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Oncotarget Jan 2017There are limited data on the safety and efficacy of immunotherapy for patients with advanced pancreatic cancer (APC). A meta-analysis of single-arm trials is proposed... (Comparative Study)
Comparative Study Meta-Analysis
There are limited data on the safety and efficacy of immunotherapy for patients with advanced pancreatic cancer (APC). A meta-analysis of single-arm trials is proposed to assess the efficacy and safety of immunotherapy for APC. Eighteen relevant studies involving 527 patients were identified. The pooled disease control rate (DCR), overall survival (OS), progression free survival (PFS), and 1-year survival rate were estimated as 59.32%, 7.90 months, 4.25 months, and 30.12%, respectively. Subgroup analysis showed that the pooled OS, PFS, and 1-year survival rate were significantly higher for autologous activated lymphocyte therapy compared with peptide-based vaccine therapy (OS: 8.28 months vs. 7.40 months; PFS: 6.04 months vs. 3.86 months; 1-year survival rate: 37.17% vs. 19.74%). Another subgroup analysis demonstrated that the pooled endpoints were estimated as obviously higher for immunotherapy plus chemotherapy compared with immunotherapy alone (DCR: 62.51% vs. 47.63%; OS: 8.67 months vs. 4.91 months; PFS: 4.91 months vs. 3.34 months; 1-year survival rate: 32.32% vs. 21.43%). Of the included trials, seven trials reported no treatment related adverse events , five trials reported (16.6 ± 3.9) % grade 3 adverse events and no grade 4 adverse events. In conclusion, immunotherapy is safe and effective in the treatment of APC.
Topics: Cancer Vaccines; Clinical Trials as Topic; Combined Modality Therapy; Disease-Free Survival; Drug Therapy; Humans; Immunotherapy; Lymphocyte Transfusion; Middle Aged; Pancreatic Neoplasms; Treatment Outcome
PubMed: 27992378
DOI: 10.18632/oncotarget.13968 -
The International Journal of... Apr 2019Infective endocarditis (IE) is a life-threatening disease, establishing a diagnosis is often challenging. The aim of this prospective study was to evaluate and compare... (Comparative Study)
Comparative Study
Infective endocarditis (IE) is a life-threatening disease, establishing a diagnosis is often challenging. The aim of this prospective study was to evaluate and compare the diagnostic performance of the combined use of single photon emission tomography and computed tomography with technetium99m-hexamethylpropyleneamineoxime-labeled leukocytes (99mTc-HMPAO-SPECT/CT) with transthoracic echocardiography (TTE) in patients with suspected IE. We enrolled 40 consecutive patients (12 females, 28 males, mean age: 58.6 ± 18) with suspected IE in the years 2015-2016. All patients underwent clinical evaluation, TTE and 99mTc-HMPAO-SPECT/CT for the assessment of lesions typical for IE. Scans were evaluated for the presence and location of increased radioactivity foci, corresponding to the accumulation of radiolabeled leukocytes in inflammatory lesions. After 6 months, the patients were re-evaluated clinically and with TTE. Final IE diagnosis was established in 14 (35%) patients. Lesions typical for IE were shown in 28 (70%) TTEs and 16 (40%) 99mTc-HMPAO-SPECT/CTs. The latter tests were characterized by 90% accuracy, 93% sensitivity, 88% specificity, 96% negative predictive value (NPV), 81% positive predictive value (PPV). TTE demonstrated 60% accuracy, 93% sensitivity, 42% specificity, 92% NPV, and 46% PPV. 99mTc-HMPAO-SPECT/CT was characterized by a lower number of false-positive results compared to TTE (3 vs. 15). In patients with suspected IE, 99mTc-HMPAO-SPECT/CT yields a smaller number of false-positive results, significantly higher diagnostic accuracy, specificity and PPV than TTE. It helps to differentiate IE infectious and sterile echocardiographic lesions and reduces by 27% the number of misdiagnosed IE classified in the 'possible IE' category by modified Duke Criteria.
Topics: Adult; Aged; Diagnosis, Differential; Echocardiography; Endocarditis; False Positive Reactions; Female; Humans; Leukocyte Transfusion; Male; Middle Aged; Predictive Value of Tests; Prospective Studies; Radiopharmaceuticals; Reproducibility of Results; Single Photon Emission Computed Tomography Computed Tomography; Technetium Tc 99m Exametazime; Time Factors
PubMed: 30382475
DOI: 10.1007/s10554-018-1487-x -
Blood Oct 2015In this issue of , Price et al report the results of a phase 3 prospective randomized trial comparing the clinical outcome of infected, severely neutropenic patients...
