Safety and immune cell kinetics after donor natural killer cell infusion following haploidentical stem cell transplantation in children with recurrent neuroblastoma
Autor: | Keon Hee Yoo, Ji Won Lee, Jung Hyun Her, Youngeun Ma, Hee Won Cho, Young Bae Choi, Hong Hoe Koo, Miyoung Jung, Okjae Lim, Ki Woong Sung, Meong Hi Son, Eun-Suk Kang, Yu Kyeong Hwang |
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Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
Male
Heredity Cell Transplantation medicine.medical_treatment Cancer Treatment Graft vs Host Disease Fevers Cell Count NK cells Toxicology Pathology and Laboratory Medicine Gastroenterology Immunotherapy Adoptive Neuroblastoma 0302 clinical medicine Immune Reconstitution Cellular types Blood and Lymphatic System Procedures Blastomas Child education.field_of_study Multidisciplinary Immune cells Hematopoietic Stem Cell Transplantation Fludarabine Killer Cells Natural Genetic Mapping medicine.anatomical_structure Treatment Outcome surgical procedures operative Oncology 030220 oncology & carcinogenesis Child Preschool White blood cells Medicine Chills Female medicine.symptom medicine.drug Research Article medicine.medical_specialty Cell biology Blood cells Cyclophosphamide Science Population Immunology Surgical and Invasive Medical Procedures Natural killer cell Immunophenotyping 03 medical and health sciences Signs and Symptoms Adverse Reactions Diagnostic Medicine Internal medicine medicine Genetics Humans education Neoplasm Staging Medicine and health sciences Pharmacology Chemotherapy Transplantation Chimera Transplantation Biology and life sciences Toxicity business.industry Infant Cancers and Neoplasms Immunotherapy Animal cells Haplotypes Transplantation Haploidentical business Biomarkers 030215 immunology Stem Cell Transplantation |
Zdroj: | PLoS ONE, Vol 14, Iss 12, p e0225998 (2019) PLoS ONE |
ISSN: | 1932-6203 |
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: | OpenAIRE |
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