A phase II clinical trial of adoptive transfer of haploidentical natural killer cells for consolidation therapy of pediatric acute myeloid leukemia

Autor: Norman J. Lacayo, Teresa M. Bell, Jeffrey E. Rubnitz, Ching-Hon Pui, William E. Janssen, Huiyun Wu, Barbara Rooney, Kenneth Heym, Raul C. Ribeiro, Stanley Pounds, Rosa Nguyen, Barbara A. Degar, Brandon M. Triplett, Deborah Schiff, Hiroto Inaba, David Cullins, Wing Leung
Rok vydání: 2019
Předmět:
Male
0301 basic medicine
Oncology
Cancer Research
Adoptive cell transfer
medicine.medical_treatment
0302 clinical medicine
Antineoplastic Combined Chemotherapy Protocols
Clinical endpoint
Immunology and Allergy
Cumulative incidence
Child
Myeloid leukemia
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Adoptive Transfer
3. Good health
Fludarabine
Clinical trial
Killer Cells
Natural
Leukemia
Myeloid
Acute
Child
Preschool
030220 oncology & carcinogenesis
Natural killer cells
Molecular Medicine
Female
Vidarabine
medicine.drug
medicine.medical_specialty
Adolescent
Cyclophosphamide
Immunology
Short Report
Human leukocyte antigen
lcsh:RC254-282
Disease-Free Survival
Drug Administration Schedule
03 medical and health sciences
Internal medicine
medicine
Humans
Pharmacology
Chemotherapy
Acute myeloid leukemia
business.industry
Infant
Consolidation Chemotherapy
030104 developmental biology
Transplantation
Haploidentical
Interleukin-2
business
Zdroj: Journal for Immunotherapy of Cancer
Journal for ImmunoTherapy of Cancer, Vol 7, Iss 1, Pp 1-7 (2019)
ISSN: 2051-1426
Popis: Consolidation therapies for children with intermediate- or high-risk acute myeloid leukemia (AML) are urgently needed to achieve higher cure rates while limiting therapy-related toxicities. We determined if adoptive transfer of natural killer (NK) cells from haploidentical killer immunoglobulin–like receptor (KIR)–human leukocyte antigen (HLA)-mismatched donors may prolong event-free survival in children with intermediate-risk AML who were in first complete remission after chemotherapy. Patients received cyclophosphamide (Day − 7), fludarabine (Days − 6 through − 2), and subcutaneous interleukin-2 (Days − 1, 1, 3, 5, 7, and 9). Purified, unmanipulated NK cells were infused on Day 0, and NK cell chimerism and phenotyping from peripheral blood were performed on Days 7, 14, 21, and 28. As primary endpoint, the event-free survival was compared to a cohort of 55 patients who completed chemotherapy and were in first complete remission but did not receive NK cells. Donor NK cell kinetics were determined as secondary endpoints. Twenty-one patients (median age at diagnosis, 6.0 years [range, 0.1–15.3 years]) received a median of 12.5 × 106 NK cells/kg (range, 3.6–62.2 × 106 cells/kg) without major side effects. All but 3 demonstrated transient engraftment with donor NK cells (median peak donor chimerism, 4% [range, 0–43%]). KIR–HLA-mismatched NK cells expanded in 17 patients (81%) and contracted in 4 (19%). However, adoptive transfer of NK cells did not decrease the cumulative incidence of relapse (0.393 [95% confidence interval: 0.182–0.599] vs. 0.35 [0.209–0.495]; P = .556) and did not improve event-free (60.7 ± 10.9% vs. 69.1 ± 6.8%; P = .553) or overall survival (84.2 ± 8.5% vs. 79.1 ± 6.6%; P = .663) over chemotherapy alone. The lack of benefit may result from insufficient numbers and limited persistence of alloreactive donor NK cells but does not preclude its potential usefulness during other phases of therapy, or in combination with other immunotherapeutic agents. www.clinicaltrials.gov , NCT00703820 . Registered 24 June 2008.
Databáze: OpenAIRE
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