Cytokine-Induced Killer Cell Therapy as a Postremission Strategy in High-Risk Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation: A Prospective Investigator-Initiated Clinical Study

In high-risk non-Hodgkin lymphoma (NHL) with complete remission (CR), intensive chemotherapy and autologous stem cell transplantation (ASCT) provide additional benefits. However, despite the benefits, minimal residual disease-induced relapse and high-risk delayed immune-reconstitution-based-atypical infections contribute to early post-transplant morbidity and mortality. This highlights the need for innovative strategies to refine treatment application and improve outcomes. Thus, we aimed to find an innovative strategy to refine therapeutic applications and improve their outcomes by examining the potential of cytokine-induced killer (CIK) cells. We hypothesized that our method would improve post-transplant outcomes in high-grade aggressive NHL by targeting residual disease and supporting immune recovery, thereby enhancing progression-free survival (PFS) and reducing opportunistic infection risk. In this single-center study, we prospectively evaluated early post-ASCT CIK cell-infusion administration in 20 high-risk patients with NHL who achieved complete remission, after upfront or salvage treatment. The primary and secondary endpoints were 2-year PFS and immune reconstitution-associated safety profile evaluation, respectively. CIK cells from participants with a high proportion of CD3+ cells (median, 97.5%), including CD3+CD56+ natural killer-like T cells (median, 28.6%), demonstrated potent cytotoxic effects through NKG2D-receptor overexpression (median, 73.6%) and in vitro lysis of K562 cell line. Post-ASCT, CIK cells (2.65 × 10⁷ to 3.78 × 10⁹/kg) were infused at a median 14 (10 to 18)-day duration; only two patients were mildly febrile; 79.8% (95% confidence interval, 49.4% to 93.1%) achieved median 2-yr PFS (22.6 [2.3 to 37.9] mo), without uncontrolled cytomegalovirus (CMV) DNAemia or infections with intact CMV-pp65-specific interferon-γ response in CIK-cell product. CIK cells were associated with improved functional activity of T-cell subsets during early post-transplant immune reconstitution. Post-ASCT CIK cell infusion as post-remission therapy for high-risk NHL may prevent relapse and opportunistic infections.