THE VALUE OF EXTRACORPOREAL PHOTOCHEMOTHERAPY IN RENAL TRANSPLANT REJECTION INHIBITION

The aim of the study was to determine the value of extracorporeal photochemotherapy (EPCT) in the induction of tissue tolerance in renal transplantation. EPCT was applied to 24 renal transplant recipients in early postoperative period, the control group consisted of paired transplant recipients. In the group using EPCT over a three-year period of observation no clinical or histological signs of rejection were observed. In the control group, histologically confirmed rejection was observed in 4 cases, in 2 cases transplantectomy due to acute rejection. The reducing incidence of infectious complications in the study group compared with the control one (4 and 19 cases, respectively) and decreasing number of hospitalizations on various reasons (8 and 47 cases in the study and control groups, respectively) were also noted. Three-year graft survival was 100% and 83.3% in the study and the control groups, respectively. Using immunological tests in 30 days after transplantation the stable number of cells expressing coactivation molecules (57.7 ± 18.2 and 52.7 ± 23.2%, respectively, p > 0.05) and the density of their co-expression (22.7 ± 6.0 and 19.6 ± 7.0 units, respectively, p > 0.05) were demonstrated, while in the study group, the pronounced and statistically significant reduction both in the amount of cells expressing co-activation receptors (from 57.7 ± 18.2 to 34.5 ± 11.4%, p < 0.05) and in the density of these receptors on naive helper T-lymphocytes (from 22.7 ± 6.0 to 16.8 ± 5.1 units, p < 0.05) was revealed. Thus, it is noted that EPCT provides induction of tolerance to MHC antigens in kidney transplantation due to reducing expression of coactivation molecules which promote the second signaling pathway to T-cell receptor activation

APPLICATION OF EXTRACORPOREAL PHOTOCHEMOTHERAPY IN SKIN LYMPHOMAS AND TRANSPLANTATION OF SOLID ORGANS

The new immunotherapeutic method is presented in the review - an extracorporeal photochemotherapy. The questions concerning its application in the T-cellular lymphoma of skin and transplantation of solid bodies are discussed. The special attention is paid to the mechanism of its therapeutic action

Extracorporeal photopheresis in solid organ transplantation

Despite the use of up-to-date immunosuppressive agents, graft rejection episodes are quite common and pose a serious threat to thousands of solid organ recipients. Continuous use of various combinations of immunosuppressants cause serious complications, such as arterial hypertension, post-transplant diabetes mellitus, renal failure, increased risk of infections, malignant neoplasms, etc. The attempts to achieve the desired or forced minimization of the graft immunosuppression are associated with the threat of its rejection, which makes it necessary to search for less toxic, non-medical, immunological, including cellular, management methods. One of the promising methods based on cell technology is extracorporeal photopheresis (ECP). ECP is a well-established second line therapy recommended for the prevention and treatment of refractory rejection of a heart transplant. ECP improves the pulmonary allograft functioning in patients with treatment resistant obliterating bronchiolitis syndrome. However, its value as a preventive method has not yet been established. ECP effectiveness for induction, maintenance, or anti-crisis therapy in transplantation of kidney, liver or other solid organs has been rather convincing, but the lack of randomized multicenter studies limits its use. The optimal ECP strategy has not been yet established. Nevertheless, current understanding of the pathophysiological and immunological aspects of ECP is sufficient to develop a standard methodology and technology for the procedure, as well as for a quality control system for ECP in kidney and liver transplant recipients. The review discusses possible mechanisms of the immunomodulating effect of ECP. ECP is being increasingly studied in prospective randomized trials with larger samples. This allows for an extension of its clinical indications with clear criteria, as well as for studying its multifactorial underlying immunomodulating mechanism of action. Further research is needed to identify biomarkers that could predict ECP effectiveness in solid organ transplantation

Extracorporeal photopheresis in the treatment of the novel coronavirus disease COVID-19 (a case series)

Rationale: Most people infected with SARS-CoV-2 have asymptomatic or minor clinical manifestations and recover without any aggressive therapy. However, there are patient categories in need of specific treatment and those at high risk of severe disease. Control of viremia with antiviral therapy may not be the best therapeutic strategy, since, in addition to substantial toxicity, antiviral agents can suppress the production of antiviral antibodies and disintegrate adoptive immunity against SARS-CoV-2. Due to a high correlation between the symptoms severity in patients with COVID-19 and inflammation, anti-inflammatory corticosteroids have been proposed to treat the disease. However, clinical data do not support the systemic administration of corticosteroids for the treatment of patients with severe COVID-19. Such treatment may have a negative effect due to suppression of the adoptive immune system. In this regard, the development or use of already available of agents that modulate inflammation without compromising the adoptive immune response could be the most effective therapeutic strategy.Aim: To evaluate clinical efficacy and safety of the cell biotherapy technique, the extracorporeal photopheresis (ECP), in the treatment of patients with moderately severe new coronavirus disease COVID-19.Materials and methods: The study included four patients (three women and one man, age 42 to 60 years), with SARS-CoV-2 infection confirmed by gene amplification. All patients had CT-confirmed bilateral multisegmental viral pneumonia (grades > 2, i.e. with 25 to 60% involvement of the lungs). Prior to admission, all patients received antibiotics (azithromycin 500 mg daily and levo-floxacin / amoxicillin clavulanate 500 mg BID) and antipyretics for torpid fever of up to 38.5-39 °C. The outpatient treatment lasted for 8 to 14 days, with signs of progressive respiratory failure. In addition to the moderately severe and torpid course of viral pneumonia, three patients showed hematology test abnormalities, such as hypochromic anemia, leukopenia, leukopenia/lymphopenia, and moderate thrombocytopenia. Three patients had high C-reactive protein (CRP) levels. Inpatient treatment consisted of azithromycin 500 mg daily, levofloxacin 500 mg BID, hydroxychloroquine 200 mg BID, and low molecular weight heparin (enoxaparin 0.4 ml, 4000 anti-Xa IU, s.c. BID). Despite the treatment, the patients showed signs of progressive respiratory failure, with increasing dyspnea and gradual decrease in saturation from 96% to 92%. Isolation of peripheral blood mononuclear cells was done in an intermittent blood separator "Haemonetics MCS+” (USA), with subsequent cell irradiation with an extracorporeal blood irradiator (OKUFKE 320/400-600/650-01 "Yulia”, ZAO NPKF "METOM”, Russia). Ammifurin (ZAO "Pharmcenter VILAR”, Russia) was used as a photosensitizer. Three patients had two ECP sessions with an interval of 24 hours, and one patient had one ECP session.Results: In three patients who had received two ECP sessions, there was a regression of radiographic signs of viral pneumonia from CT2 to CT1 (less than 25% of lung tissue involvement) during the next four days (96 hours). In one patient, the follow-up CT showed resolving pneumonia with less than 5% involvement of the lungs. The patients (n = 3) with baseline high CRP levels showed their normalization at 4 days after two ECP sessions. At 24 hours after a single ECP session, leukocyte count and differential, as well as platelets were restored. In three patients, viral RNA tests within 2 to 4 days after ECP were negative. These results were associated with normalization of body temperature, no further progression of respiratory failure, and a reduction in hospital stay.Conclusion: The use of ECP in 4 patients with moderately severe SARS-CoV-2 infection has contributed to the rapid relief of clinical symptoms, resolution of the inflammation and restoration of respiratory abnormalities in all of them. These observations allow us to consider ECP as an effective and safe method of treatment for moderately severe COVID-19 and a promising adjuvant method in the high-risk patients in order to prevent an unfavorable disease outcome