In this issue of , Price et al report the results of a phase 3 prospective randomized trial comparing the clinical outcome of infected, severely neutropenic patients after receiving or not receiving granulocyte transfusions.
Topics: Granulocytes; Humans; Infections; Leukocyte Transfusion; Neutropenia
PubMed: 26516218
DOI: 10.1182/blood-2015-09-669085 -
International Journal of Cell Cloning Jul 1986In mammalian ontogeny, the liver constitutes the primary hematopoietic organ for some time. Fetal liver cells (FLC) are rich in hematopoietic stem cells with a high... (Review)
Review
In mammalian ontogeny, the liver constitutes the primary hematopoietic organ for some time. Fetal liver cells (FLC) are rich in hematopoietic stem cells with a high proliferative potential but contain few post-thymic T cells. In animal studies, FLC restored hematopoiesis without severe graft-versus-host disease. However, genetic disparity between donor and host frequently limited durable engraftment and prevented or protracted complete immune reconstitution in most fully allogeneic recipients. Some children with severe combined immunodeficiency have been cured by FLC infusion, whereas favorable effects in aplastic anemia, acute leukemia, and inborn errors of metabolism have been limited and badly understood. Fetal liver transplantation in animals may serve as a model for the analysis and management of complications associated with the transfer of purified hematopoietic stem cell grafts and aid in the development of future therapeutic strategies requiring rapidly proliferating stem cell populations.
Topics: Anemia, Aplastic; Animals; Chimera; Fetus; Graft Survival; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Humans; Immunologic Deficiency Syndromes; Leukemia; Liver; Liver Transplantation; Lymphocyte Depletion; Lymphocyte Transfusion; Lymphocytes; Transplantation, Homologous
PubMed: 2875117
DOI: 10.1002/stem.5530040402 -
Acta Medica Portuguesa 1999Adoptive cellular immunotherapy with donor leukocytes of patients submitted to allogenic stem cell transplantation has had significant success in the past few years,... (Review)
Review
Adoptive cellular immunotherapy with donor leukocytes of patients submitted to allogenic stem cell transplantation has had significant success in the past few years, especially in the treatment of primary disease relapse and in the prevention and treatment of some post-transplant infectious complications. Most patients treated with donor leukocytes had a relapse of chronic myelogenous leukemia, which was successfully re-induced into remission. The most significant toxicities of this treatment are the development of graft versus host disease and marrow aplasia. Three strategies were developed to limit the former: the infusion of graded doses of donor leukocytes, the depletion of CD8+ cells and the transfer of donor leukocytes transvected with a timidine kinase gene, which renders these cells sensitive to gancyclovir. The post-transplant infectious complications treated successfully with donor leukocytes were Epstein-Barr virus-induced lymphoproliferative disorders and cytomegalovirus infection. The former, arising most frequently in recipients of unrelated and/or mismatched T-cell depleted grafts, were treated with donor unseparated leukocytes or Epstein-Barr virus-specific T-cells. Cytomegalovirus infection in the early post-transplant period was largely prevented by the infusion of virus-specific T-cell clones, which restored donor-specific immunity to cytomegalovirus in the recipient.
Topics: Animals; Blood Donors; Epstein-Barr Virus Infections; Graft vs Host Disease; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Immunotherapy, Adoptive; Leukocyte Transfusion; Transplantation, Homologous
PubMed: 10707463
DOI: No ID Found -
British Journal of Haematology Oct 2017Relapse is the main cause of treatment failure after allogeneic haematopoietic stem cell transplantation (allo-HSCT) for acute leukaemia (AL). Post-transplantation... (Review)
Review
Preventing relapse after haematopoietic stem cell transplantation for acute leukaemia: the role of post-transplantation minimal residual disease (MRD) monitoring and MRD-directed intervention.
Relapse is the main cause of treatment failure after allogeneic haematopoietic stem cell transplantation (allo-HSCT) for acute leukaemia (AL). Post-transplantation minimal residual disease (MRD) monitoring enables risk stratification and identifies AL patients at higher risk of relapse. MRD assessment primarily involves the determination of leukaemia-associated immunophenotypic patterns using multiparameter flow cytometry, and the polymerase chain reaction (PCR)-based evaluation of expression levels of leukaemia-related genes (specific reciprocal gene rearrangements and other mutation types). In addition, next generation sequencing and digital PCR may further enrich current MRD detection. Several MRD-directed interventions have demonstrated the ability to reduce the risk of relapse with acceptable treatment-related toxicities. Donor lymphocyte infusion (DLI) is the most important intervention for MRD-positive patients, while several modified strategies, such as granulocyte colony-stimulating factor-mobilized peripheral blood cells followed by short term immune suppression and escalating dose regimen, further improve the safety and efficacy of DLI. Interferon therapy, targeted drugs, and hypomethylating agents have also been introduced for MRD-directed interventions. Referring to the issues of whether and who would benefit from pre-emptive intervention according to MRD, in this review, we summarized this rapidly evolving area of MRD monitoring and MRD-directed interventions in AL patients after allo-HSCT.
