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[Rinsho Ketsueki] the Japanese Journal... 2021Treatments of aplastic anemia comprise supportive therapy and aplastic anemia-specific therapy to recover from hematopoiesis. Supportive therapy includes transfusion,...
Treatments of aplastic anemia comprise supportive therapy and aplastic anemia-specific therapy to recover from hematopoiesis. Supportive therapy includes transfusion, granulocyte colony-stimulating factor, and iron chelation therapy in addition to symptomatic treatment. Aplastic anemia-specific treatments that aim to achieve hematopoietic recovery are immunosuppressive therapy, thrombopoietin receptor agonist (TPO-RA) treatment, allogeneic hematopoietic stem cell transplantation, and anabolic hormone therapy. Although the transplantation achieves complete recovery of hematopoiesis (healing), there is a risk of death from transplant-related complications. The most effective drug therapy is the combination of TPO-RA and the immunotherapy combined with anti-thymocyte globulin and cyclosporine. This treatment is also effective against secondary, drug-induced, or hepatitis-associated aplastic anemia. In the treatment of aplastic anemia, the treatment choice is made based on the disease severity and patient ages.
Topics: Anemia, Aplastic; Antilymphocyte Serum; Cyclosporine; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Transplantation; Humans
PubMed: 34497232
DOI: 10.11406/rinketsu.62.922 -
Frontiers in Immunology 2022Vascularized bone marrow (VBM) is essential in tolerance induction through chimerism. We hypothesized that the inclusion of VBM contributes to the induction of mystacial...
INTRODUCTION
Vascularized bone marrow (VBM) is essential in tolerance induction through chimerism. We hypothesized that the inclusion of VBM contributes to the induction of mystacial pad allotransplantation tolerance.
METHOD
In this study, 19 VBM, nine mystacial pad, and six sequential VBM and mystacial pad allografts were transplanted from Brown Norway (BN) rats to Lewis (LEW) rats to test our hypothesis. The VBM recipients were divided into antilymphocyte serum (ALS) monotherapy group (two doses of ALS on day 3 pretransplantation and day 1 posttransplantation), immunosuppressant group [a week of 2 mg/kg/day tacrolimus (Tac) and 3 weeks of 3 mg/kg/day rapamycin (RPM)], and combined therapy group. The mystacial pad recipients were divided into VBM and non-VBM transplantation groups, and both groups were treated with an immunosuppression regimen that consists of ALS, Tac, and RPM. For the recipients of sequential VBM and mystacial pad allotransplantations, additional Tac was given 1 week after mystacial pad transplantation. Allograft survival, donor-specific tolerance, and chimerism level were evaluated.
RESULTS
With the administration of ALS and short-term Tac and RPM treatments, VBM recipients demonstrated long-term graft survival (>120 days) with persistent chimerism for 30 days. CD3 T cells from tolerant rats showed donor-specific hyporesponsiveness and tolerance to donor skin grafts but not to third-party counterparts. Furthermore, mystacial pad graft recipients with VBM transplantation exhibited a higher allograft survival rate than those without VBM transplantation [median survival time (MST) >90 days vs. 70 days, < 0.05].
CONCLUSION
This study demonstrated that VBM transplantation is an efficient strategy to induce and maintain donor-specific tolerance for an osseous-free allograft.
