Hematopoietic stem cell transplantation (HSCT) is a curative option for children with high-risk acute lymphoblastic leukemia (ALL). This retrospective single-center study analyzed 236 pediatric ALL patients in complete remission who underwent allogeneic HSCT using ex-vivo T cell depletion between 2012 and 2021. The majority received haploidentical grafts (n = 202), while the remainder received matched unrelated donor (MUD) grafts (n = 34). At four years, event-free survival (EFS) and overall survival (OS) were 57
INTRODUCTION:Extracorporeal photopheresis (ECP) is an attractive treatment for graft-versus-host disease (GVHD) following allogeneic hematopoietic stem cell transplantation due to the lack of systemic immunosuppression. Modifications of ECP without leukapheresis are being actively studied in clinical practice around the world. A low-volume method of extracorporeal photochemotherapy-micro-ECP-has been developed at the Rogachev Federal Scientific and Clinical Centre of Pediatric Hematology, Oncology and Immunology. We present the results of using micro-ECP to treat acute and chronic GVHD. PATIENTS AND METHODS:We analyzed the treatment outcomes of 9 cases of acute GVHD and 15 cases of chronic GVHD using micro-ECP for the period from April 2021 to March 2024. The cellular product was obtained by collecting 20-30 mL of whole blood followed by photochemical treatment. The processed autologous cell product was administered to the patient. RESULTS:The overall response rate in patients diagnosed with acute GVHD was 44%, while the organ-specific response rate was 56% for skin and 40% for gastrointestinal. The steroid-sparing effect for acute GVHD was 89%. In the treatment of chronic GVHD, the overall response rate was 73.3%. The organ-specific response rate was 71% for skin, 67% for gastrointestinal, 67% for lung, 100% for eyes, and 100% for liver chronic GVHD. The steroid-sparing effect for chronic GVHD was 63%. CONCLUSION:In the treatment of acute and chronic GVHD, micro-ECP has demonstrated promising efficacy. Although the method remains experimental, it is already apparent that micro-ECP constitutes an attractive alternative to standard ECP when leukapheresis is not a viable option.
Extracorporeal photopheresis (ECP) has proven effective in the treatment of several diseases, including acute and chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation. In its standard version, ECP requires leukapheresis to obtain a fraction of mononuclear cells. The possibility of using leukapheresis is limited by the requirements for vascular access and the somatic status of the patient. In the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Ministry of Health of Russia was developed a new ECP method that does not require leukapheresis. This paper presents a description of two clinical cases of severe refractory GVHD treated by micro-ECP.
Introduction. Pathogen reduction technologies (PRT) in donor blood components have become a new milestone in ensuring the safety of transfusions. However, it is widely acknowledged that the use of PRT can compromise the quality of blood components and potentially diminish the efficiency of transfusion. The purpose of this retrospective analysis is the presentation of the results of the use of pathogenic-reduced components of donor blood in comparison with standard transfusion practice in hematopoietic stem cell transplantation (HSCT) recipients. Materials and methods . An analysis was conducted of the results of transfusions to recipients of allogeneic HSCT performed in 2018–2022. We presented results of 1901 red blood cell transfusions (1848 of which were gamma-irradiated and 53 were pathogen-reduced), 8192 platelet concentrates transfusions (7654 of which were gamma-irradiated and 538 were pathogen-reduced) and donor plasma transfusions (freshly frozen plasma (FFP) – 1381, pathogen-reduced – 169). Results. The estimated laboratory efficiency of the transfusion of pathogen-reduced red blood cells was comparable to that of gamma-irradiated. Platelet concentrates subjected to pathogen reduction, as well as those prepared using an additional solution, demonstrated the lowest results of post-transfusion increase compared to gamma-irradiated platelet concentrates. Plasma processed using the pathogen reduction method resulted in a smaller increase in fibrinogen concentration. All other hemostasis indices were comparable to those of FFP. Conclusion. The clinical use of pathogen-reduced donor blood components is an effective transfusion practice, but further improvements in TRP are needed.
