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Cells Oct 2021Idiopathic acquired aplastic anemia can be successfully treated with Anti Thymocyte Globulin (ATG)-based immune suppressive therapy and is therefore considered a T... (Review)
Review
Idiopathic acquired aplastic anemia can be successfully treated with Anti Thymocyte Globulin (ATG)-based immune suppressive therapy and is therefore considered a T cell-mediated auto immune disease. Based on this finding, several other forms of idiopathic acquired bone marrow failure are treated with ATG as well. For this review, we extensively searched the present literature for evidence that ATG can lead to enduring remissions in different forms of acquired multi- or single-lineage bone marrow failure. We conclude that ATG-based therapy can lead to an enduring hematopoietic response and increased overall survival (OS) in patients with acquired aplastic aplasia. In patients with hypocellular myelodysplastic syndrome, ATG can lead to a hematological improvement without changing the OS. ATG seems less effective in acquired single-lineage failure diseases like Pure Red Cell Aplasia, Amegakaryocytic Thrombocytopenia and Pure White Cell Aplasia, suggesting a different pathogenesis in these bone marrow failure states compared to aplastic anemia. T cell depletion is hypothesized to play an important role in the beneficial effect of ATG but, as ATG is a mixture of polyclonal antibodies binding to different antigens, other anti-inflammatory or immunomodulatory effects could play a role as well.
Topics: Adult; Antilymphocyte Serum; Bone Marrow; Bone Marrow Failure Disorders; Humans; Prospective Studies
PubMed: 34831130
DOI: 10.3390/cells10112905 -
Experimental and Clinical... Apr 2021The number of elderly kidney transplant recipients is increasing, and age-tailored induction immunosuppression regimens are needed. We compared safety and efficacy of...
OBJECTIVES
The number of elderly kidney transplant recipients is increasing, and age-tailored induction immunosuppression regimens are needed. We compared safety and efficacy of basiliximab versus thymoglobulin at various dosages.
MATERIALS AND METHODS
Of 590 kidney transplants at our center from 2012 to 2019, 119 (20.1%) were for recipients over 65 years of age; 118 patients received deceased donor kidneys, and 1 received a related living donor kidney. We retrospectively reviewed medical records for demographics, baseline characteristics, donor characteristics, induction regimens, infectious complications, graft function, and patient survival.
RESULTS
Patients were subdivided into the following 4 induction immunosuppression groups: basiliximab (n = 15, 12.6%), 3 mg/kg thymoglobulin (n = 8, 6.7%), 4.5 mg/kg thymoglobulin (n = 67, 56.3%), and 6 mg/kg thymoglobulin (n = 29, 24.4%). All patients received pulse doses of methylprednisolone followed by a prednisone taper. Other maintenance immunosuppression agents included tacrolimus and mycophenolic acid. Recipients in the basiliximab and 3 mg/kg thymoglobulin groups were older (median age ⟩70 years; P ⟨ .001). The 4.5 and 6 mg/kg thymoglobulin groups had higher proportions of African American patients and patients with calculated panel reactive antibody over 20%. There were significantly fewer infectious complications in the basiliximab and 3 mg/kg thymoglobulin groups. Despite differences in biopsy-proven acute rejection rates, estimated glomerular filtration rate and graft and patient survival rates at 1 year were similar across groups. All patients with biopsy-proven acute rejection were African American patients.
CONCLUSIONS
Kidney transplant in patients ≥65 years is safe and feasible. Changes in this unique population's immune system warrant age-tailored regimens. We found that patients at low immunologic risk would benefit from basiliximab orthymoglobulin at 3 mg/kg. Regardless of calculated panel reactive antibodies, African American patients should be considered as high immunologic risk group forrejection, and higher thymoglobulin dosing should be considered.
Topics: Aged; Aged, 80 and over; Antilymphocyte Serum; Basiliximab; Humans; Immunosuppression Therapy; Kidney Transplantation; Retrospective Studies; Treatment Outcome
PubMed: 33834956
DOI: 10.6002/ect.2020.0434 -
Cancers May 2023Graft-versus-host disease (GVHD) is one of the most important complications of allogeneic hematopoietic stem cell transplantation. Rabbit antilymphocyte serum (ATG/ATLG)...
Graft-Versus-Host Disease Prophylaxis with Antithymocyte Globulin in Patients Receiving Stem Cell Transplantation from Unrelated Donors: An Observational Retrospective Single-Center Study.
