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Transplantation May 2020With the development of modern solid-phase assays to detect anti-HLA antibodies and a more precise histological classification, the diagnosis of antibody-mediated... (Review)
Review
With the development of modern solid-phase assays to detect anti-HLA antibodies and a more precise histological classification, the diagnosis of antibody-mediated rejection (AMR) has become more common and is a major cause of kidney graft loss. Currently, there are no approved therapies and treatment guidelines are based on low-level evidence. The number of prospective randomized trials for the treatment of AMR is small, and the lack of an accepted common standard for care has been an impediment to the development of new therapies. To help alleviate this, The Transplantation Society convened a meeting of international experts to develop a consensus as to what is appropriate treatment for active and chronic active AMR. The aim was to reach a consensus for standard of care treatment against which new therapies could be evaluated. At the meeting, the underlying biology of AMR, the criteria for diagnosis, the clinical phenotypes, and outcomes were discussed. The evidence for different treatments was reviewed, and a consensus for what is acceptable standard of care for the treatment of active and chronic active AMR was presented. While it was agreed that the aims of treatment are to preserve renal function, reduce histological injury, and reduce the titer of donor-specific antibody, there was no conclusive evidence to support any specific therapy. As a result, the treatment recommendations are largely based on expert opinion. It is acknowledged that properly conducted and powered clinical trials of biologically plausible agents are urgently needed to improve patient outcomes.
Topics: Antilymphocyte Serum; Consensus; Graft Rejection; Humans; Immunosuppression Therapy; Isoantibodies; Kidney Transplantation; Societies, Medical; Tissue Donors
PubMed: 31895348
DOI: 10.1097/TP.0000000000003095 -
American Journal of Orthodontics and... Sep 2019
Topics: Antilymphocyte Serum; Data Collection; Kidney Transplantation; Sensitivity and Specificity
PubMed: 31474255
DOI: 10.1016/j.ajodo.2019.06.006 -
[Rinsho Ketsueki] the Japanese Journal... Feb 2016Idiopathic aplastic anemia (AA) is an autoimmune disease caused by T cells. An increase in the percentage of glycosylphosphatidylinositol-anchored protein-deficient... (Review)
Review
Idiopathic aplastic anemia (AA) is an autoimmune disease caused by T cells. An increase in the percentage of glycosylphosphatidylinositol-anchored protein-deficient cells and the presence of HLA allele-lacking leukocytes due to 6pUPD provide indirect evidence that T cells contribute to the pathophysiology of AA. Recent studies have revealed the presence of somatic mutations in MDS and/or AML candidate genes in one third of AA patients. Current treatment topics include the efficacy of eltrombopag for AA found to be refractory to immunosuppressive therapy as well as for newly diagnosed AA when administered in combination with ATG and cyclosporine. Furthermore, improved outcomes of allogeneic bone marrow transplantation from unrelated donors using reduced-intensity conditioning regimens have been obtained with eltrombopag. Fludarabine-based regimens are now the mainstream approach for preconditioning and have lowered the transplant-related mortality rate. However, new problems such as mixed chimerism and secondary graft failure have arisen. Attempts to prevent GVHD more efficiently by including ATG and alemtuzumab in the preconditioning regimen are being investigated.
