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Tumor immunology
Published in Gabriel Virella, Medical Immunology, 2019
Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative option for many patients with hematological malignancies such as acute leukemias, lymphoma, and some cases of multiple myeloma. The goal of transplant is to generate a donor-derived allogeneic immune response against a patient's hematological cancer; this response is known as the graft-versus-tumor effect. Unlike other immune therapies, allogeneic HSCT does not target a specific immune evasion mechanism or a specific tumor target, but it aims to break tolerance against cancer at a much broader level. Allogeneic HSCT is an intensive process, and the treatment-related mortality can be as high as 30%. The success rate of allogeneic transplant varies depending on the disease, but in all cases, the possibility of success outweighs the chances of transplant-related mortality. One of the most serious complications from allogeneic HSCT is graft-versus-host disease (GVHD). GVHD occurs when the donor's immune system recognizes the patient's tissues as foreign and mounts an immune response against those tissues. Our ability to prevent and control GVHD has dramatically improved over the last two decades, but it remains a significant cause of morbidity and mortality in transplant patients.
Immunomodulators: What is the evidence for use in mycoses?
Published in Mahmoud A. Ghannoum, John R. Perfect, Antifungal Therapy, 2019
IL-2 plays a major role in promoting the graft-versus-tumor effect after stem cell transplantation. Since this is often a desirable outcome after myeloablative therapy, investigators in Israel conducted a trial to determine whether routine administration of this cytokine would improve clinical outcomes in patients undergoing stem cell transplantation. The investigators noted that 2 of the first 12 patients treated with IL-2 therapy developed invasive fungal infections; this was a much higher incidence of systemic mycoses than would be expected from historic data. Therefore, the trial was terminated prematurely [61]. However, subsequent published studies of low-dose IL-2 administration in stem cell transplantation reported an overall beneficial effect, and no significant increases in observed infections [62]. The potential for unexpected, dose-related effects of cytokine therapy on invasive fungal infections underscores that novel therapy should be conducted in the setting of monitored clinical trials that are designed to identify adverse events.
Future therapies in lung transplantation
Published in Wickii T. Vigneswaran, Edward R. Garrity, John A. Odell, LUNG Transplantation, 2016
Elizabeth A. Lendermon, John F. McDyer
Several clinical case reports have demonstrated durable renal allograft acceptance in the absence of immunosuppressive therapy in patients who were previously treated with myeloablative bone marrow transplantation (BMT) from the same donor.69–72 However, that myeloablation and full donor chimerism may not be necessary for induction of durable solid-organ allograft tolerance with BMT is becoming clear. An association between the development of mixed lymphohematopoietic chimerism after nonmyeloablative BMT and tolerance of a solid-organ allograft from the same donor has clearly been demonstrated in multiple models of transplantation in rodents and large animals.73–78 In 1999, Spitzer and colleagues reported the first intentional induction of mixed lymphohematopoietic chimerism after a nonmyeloablative preparative regimen to treat multiple myeloma and establish renal allograft tolerance.79 In their research, a preparative regimen consisting of cyclophosphamide, antithymocyte globulin, thymic irradiation, and initiation of cyclosporine was used before BMT, which was immediately followed by renal transplantation. Cyclosporine was continued initially but gradually tapered off by day 73 after transplantation. By day 147, despite two donor lymphocyte infusions for a graft-versus-tumor effect, the level of donor CD3+ and CD3- cells found was less than 1%, but renal function nonetheless remained normal until at least day 174 after transplantation, thus suggesting donor alloantigen tolerance. This finding is consistent with data in nonhuman primates suggesting that even transient donor chimerism is sufficient for donor-specific tolerance of renal grafts.77 A clinical trial examining the use of combined BMT and renal transplantation in patients with multiple myeloma and end-stage renal disease (NCT00854139) is currently under way, and whether durable allograft acceptance in the absence of immunosuppression is established will be of particular importance to the field of transplant immunology.
Graft versus host disease: a pediatric perspective
Published in Expert Review of Ophthalmology, 2019
Simon SM Fung, Uri Elbaz, Kamiar Mireskandari, Asim Ali
Chronic oGVHD represents the majority of disease burden in the long term, and is the focus in much of the existing literature on disease management. The severity of ocular disease does not correlate well with that of systemic disease. Therefore, treatment of ocular GVHD should be organ-specific since increasing the intensity of systemic immunosuppression is not considered an optimal approach for ocular GVHD [11]. However, in patients with both active ocular and multi-organ GVHD, systemic immunosuppression could be considered. It should be borne in mind that changes in systemic immunosuppression would also affect graft-versus-tumor effect that is essential for disease remission in cases with hematopoietic malignancy.
A systematic literature review of incidence, mortality, and relapse of patients diagnosed with chronic graft versus host disease
Published in Expert Review of Hematology, 2019
Marcell Csanadi, Tamas Agh, Attila Tordai, Thomas Webb, Dusha Jeyakumaran, Nishan Sengupta, Frida Schain, Jonas Mattsson
According to the literature, patients with chronic GVHD have improved survival compared to transplanted patients without chronic GVHD. This favorable survival outcome might be explained by a significantly lower risk of relapse [20,35,62–66] caused by the presence of a potent graft versus tumor effect [42,54]. Nevertheless, the potential benefits of the increased graft versus tumor effect might be outweighed by the increased risk of developing more severe chronic GVHD associated with higher NRM [55] and impaired quality of life [4,5].
Celebrating Life Through City of Hope’s Bone Marrow Transplant Program
Published in Oncology Issues, 2020
City of Hope was also one of the first institutions to do BMTs in patients over the age of 50 and now many patients over the age of 70 are undergoing successful transplants to cure their disease. We did this by approaching the procedure based on the idea of a reduced intensity, or “mini” transplant. This breakthrough method relies less on heavy doses of chemotherapy and radiation and more on the antitumor effects of the graft (called the graft‐versus‐tumor effect).