Topics: Acute Disease; Allografts; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppression Therapy; Leukemia; Lymphocyte Transfusion; Monitoring, Physiologic; Neoplasm, Residual; Polymerase Chain Reaction; Recurrence
PubMed: 28542711
DOI: 10.1111/bjh.14778 -
Blood Jun 2000The primary limitations of granulocyte transfusions include low component cell dose and leukocyte incompatibility. Component cell dose improved with granulocyte...
Effect of leukocyte compatibility on neutrophil increment after transfusion of granulocyte colony-stimulating factor-mobilized prophylactic granulocyte transfusions and on clinical outcomes after stem cell transplantation.
The primary limitations of granulocyte transfusions include low component cell dose and leukocyte incompatibility. Component cell dose improved with granulocyte colony-stimulating factor (G-CSF) mobilization, and the transfusion of G-CSF-mobilized, human leukocyte antigen (HLA)-matched granulocyte components resulted in significant, sustained absolute neutrophil count (ANC) increments. However, the effect of leukocyte compatibility on outcomes with G-CSF-mobilized granulocyte transfusions is unclear. The objectives were to determine the effect of leukocyte compatibility on ANC increments and selected clinical outcomes after transfusion of prophylactic, G-CSF-mobilized granulocyte components into neutropenic recipients of autologous peripheral blood stem cell (PBSC) transplants. Beginning on transplant day 2, 23 evaluable recipients were scheduled to receive 4 alternate-day transfusions of granulocyte components apheresed from a single donor given G-CSF. G-CSF was also given to recipients after transplantation. Recipient ANC was determined before and sequentially after each granulocyte transfusion to determine the peak ANC increment. Leukocyte compatibility was determined at study entry only by a lymphocytotoxicity screening assay (s-LCA) against a panel of HLA-defined cells. Eight recipients had positive s-LCA. On days 2 and 4, the mean peak ANC increments after granulocyte transfusion were comparable between the cohorts with positive and negative s-LCA. However, the mean peak ANC increments on day 6 (246/microL vs 724/microL; P =.05) and day 8 (283/microL vs 1079/microL; P =.06) were lower in the cohort with positive s-LCA, in spite of the transfusion of comparable component cell doses. Adverse reactions occurred with only 5 of 87 (5.7%) granulocyte transfusions and were not associated with leukocyte compatibility test results. Platelet increments, determined 1 hour after granulocyte transfusion, were comparable between the cohorts. Although the 2 cohorts received PBSC components with similar CD34(+) cell doses, the cohort with a positive s-LCA had delayed neutrophil engraftment and a greater number of febrile days and required more days of intravenous antibiotics and platelet transfusions. Leukocyte incompatibility adversely affected ANC increments after the transfusion of G-CSF-mobilized granulocyte components and clinical outcomes after PBSC transplantation.
Topics: ABO Blood-Group System; Adolescent; Adult; Aged; Blood Donors; Female; Granulocyte Colony-Stimulating Factor; Granulocytes; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Histocompatibility Testing; Humans; Leukapheresis; Leukocyte Count; Leukocyte Transfusion; Male; Middle Aged; Neutrophils; Nuclear Family; Treatment Outcome
PubMed: 10828051
DOI: No ID Found -
Medical Science Monitor : International... Apr 2016BACKGROUND Concentrated leukocytes in leukocyte- and platelet-rich plasma (L-PRP) may deliver increased levels of pro-inflammatory cytokines to activate the NF-κB... (Comparative Study)
Comparative Study
BACKGROUND Concentrated leukocytes in leukocyte- and platelet-rich plasma (L-PRP) may deliver increased levels of pro-inflammatory cytokines to activate the NF-κB signaling pathway, to counter the beneficial effects of growth factors on osteoarthritic cartilage. However, to date no relevant studies have substantiated that in vivo. MATERIAL AND METHODS Autologous L-PRP and pure platelet-rich plasma (P-PRP) were prepared, measured for componential composition, and injected intra-articularly after 4, 5, and 6 weeks post-anterior cruciate ligament transection. Caffeic acid phenethyl ester (CAPE) was injected intraperitoneally to inhibit NF-κB activation. All rabbits were sacrificed after 8 weeks postoperative. Enzyme-linked immunosorbent assays were performed to determine interleukin 1β (IL-1β) and prostaglandin E2 (PGE2) concentrations in the synovial fluid, Indian ink staining was performed for gross morphological assessment, and hematoxylin and eosin staining and toluidine blue staining were performed for histological assessment. RESULTS Compared with L-PRP, P-PRP injections achieved better outcomes regarding the prevention of cartilage destruction, preservation of cartilaginous matrix, and reduction of IL-1β and PGE2 concentrations. CAPE injections reversed the increased IL-1β and PGE2 concentrations in the synovial fluid after L-PRP injections and improved the outcome of L-PRP injections to a level similar to P-PRP injections, while they had no influence on the therapeutic efficacy of P-PRP injections. CONCLUSIONS Concentrated leukocytes in L-PRP may release increased levels of pro-inflammatory cytokines to activate the NF-κB signaling pathway, to counter the beneficial effects of growth factors on osteoarthritic cartilage, and finally, result in a inferior efficacy of L-PRP to P-PRP for the treatment of osteoarthritis.
