title: Anti-CD19 chimeric antigen receptor-modified T cells for B-cell malignancies: a systematic review of efficacy and safety in clinical trials.
abstract: OBJECTIVE
  Administration of anti-CD19 chimeric antigen receptor (CAR)-modified T cells for B-cell malignancies has been remarkably effective in recent clinical trials. To investigate the critical parameters affecting efficacy and evaluated the safety of using CAR T cells targeting CD19 in B-lineage malignancies. We performed a systematic review of reported phase I clinical trials using CAR T cells targeting CD19 in B-lineage malignancies.
  
  
  METHODS
  We searched Medline and Embase for studies on anti-CD19 CAR-modified T cells in patients with B-cell malignancies in October 2014. Univariate analyses were performed using the Kaplan-Meier method, and a Cox regression model was used to determine the independent prognostic factors of progression-free survival (PFS).
  
  
  RESULTS
  Six trials involving 50 patients were included in this review. After CAR T-cell infusion, the overall response rate was 48% (complete responses in 24%). The 6-month PFS and 1-year PFS were 43% and 27%, respectively. Statistically significant factors favorably influencing PFS were conditioning chemotherapy (P < 0.001), B-cell aplasia (P = 0.040), and durable persistence of CAR T cells (P = 0.013) in univariate analyses. After multivariate analysis, conditioning chemotherapy remained as an independent prognostic factor for PFS. The most common adverse events were fever, hypotension, rigor, fatigue, bacteremia, chill, dyspnea, and headache, but all were temporary and resolved.
  
  
  CONCLUSIONS
  Anti-CD19 CAR-modified T cells have shown therapeutic efficacy in patients with B-lineage malignancies and were well tolerated in most patients. Conditioning chemotherapy is a prerequisite to improve the clinical outcome.
authors.affiliation: Department of Hematology, Guangdong NO. 2 Provincial People's Hospital, Guangdong, Guangzhou, China.
authors.forename: Yangmin
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Hematology, Guangdong NO. 2 Provincial People's Hospital, Guangdong, Guangzhou, China.
authors.forename: Youping
authors.initials: Y
authors.lastname: Tan
authors.affiliation: Department of Hematology, Guangdong NO. 2 Provincial People's Hospital, Guangdong, Guangzhou, China.
authors.forename: Ruiming
authors.initials: R
authors.lastname: Ou
authors.affiliation: Department of Hematology, Guangdong NO. 2 Provincial People's Hospital, Guangdong, Guangzhou, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhong
authors.affiliation: Department of Hematology, Guangdong NO. 2 Provincial People's Hospital, Guangdong, Guangzhou, China.
authors.forename: Liling
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Department of Hematology, Guangdong NO. 2 Provincial People's Hospital, Guangdong, Guangzhou, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Du
authors.affiliation: Department of Hematology, Guangdong NO. 2 Provincial People's Hospital, Guangdong, Guangzhou, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Hematology, Guangdong NO. 2 Provincial People's Hospital, Guangdong, Guangzhou, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Huang
mesh_terms: D000328:Adult; D018941:Antigens, CD19 / Q000235:genetics / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology*; D001521:Behavior Therapy / Q000379:methods; D060846:Cell Engineering; D002986:Clinical Trials as Topic; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive; D016393:Lymphoma, B-Cell / Q000175:diagnosis* / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000637:transplantation*; D016896:Treatment Outcome
chemical_list: D018941:Antigens, CD19; C000604811:CD19 molecule, human; D011948:Receptors, Antigen, T-Cell
keywords: B-cell malignancy; CD19; chimeric antigen receptor; survival analysis