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
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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