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

Autor: Young Bae Choi, Meong Hi Son, Hee Won Cho, Youngeun Ma, Ji Won Lee, Eun-Suk Kang, Keon Hee Yoo, Jung Hyun Her, Okjae Lim, Miyoung Jung, Yu Kyeong Hwang, Ki Woong Sung, Hong Hoe Koo
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: PLoS ONE, Vol 14, Iss 12, p e0225998 (2019)
Druh dokumentu: article
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0225998
Popis: INTRODUCTION: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. METHODS: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. RESULTS: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. CONCLUSION: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.
Databáze: Directory of Open Access Journals
Nepřihlášeným uživatelům se plný text nezobrazuje