Topics: Animals; Cytokines; Dinoprostone; Female; Interleukin-1beta; Leukocyte Transfusion; NF-kappa B; Osteoarthritis, Knee; Platelet Transfusion; Platelet-Rich Plasma; Rabbits; Random Allocation; Synovial Fluid
PubMed: 27086145
DOI: 10.12659/msm.898218 -
Frontiers in Immunology 2024Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative therapy for many hematologic malignancies as well as non-malignant conditions. Part... (Review)
Review
Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative therapy for many hematologic malignancies as well as non-malignant conditions. Part of the curative basis underlying HSCT for hematologic malignancies relies upon induction of the graft versus leukemia (GVL) effect in which donor immune cells recognize and eliminate residual malignant cells within the recipient, thereby maintaining remission. GVL is a clinically evident phenomenon; however, specific cell types responsible for inducing this effect and molecular mechanisms involved remain largely undefined. One of the best examples of GVL is observed after donor lymphocyte infusions (DLI), an established therapy for relapsed disease or incipient/anticipated relapse. DLI involves infusion of peripheral blood lymphocytes from the original HSCT donor into the recipient. Sustained remission can be observed in 20-80% of patients treated with DLI depending upon the underlying disease and the intrinsic burden of targeted cells. In this review, we will discuss current knowledge about mechanisms of GVL after DLI, experimental strategies for augmenting GVL by manipulation of DLI (e.g. neoantigen vaccination, specific cell type selection/depletion) and research outlook for improving DLI and cellular immunotherapies for hematologic malignancies through better molecular definition of the GVL effect.
Topics: Humans; Transplantation, Homologous; Lymphocyte Transfusion; Graft vs Host Disease; Hematologic Neoplasms; Lymphocytes; Leukemia
PubMed: 38558819
DOI: 10.3389/fimmu.2024.1328858 -
Journal of Leukocyte Biology Jun 2022The use of mature neutrophil (granulocyte) transfusions for the treatment of neutropenic patients with invasive fungal infections (IFIs) has been the focus of multiple...
The use of mature neutrophil (granulocyte) transfusions for the treatment of neutropenic patients with invasive fungal infections (IFIs) has been the focus of multiple clinical trials. Despite these efforts, the transfusion of mature neutrophils has resulted in limited clinical benefit, likely owing to problems of insufficient numbers and the very short lifespan of these donor cells. In this report, we employed a system of conditionally immortalized murine neutrophil progenitors that are capable of continuous expansion, allowing for the generation of unlimited numbers of homogenous granulocyte-macrophage progenitors (GMPs). These GMPs were assayed in vivo to demonstrate their effect on survival in 2 models of IFI: candidemia and pulmonary aspergillosis. Mature neutrophils derived from GMPs executed all cardinal functions of neutrophils. Transfused GMPs homed to the bone marrow and spleen, where they completed normal differentiation to mature neutrophils. These neutrophils were capable of homing and extravasation in response to inflammatory stimuli using a sterile peritoneal challenge model. Furthermore, conditionally immortalized GMP transfusions significantly improved survival in models of candidemia and pulmonary aspergillosis. These data confirm the therapeutic benefit of prophylactic GMP transfusions in the setting of neutropenia and encourage development of progenitor cellular therapies for the management of fungal disease in high-risk patients.
Topics: Animals; Candidemia; Cell- and Tissue-Based Therapy; Invasive Fungal Infections; Leukocyte Transfusion; Mice; Neutropenia; Neutrophils; Pulmonary Aspergillosis
PubMed: 35355310
DOI: 10.1002/JLB.4HI1221-722R