High-dose
melphalan (HDM) followed by autologous
stem cell transplantation (ASCT) is a standard treatment for patients with
multiple myeloma. However, lymphocyte reconstitution is impaired after HDM. Recent work has suggested that the
lymphopenia period occurring after various immunosuppressive or
chemotherapy treatments may provide an interesting opportunity for adoptive antitumor
immunotherapy. The objective of this study was to determine an
immunotherapy window after HDM and ASCT, evaluating T cell
lymphopenia, and measuring circulating immune
cytokine concentrations in patients with
multiple myeloma. The counts of T cell subpopulations reached a nadir at day 8 post-ASCT (day 10 post-HDM) and recovered by day 30.
IL-6,
IL-7, and
IL-15 plasma levels increased on a median day 8 post-ASCT, respectively, 35-fold, 8-fold, and 10-fold compared with pre-HDM levels (p < or = 0.05). The increases in
IL-7 and
IL-15 levels were inversely correlated to the absolute lymphocyte count, unlike monocyte or myeloid counts. Furthermore, we have shown that CD3 T cells present in the ASC graft are activated, die rapidly when they are cultured without
cytokine in vitro, and that addition of
IL-7 or
IL-15 could induce their survival and proliferation. In conclusion, the early lymphodepletion period, occurring 4-11 d post-HDM and ASCT, is associated with an increase of circulating immune
cytokines and could be an optimal window to enhance the survival and proliferation of polyclonal T cells present in the ASC autograft and also of specific antimyeloma T cells previously expanded in vitro.