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A pilot study of consolidative immunotherapy in patients with high-risk pediatric sarcomas

  1. Author:
    Mackall, C. L.
    Rhee, E. H.
    Read, E. J.
    Khuu, H. M.
    Leitman, S. F.
    Bernstein, D.
    Tesso, M.
    Long, L. M.
    Grindler, D.
    Merino, M.
    Kopp, W.
    Tsokos, M.
    Berzofsky, J. A.
    Helman, L. J.

  2. Author Address

    Mackall, Crystal L.; Rhee, Eunice H.; Bernstein, Donna, Long, Lauren M.; Grindler, David, Merino, Margret, Helman, Lee J.] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Tsokos, Maria] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Berzofsky, Jay A.] NCI, Vaccine Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Read, Elizabeth J.; Khuu, Hanh M.] NIH, Cell Proc Sect, Bethesda, MD 20892 USA. [Leitman, Susan F.] NIH, Apheresis Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. [Tesso, Merertu] HarrisTech Serv Corp, Colorado Springs, CO USA. [Kopp, William] SAIC Frederick Inc, NCI, Clin Support Lab, Frederick, MD USA.
    1. Year: 2008
  2. Journal: Clinical Cancer Research
    1. 14
    2. 15
    3. Pages: 4850-4858
  4. Type of Article: Article
  1. Abstract:

    Purpose: Patients with metastatic or recurrent Ewing's sarcoma family of tumors and alveolar rhabdomyosarcoma have < 25% 5-year survival in most studies. This study administered a novel immunotherapy regimen aimed at consolidating remission in these patients. Experimental Design: Fifty-two patients with translocation positive, recurrent, or metastatic Ewing's sarcoma family of tumors or alveolar rhabdomyosarcoma underwent prechemotherapy cell harvest via apheresis for potential receipt of immunotherapy. Following completion of standard multimodal therapy, 30 patients ultimately initiated immunotherapy and were sequentially assigned to three cohorts. All cohorts received autologous T cells, influenza vaccinations, and dendritic cells pulsed with peptides derived from tumor-specific translocation breakpoints and E7, a peptide known to bind HLA-A2. Cohort 1 received moderate-dose recombinant human interleukin-2 (rhIL-2), cohort 2 received low-dose rhIL-2, and cohort 3 did not receive rhIL-2. Results: All immunotherapy recipients generated influenza-specific immune responses, whereas immune responses to the translocation breakpoint peptides occurred in 39%, and only 25% of HLA-A2(+) patients developed E7-specific responses. Toxicity was minimal. Intention-to-treat analysis revealed a 31% 5-year overall survival for all patients apheresed (median potential follow-up 7.3 years) with a 43% 5-year overall survival for patients initiating immunotherapy. Conclusions: Consoliclative immunotherapy is a scientifically based and clinically practical approach for integrating immunotherapy into a multimodal regimen for chemoresponsive cancer. Patients receiving immunotherapy experienced minimal toxicity and favorable survival. The robust influenza immune responses observed suggest that postchemotherapy immune incompetence will not fundamentally limit this approach. Future studies will seek to increase efficacy by using more immunogenic antigens and more potent dendritic cells.

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External Sources

  1. PMID: 18676758

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