A phase I/II trial of interleukin-15--stimulated natural killer cell infusion after haplo-identical stem cell transplantation for pediatric refractory solid tumors.
OBJECTIVE
Preliminary data suggest that T-cell-depleted haplo-identical stem cell transplantation (haplo-SCT) has a clinically beneficial allograft-versus-tumor effect associated with natural killer (NK) cell immune reconstitution.


METHODS
This phase I/II trial descriptively evaluates the feasibility of interleukin (IL)-15-stimulated NK cell infusion after haplo-SCT in pediatric patients with refractory solid tumors.


RESULTS
Six patients received an IL-15-stimulated NK cell infusion at 30 days after haplo-SCT. The mean number of infused NK cells per product was 11.3 × 10(6)/kg (range, 3-27 × 10(6)/kg). The T-cell count was <1 × 10(3)/kg in all patients (range, 0-0.75 × 10(3)/kg). No toxic effects related to IL-15--stimulated NK cell infusion were observed. Four of the six patients showed a clinical response (one achieved very good partial remission, two achieved partial remission and one had stable disease). One patient had progressive disease, and the response was not evaluated in the remaining patient. After a median follow-up period of 310 days, all patients had died: four of cancer relapse, one of cancer-associated thrombotic micro-angiopathy and one of acute graft-versus-host disease.


CONCLUSIONS
The adoptive transfer of allogeneic IL-15--stimulated NK cells might be feasible and safe in heavily pretreated pediatric patients with refractory solid tumors, though the advanced stage of disease and toxic effects of haplo-SCT may limit the efficacy of NK cell infusion in this population.
Department of Pediatric Hemato-Oncology and Stem Cell Transplantation, Hospital Infantil Universitario La Paz, Madrid, Spain. Electronic address: aperezmartinez@salud.madrid.org.
Antonio
A
Pérez-Martínez
Clinical Research Program, Cancer Research National Centre, Madrid, Spain.
Lucía
L
Fernández
Innate Immune Research Group, IdiPAZ, Madrid, Spain.
Jaime
J
Valentín
Pediatric Department, Universidad Autónoma, Madrid, Spain.
Isabel
I
Martínez-Romera
Pediatric Department, Universidad Autónoma, Madrid, Spain.
María Dolores
MD
Corral
GMP Facility, Department of Hemato-Oncology and Stem Cell Transplantation, Hospital Infantil Universitario Niño Jesús, Madrid, Spain; Department of Hemato-Oncology and Stem Cell Transplantation, Hospital Infantil Universitario Niño Jesús, Madrid, Spain.
Manuel
M
Ramírez
Department of Hemato-Oncology and Stem Cell Transplantation, Hospital Infantil Universitario Niño Jesús, Madrid, Spain.
Lorea
L
Abad
GMP Facility, Department of Hemato-Oncology and Stem Cell Transplantation, Hospital Infantil Universitario Niño Jesús, Madrid, Spain.
Sandra
S
Santamaría
Department of Hemato-Oncology and Stem Cell Transplantation, Hospital Infantil Universitario Niño Jesús, Madrid, Spain.
Marta
M
González-Vicent
Department of Radiology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain.
Sara
S
Sirvent
Department of Hemato-Oncology and Stem Cell Transplantation, Hospital Infantil Universitario Niño Jesús, Madrid, Spain.
Julián
J
Sevilla
Centro de Transfusiones de la Comunidad de Madrid, Madrid, Spain.
José Luis
JL
Vicario
Department of Pathology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain.
Inmaculada
I
de Prada
Department of Hemato-Oncology and Stem Cell Transplantation, Hospital Infantil Universitario Niño Jesús, Madrid, Spain.
Miguel Ángel
MÁ
Diaz
D000293:Adolescent; D002648:Child; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000276:immunology; D006801:Humans; D019409:Interleukin-15 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology / Q000637:transplantation*; D018655:Lymphocyte Count; D008297:Male; D009369:Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D033581:Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D013601:T-Lymphocytes / Q000276:immunology; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D019409:Interleukin-15
IL-15–stimulated NK cells; haplo-identical stem cell transplantation; pediatric solid tumors