Eaton A, Baggott C, et al. Outcomes after nonresponse and relapse post-tisagenlecleucel in children, adolescents, and young adults with B-cell acute lymphoblastic leukemia[J]. J Clin Oncol, 2023, 41(2): 354-363.
[26]	Jacoby E. The role of allogeneic HSCT after CAR T cells for acute lymphoblastic leukemia[J]. Bone Marrow Transplant, 2019, 54(Suppl 2): 810-814.
[27]	Wat J, Barmettler S. Hypogammaglobulinemia after chimeric antigen receptor (CAR) T-cell therapy: characteristics, management, and future directions[J]. J Allergy Clin Immunol Pract, 2022, 10(2): 460-466.
[28]	Gabelli M, Oporto Espuelas M, Bonney D, et al. ALL maintenance treatment for early loss of B-cell aplasia after tisagenlecleucel therapy[J]. Blood, 2021, 138(suppl 1): 3859.
[29]	Shiqi L, Jiasi Z, Lvzhe C, et al. Durable remission related to CAR-T persistence in R/R B-ALL and long-term persistence potential of prime CAR-T[J]. Mol Ther Oncolytics, 2023, 29: 107-117.
[30]	Holland EM, Molina JC, Dede K, et al. Efficacy of second CAR-T (CART2) infusion limited by poor CART expansion and antigen modulation[J]. J Immunother Cancer, 2022, 10(5): e004483.