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      Long-term follow-up of idiotype vaccination in human myeloma as a maintenance therapy after high-dose chemotherapy.

      Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K
      Adjuvants, Immunologic, administration & dosage, Antibodies, Anti-Idiotypic, immunology, metabolism, Antibodies, Neoplasm, Antineoplastic Combined Chemotherapy Protocols, Case-Control Studies, Combined Modality Therapy, Follow-Up Studies, Glucocorticoids, Granulocyte-Macrophage Colony-Stimulating Factor, Hematopoietic Stem Cell Transplantation, Hemocyanin, Humans, Hypersensitivity, Delayed, Immunity, Cellular, Immunoglobulin Idiotypes, therapeutic use, Injections, Subcutaneous, Interferon-alpha, Middle Aged, Multiple Myeloma, prevention & control, therapy, Neoplasm Staging, Receptors, Antigen, T-Cell, Remission Induction, Retrospective Studies, Survival Rate, Treatment Outcome, Vaccination

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          Abstract

          The aim of this work was to evaluate the long-term immunological and clinical impact of idiotype (Id) vaccination in multiple myeloma (MM) patients in first remission after high-dose chemotherapy. A total of 15 patients received a series of subcutaneous (s.c.) injections of autologous Id, conjugated to keyhole limpet hemocyanin (KLH) and in association with low doses of GM-CSF. The median duration of follow-up was 110 months from diagnosis. The vaccine induced immune responses that lasted almost 2 years after the end of treatment. Antibody responses included anti-KLH IgM and IgG (90% of patients), anti-KLH IgE (30%), anti-GM-CSF IgG (20%), anti-Id IgG (20%), and anti-Id IgE (30%). Id-specific delayed type hypersensitivity skin tests were positive in 85% of tested patients. Following vaccination, a progressive recovery of T-cell receptor (TCR) diversity was observed and the loss of oligoclonality was significantly correlated with the remission duration. Although Id/KLH conjugates did not eliminate the residual tumor burden, the median progression-free survival, and overall survival were 40 and 82 months, respectively. A retrospective case-matched analysis showed similar results in patients treated with IFN-alpha alone or in association with steroids. This vaccine formulation can overcome Id-specific immune tolerance by inducing clinical responses that are worthy of further investigation.

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