Topics: Alemtuzumab; Anemia, Aplastic; Animals; Antibodies, Monoclonal, Humanized; Antilymphocyte Serum; Bone Marrow Transplantation; Humans; Immunosuppressive Agents; Transplantation Conditioning
PubMed: 26935624
DOI: 10.11406/rinketsu.57.91 -
Leukemia Dec 2023Non-severe aplastic anemia is a rare bone marrow failure disorder characterized by variable degrees and combination of cytopenias, with limited data on management and... (Observational Study)
Observational Study
Non-severe aplastic anemia is a rare bone marrow failure disorder characterized by variable degrees and combination of cytopenias, with limited data on management and outcome. We describe a large multicentric series of 259 patients, focusing on clinical and molecular features, treatment, evolution, and survival. The majority required treatment with cyclosporine (CyA) alone (N = 84) or in combination with anti-thymocyte globulin (ATG,44) or eltrombopag (20), eltrombopag alone (10), or others (25) including androgens. Similar outcomes were observed across different strategies, with a 6-month overall response rate of 73% for CyA, 74% for ATG plus CyA, 68% for CyA plus eltrombopag, 87% for eltrombopag, and 79% for others. Notably, 56 patients (39%), mainly receiving CyA plus eltrombopag, achieved a trilineage response (p = 0.02). Progression to myeloid neoplasms was limited (8%) and not related to mutational status. Hemolytic PNH developed in 10% of cases, being predicted by detection of small clones at diagnosis. Survival was negatively impacted by age, male gender, LDH, platelets/erythrocyte transfusion need, and somatic mutations by NGS, and positively by higher neutrophils at diagnosis, PNH clones, and trilineage response at 6 and 12 months. Multivariable analysis confirmed the detrimental role of age and the favorable association with PNH clone and trilineage response at 6 months.
Topics: Humans; Male; Infant; Anemia, Aplastic; Cyclosporine; Antilymphocyte Serum; Benzoates; Immunosuppressive Agents; Treatment Outcome
PubMed: 37794100
DOI: 10.1038/s41375-023-02047-z -
Diabetes Jun 2019
Topics: Animals; Antilymphocyte Serum; Bariatric Surgery; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Fibroblast Growth Factors; Hepatic Artery; Humans; Hyperuricemia; Liver; Obesity; Sympathectomy
PubMed: 31109938
DOI: 10.2337/db19-ti06 -
American Journal of Transplantation :... Aug 2017
Topics: Antilymphocyte Serum; CD4-Positive T-Lymphocytes; Cross Reactions; Humans; Lymphopenia
PubMed: 28544604
DOI: 10.1111/ajt.14370 -
Blood Reviews Nov 2023Allogenic hematopoietic stem cell transplantation (allo-HSCT) is the most important therapeutic option for hematological disorders, although graft-versus-host disease... (Review)
Review
Allogenic hematopoietic stem cell transplantation (allo-HSCT) is the most important therapeutic option for hematological disorders, although graft-versus-host disease (GVHD) remains the main cause of mortality. Post-transplantation cyclophosphamide (PTCY) induces immune tolerance and is associated with a low incidence of GVHD and non-relapse mortality. Therefore, PTCY has emerged as a safe and effective GVHD prophylaxis in haploidentical transplantation and has been expanded to matched related or unrelated donor and mismatched unrelated donor HSCT. On the basis of current understanding of the mechanisms of PTCY and antithymocyte globulin (ATG) in the prevention of GVHD, growing evidence suggests that the combination of ATG and PTCY could improve allo-HSCT clinical outcomes. Further research will focus on optimizing PTCY regimens by modifying the timing of administration or adding other immunosuppressive agents.
Topics: Humans; Cyclophosphamide; Immunosuppressive Agents; Hematopoietic Stem Cell Transplantation; Graft vs Host Disease; Antilymphocyte Serum
PubMed: 37031067
DOI: 10.1016/j.blre.2023.101078 -
F1000Research 2020Aplastic anemia (AA) in its severe form has historically been associated with high mortality. With limited supportive care and no effective strategy to reverse marrow... (Review)
Review
Aplastic anemia (AA) in its severe form has historically been associated with high mortality. With limited supportive care and no effective strategy to reverse marrow failure, most patients diagnosed with severe AA (SAA) died of pancytopenia complications. Since the 1970s, hematopoietic stem cell transplantation (HSCT) and immunosuppressive therapy (IST) have changed SAA's natural history by improving marrow function and pancytopenia. Standard IST with horse anti-thymocyte globulin plus cyclosporine produces a hematologic response rate of 60 to 70%. In the long term, about one-third of patients relapse, and 10 to 15% can develop cytogenetic abnormalities. Outcomes with either HSCT or IST are similar, and choosing between these modalities relies on age, availability of a histocompatible donor, comorbidities, and patient preference. The introduction of eltrombopag, a thrombopoietin receptor agonist, improved SAA outcomes as both salvage (second-line) and upfront therapy combined with IST. As a single agent, eltrombopag in doses up to 150 mg daily improved cytopenias in 40 to 50% in those who failed initial IST, which associated with higher marrow cellularity, suggesting a pan-stimulatory marrow effect. When eltrombopag was combined with IST as upfront therapy, overall (about 90%) and complete responses (about 50%) were higher than observed extensively with IST alone of 65% and 10%, respectively. Not surprisingly, given the strong correlation between hematologic response rates and survival in SAA, most (>90%) were alive after a median follow-up of 18 months. Longer follow-up and real-word data continue to confirm the activity of this agent in AA. The use of eltrombopag in different combinations and doses are currently being explored. The activity of another thrombopoietin receptor agonist in AA, romiplostim, suggests a class effect. In the coming years, the mechanisms of their activity and the most optimal regimen are likely to be elucidated.