Graft-versus-host disease (GVHD) is one of the most important complications of allogeneic hematopoietic stem cell transplantation. Rabbit antilymphocyte serum (ATG/ATLG) is recommended for GVHD prophylaxis, while its appropriate dosing is debated. We performed a retrospective single-center study to examine the outcome of patients receiving ATG at the dose of 5 mg/kg as GVHD prophylaxis for unrelated donor (URD) HSCT. We collected data from all consecutive adult patients with hematological malignancies who had undergone allogeneic HSCT from URDs at the Stem Cell Transplant Center of the Città della Salute e della Scienza Hospital of Torino between July 2008 and July 2021. The primary aim was to ascertain the cumulative incidence (CI) for acute GVHD (aGVHD) and chronic GVHD (cGVHD); the secondary aim was to ascertain the CI for NRM (Non-Relapse Mortality) and RI (Relapse Incidence), as well the overall survival (OS) and infection incidence within 30 days of transplantation. We included in the analysis 226 patients who collectively underwent 231 HSCTs. The CI of grade II-IV aGVHD was found to be 29.9%, while that of moderate to severe cGVHD was 29.8%. The CI of NRM recorded at 1, 2, and 3 years after transplant was 18.2%, 19.6%, and 20.2%, respectively. The CI of RI at 1, 2, and 3 years from transplant was recorded to be 17.8%, 21.0%, and 21.6%, respectively. The median follow-up was 56 months, while the median OS for the whole cohort was not established; the OS at 1, 3, and 5 years from transplant was 69.6%, 59.3%, and 57.2%, respectively. We registered 88 bacteremias in 82/231 patients (35.5%), while invasive fungal infections occurred in 12/231 patients (5.2%). Our study suggests that the use of ATG at 5 mg/kg is highly effective in limiting the occurrence of both aGVHD and cGVHD, ensuring a low NRM, RI, and infection incidence.
PubMed: 37345098
DOI: 10.3390/cancers15102761 -
Experimental and Clinical... Aug 2022Our study was conducted to determine the effects of intraoperative antithymocyte globulin administration on donor hearts procured after cardiocirculatory death. We... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
Our study was conducted to determine the effects of intraoperative antithymocyte globulin administration on donor hearts procured after cardiocirculatory death. We evaluated the impact of antithymocyte globulin on graft function and related parameters during isothermic blood cardioplegia.
MATERIALS AND METHODS
In this prospective and randomized single center study, 30 patients with orthotropic heart transplant were divided into 2 groups: group 1 included 15 patients who received retrograde antithymocyte globulin infusion via coronary sinus intraoperatively and immediately after organ procurement and group 2 included 15 patients who received traditional antithymocyte globulin infusion after implantation.
RESULTS
Study patients had a mean age of 33.8 years (range, 15-56 y). All patients had panel reactive antibody less than 10% except for 3 patients. The cluster of differentiation 3-positive cell count decrease was more than 20%. The inotropic therapy dose required and the myocardial pressure (stiffness) were less for group 1 patients. These patients had less acute rejection episodes than group 2 (0% vs 13.3%; P < .05).
CONCLUSIONS
Favorable clinical outcomes were observed in terms of less acute rejection episodes and better graft function at least during the early posttransplant period. Intraoperative antithymocyte globulin treatment may have a preventive effect for acute cellular rejection in heart transplant patients.
Topics: Adult; Antilymphocyte Serum; Graft Rejection; Graft Survival; Heart Transplantation; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Transplantation; Prospective Studies; Tissue Donors; Treatment Outcome
PubMed: 30251943
DOI: 10.6002/ect.2017.0230 -
Frontiers in Endocrinology 2023Post-transplant diabetes mellitus (PTDM) is a common complication among cardiac transplant recipients, causing diabetes-related complications and death. While certain...
INTRODUCTION
Post-transplant diabetes mellitus (PTDM) is a common complication among cardiac transplant recipients, causing diabetes-related complications and death. While certain maintenance immunosuppressive drugs increase PTDM risk, it is unclear whether induction immunosuppression can do the same. Therefore, we evaluated whether induction immunosuppression with IL-2 receptor antagonists, polyclonal anti-lymphocyte antibodies, or Alemtuzumab given in the peri-transplant period is associated with PTDM.
METHODS
We used the Scientific Registry of Transplant Recipients database to conduct a cohort study of US adults who received cardiac transplants between January 2008-December 2018. We excluded patients with prior or multiple organ transplants and those with a history of diabetes, resulting in 17,142 recipients. We created propensity-matched cohorts (n=7,412) using predictors of induction immunosuppression and examined the association between post-transplant diabetes and induction immunosuppression by estimating hazard ratios using Cox proportional-hazards models.
RESULTS
In the propensity-matched cohort, the average age was 52.5 (SD=13.2) years, 28.7% were female and 3,706 received induction immunosuppression. There were 867 incident cases of PTDM during 26,710 person-years of follow-up (32.5 cases/1,000 person-years). There was no association between induction immunosuppression and post-transplant diabetes (Hazard Ratio= 1.04, 95% confidence interval 0.91 - 1.19). Similarly, no associations were observed for each class of induction immunosuppression agents and post-transplant diabetes.
