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

Abstract

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

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.

References 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.

The clinical significance and management strategies of B cell aplasia following CD19 CAR-T cell therapy in pediatric patients

RichHTML

PDF (PC)

Like

Knowledge

Abstract

Cite this article

share this article

References 30

Related Articles 15

Metrics

Comments

Recommended 0

[1]	LUO Mingjing, YU Jiaming, WANG Xiaodong, ZHANG Xiaoling, YU Yue, ZHANG Yu, WEN Feiqiu, LIU Sixi. Clinical analysis of invasive fungal disease secondary to allogeneic hematopoietic stem cell transplantation in 424 children with thalassemia [J]. Journal of Clinical Pediatrics, 2025, 43(1): 21-28.
[2]	LIU Dongxia, JIN Rong, LIN Rongjun. Risk factors analysis of severe refractory Mycoplasma pneumoniae pneumonia complicated with bronchitis obliterans in children [J]. Journal of Clinical Pediatrics, 2025, 43(1): 29-34.
[3]	ZHONG Jinhong, WANG Can, CHEN Fang. Progress in the research of infantile fiberoptic bronchoscopy sedation [J]. Journal of Clinical Pediatrics, 2025, 43(1): 50-55.
[4]	JIANG Weiqin, WANG Jing, CHENG Anna, CHEN Tingting, HUANG Yujuan. Predictors of recurrent febrile seizures during the same febrile illness in children with febrile seizures [J]. Journal of Clinical Pediatrics, 2025, 43(1): 8-13.
[5]	QIU Xiu, WEI Dongmei, LIN Shanshan, XIA Huimin, ZHOU Wenhao. Principles and practice of the Born in Guangzhou Cohort Study [J]. Journal of Clinical Pediatrics, 2024, 42(9): 747-752.
[6]	FAN Jianxia. The origins and development of the healthy life trajectory program: a cohort of community-family-mother-child multidimensional interventions for overweight and obesity in children [J]. Journal of Clinical Pediatrics, 2024, 42(9): 768-773.
[7]	JIANG Tao, LI Shuangjie, TANG Lian, OUYANG Wenxian. Immunobiological properties of peripheral blood MAIT cells in children with chronic hepatitis B [J]. Journal of Clinical Pediatrics, 2024, 42(9): 787-790.
[8]	ZHOU Jie, LIU Keqiang, WANG Jinling, WANG Ying. Megacystis-microcolon-intestinal hypoperistalsis syndrome caused by MYH11 elongating mutation : a case report and literatures review [J]. Journal of Clinical Pediatrics, 2024, 42(9): 798-804.
[9]	CHU Sijia, TANG Jihong. Research progress of central nervous system injury associated with pediatric acute lymphoblastic leukemia and its treatment [J]. Journal of Clinical Pediatrics, 2024, 42(9): 811-816.
[10]	DING Yaping, XIA Shanshan, ZHANG Chenmei. Interpretation of “2023 Children’s Renal Nutrition Working Group Clinical Practice Recommendations: Nutritional Management of Children with Acute Kidney Injury” [J]. Journal of Clinical Pediatrics, 2024, 42(8): 667-672.
[11]	LI Yirong, LI Huiping, GAO Jingyu, XIAO Yuhua, CHEN Xiaomin, LU Yanling, ZHAO Nana, FENG Xiaoqin. Comparison of different doses of cytarabine for induction chemotherapy in children with acute myeloid leukemia in FLAG-IDA regimen [J]. Journal of Clinical Pediatrics, 2024, 42(8): 673-677.
[12]	HUANG Bo, DONG Yanying, SONG Linlan. Clinical characteristics of 348 children with infectious mononucleosis [J]. Journal of Clinical Pediatrics, 2024, 42(8): 678-683.
[13]	WANG Dan, SHAO Jingbo, LI Hong, ZHANG Na, ZHU Jiashi, FU Pan, WANG Zhen. Clinical analysis of 38 cases of hematological malignancies complicated with tumor lysis syndrome in children [J]. Journal of Clinical Pediatrics, 2024, 42(8): 684-690.
[14]	MA Yan, WEI Xingjiao, BAI Hua, ZHANG Yan, TIAN Xinmin, Aqsa Ahmad, LIANG Lijun. Analysis of etiological composition and clinical features of stage 5 chronic kidney disease in children in a tertiary hospital in western China [J]. Journal of Clinical Pediatrics, 2024, 42(8): 697-703.
[15]	WANG Ye, ZHANG Linlin, CHI Zuofei, SUN Ruowen, JIANG Zehui, XU Gang. A case of clinical report of T-lymphoblastic lymphoma secondary to acute promyelocytic leukemia in children [J]. Journal of Clinical Pediatrics, 2024, 42(8): 722-727.