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A phase II clinical trial of infusing haploidentical K562-mb-IL15-41BBL activated and expanded Natural Killer cells as consolidation therapy for pediatric acute myeloblastic leukemia
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  • Lara Maria Gómez-García,
  • Adela Escudero,
  • Carmen Maestre,
  • José Luis Fuster Soler,
  • Antonia Pascual,
  • José Manuel Vagace Valero,
  • María Vela,
  • Beatriz Ruz,
  • Alfonso Navarro Zapata,
  • Lucía Fernández,
  • Adrián Fernández,
  • Alejandra Leivas,
  • Joaquín Martínez-López,
  • Cristina Ferreras,
  • Raquel De Paz,
  • Miguel Blanquer Blanquer,
  • Víctor Galán,
  • Berta González,
  • Dolores Corral,
  • Luisa Sisinni,
  • Isabel Mirones,
  • Antonio Balas,
  • José Luis Vicario,
  • Paula Valle,
  • Alberto M. Borobia,
  • Antonio Pérez-Martínez
Lara Maria Gómez-García
Hospital Clínico Universitario de Valladolid

Corresponding Author:[email protected]

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Adela Escudero
Institute of Medical and Molecular Genetics (INGEMM), Hospital Universitario La Paz
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Carmen Maestre
Translational Research in Pediatric Oncology, Hematopoietic Transplantation & Cell Therapy, IdiPAZ
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José Luis Fuster Soler
Hospital Clinico Universitario Virgen de la Arrixaca
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Antonia Pascual
Hospital Regional Universitario Carlos Haya
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José Manuel Vagace Valero
Paediatric Haematology Department, Maternal and Children Hospital, Complejo Hospitalario Universitario de Badajoz
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María Vela
Translational Research in Pediatric Oncology, Hematopoietic Transplantation & Cell Therapy
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Beatriz Ruz
Institute of Medical and Molecular Genetics (INGEMM), Hospital Universitario La Paz
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Alfonso Navarro Zapata
Translational Research in Pediatric Oncology, Hematopoietic Transplantation & Cell Therapy, IdiPAZ
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Lucía Fernández
Haematological Malignancies Clinical Research Unit, Centro Nacional de Investigaciones Oncológicas (CNIO)
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Adrián Fernández
Haematological Malignancies Clinical Research Unit, Centro Nacional de Investigaciones Oncológicas (CNIO)
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Alejandra Leivas
Haematological Malignancies Clinical Research Unit, Centro Nacional de Investigaciones Oncológicas (CNIO)
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Joaquín Martínez-López
Haematological Malignancies Clinical Research Unit, Centro Nacional de Investigaciones Oncológicas (CNIO)
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Cristina Ferreras
La Paz University Hospital Biomedical Research Foundation,
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Raquel De Paz
Hospital Universitario La Paz
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Miguel Blanquer Blanquer
Hospital Clinico Universitario Virgen de la Arrixaca
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Víctor Galán
La Paz University Hospital
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Berta González
Pediatric Onco-Hematology Department, Hospital Universitario La Paz
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Dolores Corral
Universidad Autónoma de Madrid
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Luisa Sisinni
Hospital Universitario La Paz
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Isabel Mirones
Pediatric Onco-Hematology Department, Hospital Universitario La Paz
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Antonio Balas
Centro de Transfusión Comunidad de Madrid
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José Luis Vicario
Centro de Trasfusiones de la Comunidad de Madrid
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Paula Valle
Clinical Pharmacology Department, Hospital Universitario La Paz
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Alberto M. Borobia
Clinical Pharmacology Department, Hospital Universitario La Paz
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Antonio Pérez-Martínez
HOSPITAL UNIVERSITARIO LA PAZ
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Abstract

Background. Acute myeloid leukemia (AML) accounts for approximately 25% of pediatric leukemia. The long term overall survival rate now approaches 70%, but up 30% relapse. The anti-leukemia properties of Natural Killer (NK) cells and its safety profile has been reported previously at different phases of AML treatment. We proposed a phase II open, a prospective multicenter, non-randomized clinical trial for adoptive infusion of haploidentical K562-mb15-41BBL activated and expanded Natural Killer (NKAE) cells as a consolidation strategy in children with favorable and intermediate-risk AML who were in first complete remission after chemotherapy (NCT02763475). Previous to NKAE cell infusion, patients received a lymphodepleting regimen. After NKAE cell infusion, patients received low doses (1×106/IU/m2) of IL-2 subcutaneously every 48 hours for 2 weeks. Procedure. Seven patients, median age 7.4 years (range, 0.78–15.98), received 13 infusions of NKAE cells, with a median of 36.44×106 NKAE cells/kg (range, 6.92–193.2×106 cells/kg). Results. Three pair donor-recipient were KIR–HLA-mismatched. Donor KIR haplotype score was better in two cases, and neutral in the rest of the cases. Chimerism was observed in 4 patients median chimerism 0.065%, (range 0.05-0.27%). With a median of follow up of 33 moths, 6 (85.7%) patients remain alive and in complete remission. The 3-year overall survival was 83.3% (95% confidence interval 68.1-98.5), and the 3-year relapse cumulative incidence was 28.6% (95% confidence interval 11.5-45.7). Conclusions. This study shows that NKAE cell infusion as a consolidation strategy was feasible and safe but could not improve the pediatric AML relapse rate in this small cohort.