Introduction . Pathogen reduction technologies in donor blood products have provided a preventive approach against a variety of hemotransmissive infections as well as prevention of donor leukocyte complications. However, while pathogen reduction in plasma and platelet concentrates is currently widespread, methods for reducing pathogens in red blood cell (RBC)-containing products are still being studied. Aim : to analyze the transfusion results of a pathogen-reduced RBC suspension in patients with various oncological and hematological diseases as well as defects of the immune system in order to prevent transfusion transmission of cytomegalovirus infection. Patients and methods . The results of transfusion therapy of a pathogen-reduced RBC suspension for the prevention of transfusion transmission of CMV infection in 27 patients who underwent transfusions during a long follow-up period are presented. Results . A total of 27 patients received 167 transfusions of pathogen-reduced RBC suspension. Transfusion efficacy, assessed by hemoglobin increase, was dependent on the transfusion volume per body weight, but was independent of the storage time of the RBC suspension over the measured interval. The transfusions were effective and tolerated without complications. Conclusion . The clinical use of pathogen-reduced RBC suspension is safe and provides sufficient clinical and laboratory efficacy.
Introduction. Extracorporeal photopheresis (ECP) is an attractive method of treating graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation due to the lack of systemic immunosuppression. However, the clinical use of ECP is often limited by the need for leukapheresis. There are modifications of ECP without the use of leukapheresis, in particular low-volume ECP.Aim: to analyze the use of lv-ECP for the treatment of patients with acute and chronic GvHD.Patients and methods. The results of treatment of 9 cases of acute GVHD and 15 cases of chronic GVHD using the lv-ECP from April 2021 to March 2024 are presented. The cellular product was obtained by effusion of 15-30 ml of whole blood followed by photochemical treatment. The processed autologous cell product was administered to the patient.Results. The overall response in patients with acute GVHD was 44%, organ-specific response for skin lesions was 56 %, and for gastrointestinal lesions, 40%. In the treatment of chronic GvHD, the overall response was 73.3 %; the effectiveness of therapy for skin lesions was 71 %; for gastrointestinal lesions 67 %; for lung damage 67 %; for eye damage 100 %, for liver damage 100 %.Conclusion. lv-ECP has shown promising efficacy results in the treatment of acute and chronic GvHD. lv-ECP is an attractive alternative to standard ECP when leukapheresis is not possible.
Graft-versus-host disease (GVHD) is one of the main complications of allogeneic hematopoietic stem cell transplantation. A large number of patients do not respond to corticosteroid therapy and require alternative treatment options. Extracorporeal photopheresis (ECP) is an empirically developed cell therapy that has proven effective in the treatment of both acute and chronic GVHD. Because ECP is safe to use and has few serious side effects, its application in the management of GVHD is very attractive. The purpose of this paper is to present a literature review on the use of ECP for the treatment of GVHD.
Extracorporeal photopheresis (ECP) has proven effective in the treatment of several diseases, including acute and chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation. In its standard version, ECP requires leukapheresis to obtain a fraction of mononuclear cells. The possibility of using leukapheresis is limited by the requirements for vascular access and the somatic status of the patient. We have developed a new ECP method that does not require leukapheresis. This paper presents a description of two clinical cases of severe refractory GVHD treated by micro-ECP.
Surgery in cancer patients may sometimes involve significant blood loss, and intraoperative red blood cell salvage is an effective technique that can reduce postoperative complications. Autologous reinfusion of red blood cells processed by a cell saver machine significantly reduces the number of red blood cell transfusions from donors. The use of leukocyte filters eliminates the possibility of tumor cell release into the patient’s circulation. This method is easy to use, however medical staff should be appropriately trained in cell salvage. Intraoperative red blood cell salvage can and should be used in the management of patients undergoing planned or emergency surgeries with expected blood loss > 500 mL.