Topics: Animals; Rats; Antilymphocyte Serum; Bone Marrow; Graft Rejection; Rats, Inbred BN; Rats, Inbred Lew; Sirolimus; Tacrolimus; Transplantation Tolerance
PubMed: 36578498
DOI: 10.3389/fimmu.2022.1059271 -
Expert Review of Hematology Oct 2019: About 60% of aplastic anemia (AA) patients are in need of further treatment after frontline standard immunosuppressive therapy (IST). This along with the prolonged... (Review)
Review
: About 60% of aplastic anemia (AA) patients are in need of further treatment after frontline standard immunosuppressive therapy (IST). This along with the prolonged survival of AA subjects who do not respond to or relapse after this treatment makes management of these patients a rising and very challenging issue. : Literature research, carried out from the most commonly used databases, included the following keywords: aplastic anemia, immunosuppressive treatment, antithymocyte globuline, ciclosporine A, refractory aplastic anemia, relapsing aplastic anemia, hematopoietic stem cell transplantation including haploidentical and cord blood transplantations thrombopoietin mimetics, supportive treatment, chelation and infections. Studies on the treatment of aplastic anemia with different levels of evidence were included. Top level of evidence studies (metanalyses and randomized prospective controlled trials) were a minority because severe AA, particularly in the subset of patients who fail upfront IST, is an extremely rare disease. Guidelines from National Societies and review articles were also included. : The most commonly used treatments after failure of upfront immunosuppression are hematopoietic stem cell transplantation, a second course of immunosuppression and thrombopoietin mimetics alone or in combination with immunosuppression. Other potential options are alemtuzumab, androgens, oral cyclosporine A in monotherapy. Not many comparative studies exist to clearly establish the superiority of one over another strategy. Therefore, the choice of the best treatment for these patients should rely on major driving factors like patient's age and comorbidities, availability of a matched unrelated donor, donor's characteristics and drug-availability.
Topics: Alemtuzumab; Androgens; Anemia, Aplastic; Antilymphocyte Serum; Clinical Trials as Topic; Cord Blood Stem Cell Transplantation; Cyclophosphamide; Cyclosporine; Disease Management; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Peptides; Practice Guidelines as Topic; Recurrence; Remission Induction; Survival Analysis; Unrelated Donors
PubMed: 31311355
DOI: 10.1080/17474086.2019.1645003 -
Clinical Nephrology Aug 2023Atypical hemolytic uremic syndrome (aHUS) is a genetic-based thrombotic microangiopathy (TMA) that is mediated by the activation of the alternative complement pathway....
PURPOSE
Atypical hemolytic uremic syndrome (aHUS) is a genetic-based thrombotic microangiopathy (TMA) that is mediated by the activation of the alternative complement pathway. Heterozygous deletion in CFHR3-CFHR1 occurs in 30% of the general population and has not been classically linked to aHUS. Post-transplant aHUS has been associated with a high rate of graft loss. Herein, we report our case series of patients who developed aHUS after solid-organ transplantation.
MATERIALS AND METHODS
Five consecutive cases of post-transplant aHUS were identified at our center. Genetic testing was performed in all but one.
RESULTS
One patient had a presumed TMA diagnosis before transplant. One heart and 4 kidney (KTx) transplant recipients were diagnosed with aHUS based on the clinical picture of TMA, acute kidney injury, and normal ADAMTS13 activity. Genetic mutation testing revealed heterozygous deletion in CFHR3-CFHR1 in 2 patients and a heterozygous complement factor I (CFI) variant of uncertain clinical significance (VUCS) (Ile416Leu) in a third. Four patients were on tacrolimus, 1 had anti-HLA-A68 donor-specific antibody (DSA), and another had borderline acute cellular rejection at the time of aHUS diagnosis. Four responded to eculizumab, and 1 out of 2 patients came off renal replacement therapy. One KTx recipient died from severe bowel necrosis in the setting of early post-transplant aHUS.
CONCLUSION
Calcineurin inhibitors, rejection, DSA, infections, surgery, and ischemia-reperfusion injury are common triggers that could unmask aHUS in solid-organ transplant recipients. Heterozygous deletion in CFHR3-CFHR1 and CFI VUCS may be important susceptibility factors acting as the first hit for alternative complement pathway dysregulation.
Topics: Humans; Atypical Hemolytic Uremic Syndrome; Mutation; Tacrolimus; Thrombotic Microangiopathies; Kidney Transplantation; Antilymphocyte Serum
PubMed: 37288831
DOI: 10.5414/CN111160 -
Transplantation Proceedings 2021This study aimed to compare the clinical outcomes of intestinal transplantation (ITX) between 2 groups by using medications for induction treatment and assess the...
