Safety and immune cell kinetics after donor natural killer cell infusion following haploidentical stem cell transplantation in children with recurrent neuroblastoma

Autoři: Young Bae Choi aff001;  Meong Hi Son aff002;  Hee Won Cho aff002;  Youngeun Ma aff003;  Ji Won Lee aff002;  Eun-Suk Kang aff004;  Keon Hee Yoo aff002;  Jung Hyun Her aff005;  Okjae Lim aff006;  Miyoung Jung aff005;  Yu Kyeong Hwang aff005;  Ki Woong Sung aff002;  Hong Hoe Koo aff002
Působiště autorů: Department of Pediatrics, Chungbuk National University Hospital, Cheongju, Republic of Korea aff001;  Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea aff002;  Department of Pediatrics, Seoul National University Bundang Hospital, Sungnam, Republic of Korea aff003;  Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea aff004;  Cell Therapy Research Center, GC LabCell, Yongin, Republic of Korea aff005;  MOGAM Institute for Biomedical Research, Yongin, Republic of Korea aff006
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
doi: 10.1371/journal.pone.0225998



Under the hypothesis that early natural killer cell infusion (NKI) following haploidentical stem cell transplantation (haplo-SCT) will reduce relapse in the early post-transplant period, we conducted a pilot study to evaluate the safety and feasibility of NKI following haplo-SCT in children with recurrent neuroblastoma who failed previous tandem high-dose chemotherapy and autologous SCT.


We used the high-dose 131I-metaiodobenzylguanidine and cyclophosphamide/fludarabine/anti-thymocyte globulin regimen for conditioning and infused 3 × 107/kg of ex-vivo expanded NK cells derived from a haploidentical parent donor on days 2, 9, and 16 post-transplant. Interleukin-2 was administered (1 × 106 IU/m2/day) subcutaneously to activate infused donor NK cells on days 2, 4, 6, 9, 11, 13, 16, 18, and 20 post-transplant.


Seven children received a total of 19 NKIs, and NKI-related acute toxicities were fever (n = 4) followed by chills (n = 3) and hypertension (n = 3); all toxicities were tolerable. Grade ≥II acute GVHD and chronic GVHD developed in two and five patients, respectively. Higher amount of NK cell population was detected in peripheral blood until 60 days post-transplant than that in the reference cohort. Cytomegalovirus and BK virus reactivation occurred in all patients and Epstein-Barr virus in six patients. Six patients died of relapse/progression (n = 5) or treatment-related mortality (n = 1), and one patient remained alive.


NKI following haplo-SCT was relatively safe and feasible in patients with recurrent neuroblastoma. Further studies to enhance the graft-versus-tumor effect without increasing GVHD are needed.

Klíčová slova:

Adverse reactions – Cancer treatment – Fevers – Haplotypes – Neuroblastoma – NK cells – Stem cell transplantation – Toxicity


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