Topics: Anemia, Aplastic; Animals; Antilymphocyte Serum; Cyclosporine; Hematopoietic Stem Cell Transplantation; Horses; Humans; Immunosuppressive Agents; Salvage Therapy
PubMed: 32953089
DOI: 10.12688/f1000research.22214.1 -
Seminars in Hematology Apr 2016Haploidentical stem cell transplantation (haplo-SCT) with an anti-thymocyte globulin (ATG) preparative regimen is associated with induced immune tolerance, rapid... (Review)
Review
Haploidentical stem cell transplantation (haplo-SCT) with an anti-thymocyte globulin (ATG) preparative regimen is associated with induced immune tolerance, rapid hematopoietic recovery, effective prevention of graft-versus-host disease (GVHD), and lower non-relapse mortality (NRM). This has become a common and successfully applied protocol in patients with hematological diseases undergoing haplo-SCT. Survival rates among patients who undergo unmanipulated haploidentical blood and marrow transplantation (HBMT) with anti-thymocyte globulin (ATG)-based regimens are comparable to those following human leukocyte antigen (HLA)-matched sibling transplantation or unrelated donor transplantation. Unmanipulated HBMT can also be successfully used as a post-remission treatment algorithm for acute lymphoblastic leukemia (ALL) and adult acute myeloid leukemia (AML) in cases with unfavorable cytogenetics. Future investigations should focus on further improving donor selection, optimizing allografts, dealing with primary graft failure, and relapse prophylaxis and treatment.
Topics: Antilymphocyte Serum; Haploidy; Hematologic Diseases; Hematopoietic Stem Cell Transplantation; Humans; Stem Cell Transplantation; Transplantation, Homologous; Treatment Outcome
PubMed: 27000731
DOI: 10.1053/j.seminhematol.2016.01.004 -
Transplant Immunology Aug 2017Recent results reported by Ciancio et al. have demonstrated the long term successful use of dual induction therapy in kidney transplant recipients. Our experience using...
Recent results reported by Ciancio et al. have demonstrated the long term successful use of dual induction therapy in kidney transplant recipients. Our experience using an "induction cocktail", thymoglobuline plus basiliximab, started in 2007 and we have treated 235 patients through the past 10years. In our population, we used a combination of CNIs and MMF or mTORi as maintenance therapy. Our results in term of patient and graft survival, acute rejection rate, renal function and incidence of post-transplant lymphoproliferative disorder support the data reported by Ciancio. We believe that double induction therapy allows on one hand to delay the CNIs introduction, reducing delayed graft function, and on the other hand protects the patient while building the targeted drugs exposures, so reducing the incidence of acute rejection.
Topics: Antibodies, Monoclonal; Antilymphocyte Serum; Basiliximab; Drug Therapy, Combination; Graft Rejection; Graft Survival; Humans; Induction Chemotherapy; Kidney Transplantation; Lymphoproliferative Disorders; Recombinant Fusion Proteins
PubMed: 28676335
DOI: 10.1016/j.trim.2017.06.005