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Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) may be related to the occurrence of complications, including graft-versus-host disease (GvHD) and infections. The pathogenesis of acute GvHD is connected with T lymphocytes, which identify alloantigens on host's antigen-presenting cells, activate production of interferon-gamma (IFN-gamma) and interleukin-2 (IL-2), and act on the immune effector cells and damage tissues and organs.
Aim: The aim of the study was to investigate and distinguish serum concentration profiles of IFN-gamma and IL-2 within a 30-d period after allo-HSCT.
Methods: We enrolled 62 patients, , 30 (48%) male and 32 (52%) female subjects [median age 49.5 (19-68) years], after allo-HSCT from siblings ( = 12) or unrelated donors ( = 50) due to acute myeloid leukemia with myeloablative conditioning ( = 26; 42%) and with non-myeloablative conditioning ( = 36; 58%). All patients were given standard immunosuppressive therapy with cyclosporin-A and methotrexate and pre-transplant antithymocyte globulin in the unrelated setting. Blood samples were collected pre-transplant before and after (on day -1) the conditioning therapy and on days +2,+4, +6, +10, +20, and +30 after allo-HSCT. Serum levels of IL-2 and IFN-gamma were determined using ELISA.
Results: Patients were divided into four groups depending on the presence of acute GvHD and clinical manifestations of infection. Group I included patients with neither acute GvHD nor infections [ = 15 (24%)], group II consisted of patients with infections without acute GvHD [ = 17 (27%)], group III was comprised of patients with acute GvHD without infections [ = 9 (15%)], and group IV included patients with both acute GvHD and infections [ = 21 (34%)]. IFN-gamma concentrations were higher in Group II than in other groups on days +20 ( = 0.014) and +30 ( = 0.008). Post-hoc tests showed lower concentrations of IFN-gamma on day +30 in groups I ( = 0.039) and IV ( = 0.017) compared to group II. The levels of IL-2 were mostly undetectable.
Conclusion: Serum levels of IFN-gamma following allo-HSCT progressively escalate. High serum levels of IFN-gamma are related to infectious complications rather than acute GvHD. Serum concentrations of IL-2 in most patients are undetectable.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9521416 | PMC |
http://dx.doi.org/10.4331/wjbc.v13.i4.72 | DOI Listing |
Transplant Cell Ther
December 2024
Hematology/Oncology, The Hospital for Sick Children and the University of Toronto, Toronto, Ontario, Canada.
Background: Allogeneic transplant for patients with transfusion-dependent thalassemia is challenging once there has been iron overload and chronic transfusion support.
Objective(s): A transplant strategy that reduced intensity of the preparative regimen and tailored immunosuppression to both support donor engraftment and prevent GVHD was developed for this population. The combination of a pretransplant immunosuppression phase with reduced dosing of fludarabine/prednisone, treosulfan-based preparative regimen with reduced cyclophosphamide dosing, and introduction of a calcineurin/methotrexate-free GVHD prophylaxis/engraftment supporting regimen with abatacept/sirolimus/ATG was tested.
Transfus Apher Sci
December 2024
University of Health Sciences, Ankara Oncology Training and Research Hospital, Department of Hematology & Apheresis Unit, Ankara, Turkey; Ankara Yildirim Beyazit University, School of Medicine, Department of Internal Medicine, Division of Hematology, Ankara, Turkey.
Objective: Graft-versus-host disease (GvHD) is a common and serious complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT), significantly impacting transplant efficacy. In the treatment of GvHD, numerous therapeutic approaches have been explored, with mesenchymal stem cells (MSCs) emerging as a prominent immunomodulatory option. We aimed to evaluate efficacy and outcomes of using MSCs for steroid refractory acute GVHD (SR-aGvHD) management.
View Article and Find Full Text PDFiScience
December 2024
Toronto General Hospital Research Institute, Ajmera Transplant Centre, University Health Network, Toronto, ON M5G 1L7, Canada.
Natural killer (NK) cell activity is influenced by cytokines and microenvironment factors, resulting in remarkably diverse functions, by contributing to inflammatory responses or serving as rheostats of adaptive immunity. Using single cell RNA sequencing (scRNA-seq), we identified a CD56NK cell population associated with hematopoietic stem cell transplant recipients protected from acute graft-versus-host disease (GVHD). We further define a role for the combination of interleukin-2 (IL-2) and transforming growth factor β1 (TGF-β1) in promoting a regulatory phenotype in NK cells.
View Article and Find Full Text PDFTransfus Apher Sci
December 2024
University of Health Sciences, Ankara Oncology Training and Research Hospital, Department of Hematology & Apheresis Unit, Ankara, Turkey; Ankara Yildirim Beyazit University, School of Medicine, Department of Internal Medicine, Division of Hematology, Ankara, Turkey.
Background And Objectives: Following an allogeneic hematopoietic stem cell transplant (allo-HSCT), a primary cause of morbidity and mortality is still steroid-refractory acute graft-versus-host disease (SR-aGVHD). Recently, ruxolitinib, an oral inhibitor of JAK1 and JAK2, was approved for use in individuals suffering from SR-aGVHD. This study aimed to analyze the efficacy and toxicity of ruxolitinib in the real world.
View Article and Find Full Text PDFBlood Res
December 2024
Division of Hematology-Oncology, Hanyang University Seoul Hospital, Seoul, Republic of Korea.
Purpose: This study investigated the occurrence of subsequent malignancies (SM) in adult patients with severe aplastic anemia (SAA) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) to address the lack of large-scale, long-term data on this complication.
Methods: A retrospective cohort analysis of 376 adult patients with SAA who underwent allo-HSCT between 2002 and 2021 at a single center was conducted. The incidence, risk factors, and survival impact of SM were also examined.
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