CONCLUSION
The use of contemporary induction immunosuppression in cardiac transplant patients was not associated with post-transplant diabetes.
Topics: Adult; Humans; Female; Middle Aged; Male; Cohort Studies; Immunosuppressive Agents; Immunosuppression Therapy; Antilymphocyte Serum; Diabetes Mellitus
PubMed: 37929038
DOI: 10.3389/fendo.2023.1248940 -
Journal of the American Society of... Nov 2019
Topics: Antilymphocyte Serum; Histocompatibility Testing; Humans; Kidney Transplantation; Kinetics; Waiting Lists
PubMed: 31653785
DOI: 10.1681/ASN.2019090946 -
Frontiers in Immunology 2022In sensitized deceased donor kidney allograft recipients, the most frequent induction therapy is anti-thymocyte globulins (ATG), including Thymoglobulin® (Thymo) and... (Observational Study)
Observational Study
INTRODUCTION
In sensitized deceased donor kidney allograft recipients, the most frequent induction therapy is anti-thymocyte globulins (ATG), including Thymoglobulin® (Thymo) and ATG-Fresenius (ATG-F).
METHODS
We conducted a 3-year monocentric observational study to compare the impact of ATGs on hematological parameters. We included adult kidney transplant recipients treated with ATG induction therapy, either Thymo or ATG-F, on a one-in-two basis. The primary endpoint was red blood cell (RBC) transfusions within 14 days after transplantation.
RESULTS
Among 309 kidney allograft recipients, 177 (57.2%) received ATG induction, 90 (50.8 %) ATG-F, and 87 (49.2%) Thymo. The ATG-F group received significantly more RBC transfusions (63.3% vs. 46% p = 0.02) and in bigger volumes (p = 0.01). Platelet transfusion was similar in both groups. Within 14 and 30 days after transplantation, older age, ATG-F induction, and early surgical complication were independently associated with RBC transfusion. Patient survival rate was 95%, and the death-censored kidney allograft survival rate was 91.5% at 12 months post-transplantation. There was no difference in the incidence of acute rejection and infections or in the prevalence of anti-HLA donor-specific antibodies.
DISCUSSION
In conclusion, after kidney transplantation, ATG-F is an independent risk factor for early RBC transfusion and early thrombocytopenia without clinical and biological consequences. These new data should be clinically considered, and alternatives to ATG should be further explored.
Topics: Adult; Humans; Antilymphocyte Serum; Kidney Transplantation; Graft Rejection; Graft Survival; Erythrocyte Transfusion; Immunosuppressive Agents
PubMed: 36532030
DOI: 10.3389/fimmu.2022.1045580 -
Clinical Lymphoma, Myeloma & Leukemia Sep 2021Anti-thymocyte globulin (ATG) is commonly used to prevent graft-versus-host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). To...
Addition of Anti-thymocyte Globulin in Allogeneic Stem Cell Transplantation With Peripheral Stem Cells From Matched Unrelated Donors Improves Graft-Versus-Host Disease and Relapse Free Survival.
Anti-thymocyte globulin (ATG) is commonly used to prevent graft-versus-host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). To evaluate the impact of ATG as part of the GvHD prophylaxis in our institution, we report the outcome of 415 patients with matched unrelated donors (MUD) transplanted for hematological malignancies with or without ATG from 2005 to 2019 at Oslo University Hospital, Norway. The following groups were compared: (1) 154 patients transplanted with peripheral blood stem cells (PBSC) without ATG 2005-2014. (2) 137 patients transplanted with bone marrow stem cells (BMSC) 2005-2019. (3) 124 patients transplanted with PBSC and ATG (PBSC + ATG) 2014-2019. Three years survival was similar in the groups, 61% following allografting with PBSC, 54% with BMSC, and 59% with PBSC + ATG. Acute GvHD grade III-IV was 14%, 14%, and 7%; chronic GvHD was 81%, 32, and 26%; and extensive cGvHD 44%, 15%, and 6% in the corresponding groups. Both acute and chronic GvHD were significantly reduced in the PBSC + ATG-versus the PBSC group (p < 0.05 and p < 0.001 respectively).Transplant-related mortality (TRM) was 33%, 25%, and 17% (p = 0.18). Graft versus host disease and relapse free survival (GRFS) at 3 years was 43 %, 43%, and 64% in the groups. Adding ATG to the GvHD prophylaxis regimen of MUD allo-HSCT with PBSC resulted in a substantial reduction of both acute and chronic GvHD without compromising the disease control, reflected in a superior 3 years GRFS.
