Interleukin-15 Affects Patient Survival through Natural Killer Cell Recovery after Autologous Hematopoietic Stem Cell Transplantation for Non-Hodgkin Lymphomas

Natural killer cells at day 15 (NK-15), after autologous peripheral blood hematopoietic stem cell transplantation (APHSCT), is a prognostic factor for overall survival (OS) and progression-free survival (PFS) in non-Hodgkin lymphoma (NHL). The potential role of the immunologic (homeostatic) environment affecting NK-15 recovery and survival post-APHSCT has not been fully studied. Therefore, we evaluate prospectively the cytokine profile in 50 NHL patients treated with APHSCT. Patients with an interleukin-15 (IL-15) ≥ 76.5 pg/mL at day 15 post-APHSCT experienced superior OS and PFS compared with those who did not; median OS; not reached versus 19.2 months, P < .002; and median PFS; not reached versus 6.8 months, P < .002, respectively. IL-15 was found to correlate with (rs = 0.7, P < .0001) NK-15. Multivariate analysis showed only NK-15 as a prognostic factor for survival, suggesting that the survival benefit observed by IL-15 is most likely mediated by enhanced NK cell recovery post-APHSCT

Autologous Graft-versus-Tumor Effect: Reality or Fiction?

In contrast to allogeneic hematopoietic stem cell transplantation, the current dogma is not an evidence of graft-versus-tumor effect in autologous hematopoietic stem cell transplantation; thus, it is assumed that autologous hematopoietic stem cell transplantation only relies on the high-dose chemotherapy to improve clinical outcomes. However, recent studies argue in favor of the existence of an autologous graft-versus-tumor without the detrimental complications of graft-versus-host disease due to the nonspecific immune response from the infused donor alloreactive immune effector cells in allogeneic hematopoietic stem cell transplantation. Herein, this paper reviews the clinical evidence of an autologous graft-versus-tumor effect based on the autograft collected and infused host immune effector cells and host immunity recovery after autologous hematopoietic stem cell transplantation affecting clinical outcomes in cancer patients

The Impact of Infused Autograft Absolute Numbers of Immune Effector Cells on Survival Post-Autologous Stem Cell Transplantation

Autologous stem cell transplantation treatment has been viewed as a therapeutic modality to enable the infusion of higher doses of chemotherapy to eradicate tumor cells. Nevertheless, recent reports have shown that, in addition to stem cells, infusion of autograft immune effector cells produces an autologous graft-versus-tumor effect, similar to the graft-versus-tumor effect observed in allogeneic-stem cell transplantation, but without the clinical complications of graft-versus-host disease. In this review, I assess the impact on clinical outcomes following infusions of autograft-antigen presenting cells, autograft innate and adaptive immune effector cells, and autograft immunosuppressive cells during autologous stem cell transplantation. This article is intended to provide a platform to change the current paradigmatic view of autologous stem cell transplantation, from a high-dose chemotherapy-based treatment to an adoptive immunotherapeutic intervention

Natural Killer Cells Are Key Host Immune Effector Cells Affecting Survival in Autologous Peripheral Blood Hematopoietic Stem Cell Transplantation

The infusion of autograft immune effector cells directly impacts the clinical outcomes of patients treated with autologous peripheral blood hematopoietic stem cell transplantation, suggesting the possibility of an autologous graft-versus tumor cells. Furthermore, the early recovery of immune effector cells also affects survival post-autologous peripheral blood hematopoietic stem cell transplantation. Natural killer cells are among the immune effector cells reported to be collected, infused, and recovered early post-autologous peripheral blood hematopoietic stem cell transplantation. In this review, I attempt to give an update on the role of natural killer cells regarding improving survival outcomes on patients treated with autologous peripheral blood hematopoietic stem cell transplantation

Autologous Graft-versus-Tumor Effect: Reality or Fiction?

In contrast to allogeneic hematopoietic stem cell transplantation, the current dogma is not an evidence of graft-versus-tumor effect in autologous hematopoietic stem cell transplantation; thus, it is assumed that autologous hematopoietic stem cell transplantation only relies on the high-dose chemotherapy to improve clinical outcomes. However, recent studies argue in favor of the existence of an autologous graft-versus-tumor without the detrimental complications of graft-versus-host disease due to the nonspecific immune response from the infused donor alloreactive immune effector cells in allogeneic hematopoietic stem cell transplantation. Herein, this paper reviews the clinical evidence of an autologous graft-versus-tumor effect based on the autograft collected and infused host immune effector cells and host immunity recovery after autologous hematopoietic stem cell transplantation affecting clinical outcomes in cancer patients

Autograft mediated adoptive immunotherapy of cancer in the context of autologous stem cell transplantation

The infused stem cell autograft in autologous stem cell transplantation (ASCT) has been viewed mainly as hematologic rescue from the myelosuppressive side effect of conditioning regimens. However, recent reports have shown that the immune effector cells collected at the same time as the stem cells can produce an autologous graft-versus-tumor effect, similar to the graft-versus-tumor effect seen in allogeneic stem cell transplantation without the detrimental effects of graft-versus-host disease. In this article, we review the different immune effector cells collected and infused from the stem cell autograft and their association with clinical outcome post-ASCT, suggesting that ASCT can be viewed not only as a therapeutic maneuver to recover bone marrow function after deliver high-dose chemotherapy, but also as an adoptive immunotherapeutic intervention capable of eradicating residual tumor cells in patients with cancer