title: Adjuvant Immunotherapy to Improve Outcome in High-Risk Pediatric Sarcomas.
abstract: 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.
  
  
  
  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).
  
  
  
  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.
  
  
  
  Adjuvant immunotherapy may improve survival in patients with metastatic pediatric sarcoma. Clin Cancer Res; 22(13); 3182-91. ©2016 AACR.
authors.affiliation: Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH Clinical Center, Bethesda, Maryland.
authors.forename: Melinda S
authors.initials: MS
authors.lastname: Merchant
authors.affiliation: Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH Clinical Center, Bethesda, Maryland.
authors.forename: Donna
authors.initials: D
authors.lastname: Bernstein
authors.affiliation: Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH Clinical Center, Bethesda, Maryland.
authors.forename: Martha
authors.initials: M
authors.lastname: Amoako
authors.affiliation: Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH Clinical Center, Bethesda, Maryland.
authors.forename: Kristin
authors.initials: K
authors.lastname: Baird
authors.affiliation: Department of Laboratory Medicine, NIH Clinical Center, Bethesda, Maryland.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Fleisher
authors.affiliation: Revimmune, Inc., Bethesda, MD.
authors.forename: Michel
authors.initials: M
authors.lastname: Morre
authors.affiliation: Department of Biostatistics and Data Management, Center for Cancer Research, National Cancer Institute, NIH Clinical Center, Bethesda, Maryland.
authors.forename: Seth M
authors.initials: SM
authors.lastname: Steinberg
authors.affiliation: Department of Transfusion Medicine, NIH Clinical Center, Bethesda, Maryland.
authors.forename: Marianna
authors.initials: M
authors.lastname: Sabatino
authors.affiliation: Department of Transfusion Medicine, NIH Clinical Center, Bethesda, Maryland.
authors.forename: Dave F
authors.initials: DF
authors.lastname: Stroncek
authors.affiliation: Radiology and Imaging Science, NIH Clinical Center, Bethesda, Maryland.
authors.forename: Aradhana M
authors.initials: AM
authors.lastname: Venkatasan
authors.affiliation: Radiology and Imaging Science, NIH Clinical Center, Bethesda, Maryland.
authors.forename: Bradford J
authors.initials: BJ
authors.lastname: Wood
authors.affiliation: Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH Clinical Center, Bethesda, Maryland.
authors.forename: Matthew
authors.initials: M
authors.lastname: Wright
authors.affiliation: Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH Clinical Center, Bethesda, Maryland.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH Clinical Center, Bethesda, Maryland. mackallc@mail.nih.gov.
authors.forename: Crystal L
authors.initials: CL
authors.lastname: Mackall
mesh_terms: D000293:Adolescent; D000328:Adult; D017024:Chemotherapy, Adjuvant / Q000379:methods; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D016219:Immunotherapy, Adoptive / Q000379:methods*; D015851:Interleukin-7 / Q000627:therapeutic use*; D007937:Leukapheresis; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000517:prevention & control; D012208:Rhabdomyosarcoma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D012512:Sarcoma, Ewing / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation*; D055815:Young Adult
chemical_list: C508605:IL7 protein, human; D007155:Immunologic Factors; D015851:Interleukin-7
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