BACKGROUND
This study aimed to compare the clinical outcomes of intestinal transplantation (ITX) between 2 groups by using medications for induction treatment and assess the utility of the current protocol.
METHODS
From 2003 to 2020, 11 patients underwent ITX. Recipients were classified into 2 groups: group IL-2Ra (interleukin-2 receptor antagonist therapy, n = 6) and ATG (rabbit antithymocyte globulin therapy, n = 5). We conducted a retrospective review of patient and graft survival rates and the postoperative course.
RESULTS
The 1-, 5-, and 10-year patient and graft survival rates of the 11 primary grafts in the 11 recipients were 100%, 88.9%, 62.2% and 90.0%, 78.8%, 56.3%, respectively. The median duration of follow-up for the IL-2Ra and ATG groups was 197.3 and 87.3 months, respectively. The 1-, 5-, and 10-year patient survival rates were 100%, 83.3%, 50% and 100%, 100%, 100% for the IL-2Ra and ATG groups, respectively (P = .25) and 83.3%, 66.7%, 33.3% and 100%, 100%, 100% for graft survival in the IL-2Ra and ATG groups, respectively (P = .08). The incidence of moderate and severe acute rejection was 100% and 20% in the IL-2Ra and ATG groups, respectively (P = .02). The 1- and 5-year moderate and severe rejection-free survival rates were 33.3%, 0% and 80%, 80% in the IL-2Ra and ATG groups, respectively (P = .04).
CONCLUSIONS
ATG significantly suppressed moderate and severe acute rejection compared with IL-2Ra, thereby showing better short- and mid-term rejection-free survival rates. Additional clinical experience is needed to determine the optimal regimen for the management of ITX recipients.
Topics: Antilymphocyte Serum; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Intestines; Japan; Kidney Transplantation; Receptors, Interleukin-2; Retrospective Studies
PubMed: 34266655
DOI: 10.1016/j.transproceed.2021.06.021 -
Transplantation Oct 2020
Topics: Antilymphocyte Serum; Immunosuppression Therapy; Intestines; Rituximab
PubMed: 31978039
DOI: 10.1097/TP.0000000000003081 -
International Journal of Hematology Mar 2024The treatment of aplastic anemia (AA) has significantly advanced in the last 50 years, evolving from a fatal condition to one where survival rates now exceed 80-85%.... (Review)
Review
The treatment of aplastic anemia (AA) has significantly advanced in the last 50 years, evolving from a fatal condition to one where survival rates now exceed 80-85%. Hematopoietic stem cell transplantation (HSCT) and immunosuppressive therapy (IST) have become the primary treatments, with the latter widely adopted due to factors like the scarcity of compatible donors, patient age, comorbidities, and limited HSCT access. A therapy breakthrough was the introduction of antithymocyte globulin (ATG), with its effectiveness further boosted by cyclosporine. However, it took years to achieve another major milestone in management. Initially, treatments aimed to intensify immunosuppression following the success of the ATG-cyclosporine combination, but these methods fell short of expectations. A major turning point was combining immunosuppression with stem cell stimulation, surpassing the efficacy of IST alone. Earlier, growth factors had shown limited success in AA treatment, but thrombopoietin receptor agonists represented a significant advancement. Initially applied alone as salvage, these were later combined with IST, forming the most effective current regimen for medically managing SAA. Horse ATG is the preferred formulation combined with cyclosporine and eltrombopag. This progress in AA treatment offers improved outcomes for patients afflicted with this once-lethal disease.
Topics: Humans; Immunosuppressive Agents; Anemia, Aplastic; Cyclosporine; Antilymphocyte Serum; Immunosuppression Therapy; Treatment Outcome
PubMed: 38403842
DOI: 10.1007/s12185-024-03713-3 -
Clinical Transplantation Nov 2022We provide a contemporary consideration of long-term outcomes and trends of induction therapy use following lung transplantation in the United States. (Review)
Review
OBJECTIVES
We provide a contemporary consideration of long-term outcomes and trends of induction therapy use following lung transplantation in the United States.
