Adjuvant Immunotherapy to Improve Outcome in High-Risk Pediatric Sarcomas
Autor: | Bradford J. Wood, Donna Bernstein, Martha Amoako, Hua Zhang, Thomas A. Fleisher, Marianna Sabatino, Matthew Wright, Crystal L. Mackall, Seth M. Steinberg, Michel Morre, Dave Stroncek, Kristin Baird, Melinda S. Merchant, Aradhana M. Venkatasan |
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Rok vydání: | 2015 |
Předmět: |
0301 basic medicine
Oncology Adult Male Cancer Research medicine.medical_specialty Adolescent medicine.medical_treatment T-Lymphocytes Population Sarcoma Ewing Immunotherapy Adoptive Disease-Free Survival Article 03 medical and health sciences Young Adult 0302 clinical medicine Internal medicine Rhabdomyosarcoma medicine Humans Immunologic Factors Leukapheresis education Child education.field_of_study Chemotherapy business.industry Interleukin-7 Immunotherapy Dendritic Cells medicine.disease Combined Modality Therapy Regimen 030104 developmental biology Chemotherapy Adjuvant 030220 oncology & carcinogenesis Child Preschool Immunology Female Sarcoma Neoplasm Recurrence Local business Adjuvant |
Zdroj: | Clin Cancer Res |
ISSN: | 1557-3265 |
Popis: | Purpose: Patients with metastatic or relapsed pediatric sarcomas receive cytotoxic regimens that induce high remission rates associated with profound lymphocyte depletion, but ultimately few survive long term. We administered adjuvant immunotherapy to patients with metastatic and recurrent pediatric sarcomas in an effort to improve outcomes. Experimental Design: Mononuclear cells were collected via apheresis, and tumor lysate was acquired via percutaneous biopsy at enrollment. Participants received standard antineoplastic therapy, followed by autologous lymphocytes, tumor lysate/keyhole limpet hemocyanin–pulsed dendritic cell vaccinations ± recombinant human IL7. Primary outcomes were toxicity and vaccine responses. Secondary outcomes were immune reconstitution, event-free survival, and overall survival (OS). Results: Forty-three patients enrolled and 29 received immunotherapy. The regimen was well tolerated. Intent-to-treat analysis demonstrated 5-year OS of 51% with significant differences based upon histologic group (63% vs. 0% for Ewing/rhabdomyosarcoma vs. other sarcomas) and response to standard therapy (74% no residual disease vs. 0% residual disease). Five-year intent-to-treat OS of patients with newly diagnosed metastatic Ewing/rhabdomyosarcoma was 77%, higher than previously reported in this population and higher than observed in a similar group treated with an earlier adjuvant immunotherapy regimen (25% 5-year OS). T-cell responses to autologous tumor lysate were identified in 62% of immunotherapy recipients, and survival was higher in those patients (73% 5-year OS with vs. 37% without immune response, P = 0.017). Immune reconstitution, measured by CD4 count recovery, was significantly enhanced in subjects treated with recombinant human IL7. Conclusions: Adjuvant immunotherapy may improve survival in patients with metastatic pediatric sarcoma. Clin Cancer Res; 22(13); 3182–91. ©2016 AACR. |
Databáze: | OpenAIRE |
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