Extracorporeal photopheresis is a method of cell therapy that was developed and introduced into clinical practice of various specialties over 30 years ago but its mechanism of action, clinical application and the possibility of further modification are still on the minds of scientists around the world. Here we provide a review of the existing literature on the major critical aspects of the extracorporeal photopheresis technology as well as information on possible ways of modifying the method, the current understanding of its mechanism of effectiveness, the use in various diseases and pathological conditions and a list of possible side effects.
Implementation of the technique of immunomagnetic selection requires the procurement of a large number of CD34+ cells from haploidentical donors within a single apheresis procedure. The release of stem cells with granulocyte colony‐stimulating factor (G‐CSF) alone is unsatisfactory in a number of donors, and plerixafor, a CXCR4 chemokine receptor antagonist, could be used as an additional mobilization agent. The aim of our study was to examine whether a lower dose of plerixafor (0.12 mg/kg) can provide sufficient increase in CD34+ cells in the peripheral blood of allogeneic healthy donors in comparison with a historical control group. In addition, we assessed the risk of inability to provide the recipient with a transplant containing the optimal dose of 8–10 × 106 CD34+ cells/kg body weight of the recipient.
Early complications of hematopoietic stem cell transplantation (HSCT) of vascular origin within the first 30-60 days after HSCT, which are resulting from endothelial injury, are an important cause of transplant-associated morbidity and mortality. Authors describe a case report serving as an example of several endothelial syndromes development with overlapping clinical features. Risk factors and therapy approaches of these complications are discussed.
In the observational clinical study, we identified the oxidative markers of HPV-associated cervical carcinogenesis and the local/circulating ligands of TNF-alpha-induced apoptosis. Cervical biopsies of 196 females infected with low-cancer-risk HPV10/13 or high-cancer-risk HPV16/18 (healthy, pre-cancerous CIN I and CIN II, and CIN III carcinoma) were analysed for OH radical scavenging, catalase, GSH-peroxidase, myeloperoxidase (MPO), nitrate/nitrite, nitrotyrosine, and isoprostane. Ligands of TNF-alpha-dependent apoptosis (TNF-alpha, TRAIL, IL-2, and sFAS) were determined in cervical fluid, biopsies, and serum. Cervical MPO was highly enhanced, while nitrotyrosine decreased in CIN III. Local/circulating TRAIL was remarkably decreased, and higher-than-control serum TNF-alpha and IL-2 levels were found in the CIN I and CIN III groups. Then, 250 females infected with HPV16/18 (healthy and with CIN I and CIN II) were recruited into a placebo-controlled clinical study of supplementation with fermented mangosteen (FM, 28g/day, daily) for three months. Post-trial colposcopy revealed normal patterns in 100% of the FM group versus 62% of the placebo group. Inflammatory cells in cervical fluid were found in 21% of the FM group versus 40% of the placebo group. Locally, FM drastically diminished MPO and NO2/NO3, while it remarkably increased TRAIL. Additionally, FM supplementation normalised serum TRAIL, TNF-alpha, and IL-2.
Epstein–Barr virus (EBV) is a member of herpes-viruses family. Now it is well-known, that it can be a cause of wide spectrum lymphoproliferative disoders. The given problem is especially serious after hematopoietic stem cells transplantation (HSCT); frequency of death linked to this complication can achieve 50–90 %. Risk factors for development of posttransplant lymphoproliferative syndromes (PTLS) are: using partially compatible graft, T-cell depletion, presence of severe acute graft-versus-host reaction (GVHD), using of antitymocytic globulin, etc. Severity of associated with EBV posttransplant complications and problems relate to absence of clear diagnostic algorithm, PTLS prophylactic and therapy schedule are argument for necessity of the further studies.