METHODS
We reviewed the United Network for Organ Sharing registry from 2006 to 2018 for first-time, adult, lung-only transplant recipients. Long-term survival was compared between induction classes (Interleukin-2 inhibitors, monoclonal or polyclonal cell-depleting agents, and no induction therapy). A 1:1 propensity score match was performed, pairing patients who received basiliximab with similar risk recipients who did not receive induction therapy. Outcomes in matched populations were compared using Cox, Kaplan-Meier and Logistic regression modeling.
MEASUREMENTS AND MAIN RESULTS
22 025 recipients were identified; 8003 (36.34%) were treated with no induction therapy, 11 045 (50.15%) with basiliximab, 1556 (7.06%) with alemtuzumab and 1421 (6.45%) with anti-thymocyte globulin. Compared with those who received no induction, patients receiving basiliximab, alemtuzumab or anti-thymocyte globulin were found on multivariable Cox-regression analyses to have lower long-term mortality (all p < .05). Following propensity score matching of basiliximab and no induction populations, analyses demonstrated a statistically significant association between basiliximab use and long- term survival (p < .001). Basiliximab was also associated with a lower risk of acute rejection (p < .001) and renal failure (p = .002).
CONCLUSION
Induction therapy for lung transplant recipients-specifically basiliximab-is associated with improved long-term survival and a lower risk of renal failure or acute rejection.
Topics: Adult; Humans; Antilymphocyte Serum; Immunosuppressive Agents; Graft Rejection; Antibodies, Monoclonal; Basiliximab; Lung Transplantation; Alemtuzumab; Renal Insufficiency; Recombinant Fusion Proteins
PubMed: 35848518
DOI: 10.1111/ctr.14782 -
Blood Reviews Nov 2023Haploidentical donor stem cell transplantation (haplo-SCT) has made great advances in recent decades. The granulocyte colony-stimulating factor (G-CSF)- and... (Review)
Review
Haploidentical donor stem cell transplantation (haplo-SCT) has made great advances in recent decades. The granulocyte colony-stimulating factor (G-CSF)- and antithymocyte globulin (ATG)-based protocol, which is known as the Beijing Protocol, represents one of the current T-cell repletion strategies in haplo-SCT. The key elements of the Beijing Protocol for graft versus host disease (GvHD) prophylaxis include G-CSF inducing T-cell tolerance and altering graft cell components, as well as ATG administration exerting an immunoregulatory effect for intensive prophylaxis. This review will summarize the GvHD incidence, the underlying novel mechanism for GvHD prophylaxis, how to optimize GvHD prophylaxis, and the recent advances of the Beijing Protocol, mainly focusing on the issues of GvHD.
Topics: Humans; Antilymphocyte Serum; Transplantation, Haploidentical; Hematopoietic Stem Cell Transplantation; Graft vs Host Disease; China; Granulocyte Colony-Stimulating Factor; Transplantation Conditioning
PubMed: 36404244
DOI: 10.1016/j.blre.2022.101035 -
Bone Marrow Transplantation Apr 2022The majority of contemporary allogeneic hematopoietic stem cell transplantation (HCT) procedures utilize partially HLA-mismatched stem cell grafts. Donor-specific... (Review)
Review
The majority of contemporary allogeneic hematopoietic stem cell transplantation (HCT) procedures utilize partially HLA-mismatched stem cell grafts. Donor-specific anti-HLA antibodies (DSA) are associated with primary graft failure independent of the graft source, conditioning intensity and other patient and donor factors. Here we provide an update on testing and monitoring of DSA, review the impact of DSA on stem cell engraftment, and present promising desensitization modalities. Ultimately, we attempt to provide practical recommendations for DSA screening and mitigation strategies.
Topics: Antibodies; Antilymphocyte Serum; HLA Antigens; Hematopoietic Stem Cell Transplantation; Humans; Stem Cell Transplantation; Tissue Donors
PubMed: 35082370
DOI: 10.1038/s41409-022-01578-w