title: Safety of in vitro amplified HLA-haploidentical donor immune cell infusions for childhood malignancies.
abstract: In vitro amplified human leukocyte antigen (HLA)-haploidentical donor immune cell infusion (HDICI) is not commonly used in children. Therefore, our study sought to evaluate its safety for treating childhood malignancies. Between September 2011 and September 2012, 12 patients with childhood malignancies underwent HDICI in Sun Yat-sen University Cancer Center. The median patient age was 5.1 years (range, 1.7-8.4 years). Of the 12 patients, 9 had high-risk neuroblastoma (NB) [7 showed complete response (CR), 1 showed partial response (PR), and 1 had progressive disease (PD) after multi-modal therapies], and 3 had Epstein-Barr virus (EBV)-positive lymphoproliferative disease (EBV-LPD). The 12 patients underwent a total of 92 HDICIs at a mean dose of 1.6×10(8) immune cells/kg body weight: 71 infusions with natural killer (NK) cells, 8 with cytokine-induced killer (CIK) cells, and 13 with cascade primed immune cells (CAPRIs); 83 infusions with immune cells from the mothers, whereas 9 with cells from the fathers. Twenty cases (21.7%) of fever, including 6 cases (6.5%) accompanied with chills and 1 (1.1%) with febrile convulsion, occurred during infusions and were alleviated after symptomatic treatments. Five cases (5.4%) of mild emotion changes were reported. No other adverse events occurred during and after the completion of HDIDIs. Neither acute nor chronic graft versus host disease (GVHD) was observed following HDICIs. After a median of 5.0 months (range, 1.0-11.5 months) of follow-up, the 2 NB patients with PR and PD developed PD during HDICIs. Of the other 7 NB patients in CR, 2 relapsed in the sixth month of HDICIs, and 5 maintained CR with disease-free survival (DFS) ranging from 4.5 to 11.5 months (median, 7.2 months). One EBV-LPD patient achieved PR, whereas 2 had stable disease (SD). Our results show that HDICI is a safe immunotherapy for childhood malignancies, thus warranting further studies.
authors.affiliation: State Key Laboratory of Oncology in South China; Department of Pediatric Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P. R. China. sunxf@sysucc.org.cn, xiajch@sysucc.org.cn.
authors.forename: Fei
authors.initials: F
authors.lastname: Zhang
authors.forename: Xiao-Fei
authors.initials: XF
authors.lastname: Sun
authors.forename: Yong-Qiang
authors.initials: YQ
authors.lastname: Li
authors.forename: Zi-Jun
authors.initials: ZJ
authors.lastname: Zhen
authors.forename: Hai-Xia
authors.initials: HX
authors.lastname: Zheng
authors.forename: Jia
authors.initials: J
authors.lastname: Zhu
authors.forename: Qi-Jing
authors.initials: QJ
authors.lastname: Wang
authors.forename: Su-Ying
authors.initials: SY
authors.lastname: Lu
authors.forename: Jia
authors.initials: J
authors.lastname: He
authors.forename: Juan
authors.initials: J
authors.lastname: Wang
authors.forename: Ke
authors.initials: K
authors.lastname: Pan
authors.forename: Rui-Qing
authors.initials: RQ
authors.lastname: Cai
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.forename: De-Sheng
authors.initials: DS
authors.lastname: Weng
authors.forename: Fei-Fei
authors.initials: FF
authors.lastname: Sun
authors.forename: Jian-Chuan
authors.initials: JC
authors.lastname: Xia
mesh_terms: D002648:Child; D002675:Child, Preschool; D055612:Cytokine-Induced Killer Cells / Q000276:immunology*; D020031:Epstein-Barr Virus Infections / Q000628:therapy; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D016219:Immunotherapy, Adoptive; D007223:Infant; D007694:Killer Cells, Natural / Q000276:immunology*; D008232:Lymphoproliferative Disorders / Q000628:therapy* / Q000821:virology; D008297:Male; D009447:Neuroblastoma / Q000628:therapy*; D014184:Transplantation, Homologous; D016896:Treatment Outcome