The allure and peril of hematopoietic stem cell transplantation: overcoming immune challenges to improve success

Abstract

Since its inception in the mid-twentieth century, the complication limiting the application and utility of allogeneic hematopoietic stem cell transplantation (allo-HSCT) to treat patients with hematopoietic cancer is the development of graft-versus-host disease (GVHD). Ironically, GVHD is induced by the cells (T lymphocytes) transplanted for the purpose of eliminating the malignancy. Damage ensuing to multiple tissues, e.g., skin, GI, liver, and others including the eye, provides the challenge of regulating systemic and organ-specific GVH responses. Because the immune system is also targeted by GVHD, this both: (a) impairs reconstitution of immunity post-transplant resulting in patient susceptibility to lethal infection and (b) markedly diminishes the individual’s capacity to generate anti-cancer immunity—the raison d’etre for undergoing allo-HSCT. We hypothesize that deleting alloreactive T cells ex vivo using a new strategy involving antigen stimulation and alkylation will prevent systemic GVHD thereby providing a platform for the generation of anti-tumor immunity. Relapse also remains the major complication following autologous HSCT (auto-HSCT). While GVHD does not complicate auto-HSCT, its absence removes significant grant anti-tumor responses (GVL) and raises the challenge of generating rapid and effective anti-tumor immunity early post-transplant prior to immune reconstitution. We hypothesize that effective vaccine usage to stimulate tumor-specific T cells followed by their amplification using targeted IL-2 can be effective in both the autologous and allogeneic HSCT setting. Lastly, our findings support the notion that the ocular compartment can be locally targeted to regulate visual complications of GVHD which may involve both alloreactive and self-reactive (i.e., autoimmune) responses.

Stem cell transplantation for the treatment of patients with type�1 diabetes mellitus: A meta‑analysis

“…Stem cell (SC) transplantation has emerged as a breakthrough treatment due to of the intrinsic regenerative capacity and immunomodulatory properties of SCs ( 17 ), which may achieve arrest of autoimmune β-cell destruction and generate functional β-cells ( 18 ). SC therapy may represent a novel paradigm for optimizing glycemic control in T1DM.…”

Distinct NOD2 polymorphism status is associated with differential outcome in hematopoietic stem cell transplantation: results from a meta-analysis

“…Hematopoietic stem cell transplantation (HSCT) is currently an important strategy for the treatment of many hematological disorders, but the efficacy and safety are frequently limited by concomitant immunologic derangement [1] . Although considerable attention has been focused on how to prevent the detrimental Acute Graft-Versus-Host Disease (aGvHD) while protecting the desired Graft-Versus-Leukemia (GvL) effect, recipients remain susceptible to the other life-threatening post-transplantation complications, including Chronic GvHD (cGvHD), Intestinal GvHD (iGvHD), Transplantation-Related Mortality (TRM), and hematological relapse.…”

Effectiveness of immunoglobulin prophylaxis in reducing clinical complications of hematopoietic stem cell transplantation: a systematic review and meta‐analysis

“…High‐dose chemotherapy and/or radiotherapy maximize the tumoricidal effects, followed by the timely infusion of stem cells to reconstitute the bone marrow and immune system. Pancytopenia and immunodeficiency from therapy may lead to potentially fatal bacterial, fungal, or viral infections such as cytomegalovirus (CMV) and immune complications such as graft‐versus‐disease (GVHD) following transplantation.…”