Food supplements based on fermented Carica papaya and Morinda citrifolia, known for their immune modulating, redox balancing, and anti-inflammatory effects, were added to conventional treatment protocols prescribed to patients recovering after severe and moderate COVID-19 disease in order to alleviate long-lasting post-COVID symptoms. A randomized single-center placebo-controlled clinical laboratory study was designed and performed (total number of participants 188, with delta variant of virus 157, with omicron 31). Clinical statuses were assessed using computer tomography, electrocardiography, a questionnaire, and physical endurance. Plasma cytokines (IL-6, IL-8, IL-17A, and INF-gamma), nitrate/nitrite ratio, antioxidant activity (AOA), and polymorphonuclear leukocyte (PMN) ATP levels were determined before and 20 days following the addition of 28 g of fermented supplements twice per day. The capacity of PMN to phagocyte and the oral-nasal-pharyngeal microbiota were assessed. Clinical symptoms, IL-6, IL-8, and nitric oxide metabolites diminished significantly compared to the placebo group and their background expression. The PMN capacity to phagocyte, AOA, and ATP content remarkably increased. The oral-nasal-pharyngeal microbiota were unchanged. On these grounds, we suggest that fermented tropical fruits could efficiently diminish post-COVID clinical symptoms through several immune-modulating, redox balancing, and pro-energy mechanisms.
Cytomegalovirus infection (CMV) is an extremely serious problem in patients after hematopoietic stem cells transplantation (HSCT). We have evaluated importance of major risk factors CMV development in patients after allogeneic HSCT (n = 168) from related (n = 56), unrelated (n = 90) or haploidentical donors (n = 22). Clinical importance of HSCT type as risk factors CMV development was shown; patients after unrelated or haploidentical HSCT had the worst prognosis. We also demonstrated that ≥ 2 grade acute GVHD statistically significant increase CMV reactivation probability after any types of HSCT. Comparison of infection reactivation frequency and event-free survival between subgroups of patients, received HSCT from CMV-positive and CMV-negative donors, absence of any differences was revealed. In the second group CMV infection was more severe. Preventive gancyclovir treatment has not shown efficacy and any influence on frequency of CMV reactivation.
Extracorporeal photopheresis (ECP) has proven effectiveness for treatment of several diseases, including acute and chronic graft-versus-host disease (GVHD) after allogenic transplantation of hematopoietic blood stem cells. The standard ECP requires leukapheresis to obtain a mononuclear cell fraction. The possibility of using leukapheresis is limited by the requirements for vascular access and the somatic status of the patient. There is a relatively new method of performing ECF, called «mini-photopheresis» (mini-ECF), in which a fraction of mononuclear cells is isolated from a dose of whole blood obtained by the exfusion method. The article presents preliminary results of using mini-ECP in patients with acute and chronic GVHD. Materials and methods of research: the study included 11 patients with acute (7 patients) and chronic (4 patients) GVHD who received mini-ECP therapy from June 2018 to January 2021. Leukocyte fractions rich in mononuclear cells were prepared from the dose of whole blood of patients. The resulting fraction was diluted with 0,9% NaCl solution to less than 3% hematocrit. The cellular product was then injected with an 8-Methoxyperalene and programmed with UV spectrum A. Autologous erythrocytes and the finished cellular product were injected into the patient after irradiation. Results: 6 out of 7 patients (85,7%) with acute GVHD has responded to mini-ECP therapy. In patients with chronic GVHD, the response rate to mini-ECP therapy was 25%. In both groups there are no significant differences found in the number of leukocytes count per body mass in the finished cellular product. The correlation between the presence and severity of response to mini-ECP therapy with the number of leukocytes in the finished cellular product was not determined. None of the patients had adverse reactions and complications associated with mini-ECP therapy. Conclusion: mini-ECP is an attractive alternative for treatment of patients with steroid-resistant or steroid-dependent GVHD who cannot undergo leukapheresis. Our results are preliminary, but promising. We will continue to use this method as a second-line therapy for patients with contraindications to leukapheresis.