Topics: Adult; Antilymphocyte Serum; Disease-Free Survival; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Peripheral Blood Stem Cells; Retrospective Studies; Transplantation Conditioning; Transplantation, Homologous; Unrelated Donors
PubMed: 34158268
DOI: 10.1016/j.clml.2021.05.003 -
Nefrologia 2023Post transplant lymphoproliferative disorders (PTLD) are heterogeneous lymphoid proliferations in recipients of solid organs which seem to be related to Epstein Barr... (Observational Study)
Observational Study
INTRODUCTION
Post transplant lymphoproliferative disorders (PTLD) are heterogeneous lymphoid proliferations in recipients of solid organs which seem to be related to Epstein Barr Virus (EBV). The use of antilymphocyte antibodies, EBV seronegativity in the recipient,acute rejection and CMV infection have been identified as classical risk factors.
MATERIAL Y METHODS
We have studied in a retrospective observational study, the incidence of PTLD in a period of 22 years, its relationship with EBV, presence of classical risk factors and outcome in 21546 simple adult renal transplant recipients from cadaveric and living donors, transplanted in 21 hospitals from 1990 to 2009.
RESULTS
A total of 275 recipients developed PTLD (1,2%),195 males (70,9%), 80 females (29,1%) aged 59.2 (p25 44.7 p75 68)years. Two hundred forty-five (89.0%) were 1st transplant recipients and 269 (97,8%) from cadaveric donors. EBV in the tissue was reported in 94 out of the 155 studied recipients (60.6%) and 86.0% of the proliferations were due to B lymphocytes. PTLD median appearance after transplant were 42.months (p25, 75, 12, 77, 5). One hundred eighty-eight recipients out of 275 patients (68.3%) had any classical risk factor and the use of antilymphocyte antibodies was the most frequent. During the follow-up, 172 patients died (62,5%) and 103 (37,5%) had a complete remission. The main cause of death was PTLD progression (n = 91, 52,9%), followed by sepsis (n = 24, 13,9%). The follow-up period post-transplant of the recipients was between 3 and 22 years. The incidence was 0,14% during the first year post-trasplant and 0.98% the cumulative incidence at 10 years. Patient survival after diagnosis was 51%, 44% and 39% after 1, 2 and 5 years, respectively. Finally, overall graft survival was 48%, 39% and 33% at the same periods.
CONCLUSION
PTLD has a low incidence in renal transplant recipients. Most of the proliferations are due to B lymphocytes and seem to have a close relationship with EBV. PTLD can develop in the absence of classical risk factors. The prognosis is poor, mainly due to PTLD progression, but the survivors can even maintain their grafts.
Topics: Male; Adult; Female; Humans; Kidney Transplantation; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Antilymphocyte Serum; Longitudinal Studies; Lymphoproliferative Disorders; Cadaver
PubMed: 37813738
DOI: 10.1016/j.nefroe.2023.09.001 -
British Journal of Haematology Feb 2021Acquired severe aplastic anaemia (SAA) has an immune pathogenesis, and immunosuppressive therapy (IST) with anti-thymocyte globulin and cyclosporine is effective...
Acquired severe aplastic anaemia (SAA) has an immune pathogenesis, and immunosuppressive therapy (IST) with anti-thymocyte globulin and cyclosporine is effective therapy. Eltrombopag (EPAG) added to standard IST was associated with higher overall and complete response rates in patients with treatment-naïve SAA compared to a historical IST cohort. We performed a paediatric subgroup analysis of this trial including all patients aged <18 years who received EPAG plus standard IST (n = 40 patients) compared to a historical cohort (n = 87) who received IST alone. Response, relapse, clonal evolution, event-free survival (EFS), and overall survival were assessed. There was no significant difference in either the overall response rate (ORR) or complete response rate at 6 months (ORR 70% in EPAG group, 72% in historical group, P = 0·78). Adults (≥18 years) had a significantly improved ORR of 82% with EPAG compared to 58% historically (P < 0·001). Younger children had lower response rates than did adolescents. The trend towards relapse was higher and EFS significantly lower in children who received EPAG compared to IST alone. Addition of EPAG added to standard IST did not improve outcomes in children with treatment-naïve SAA. EPAG in the paediatric population should not automatically be considered standard of care. Registration: clinicaltrials.gov (NCT01623167).
Topics: Adolescent; Anemia, Aplastic; Antilymphocyte Serum; Benzoates; Child; Cyclosporine; Female; Humans; Hydrazines; Immunosuppressive Agents; Male; Pyrazoles; Treatment Outcome
PubMed: 33410523
DOI: 10.1111/bjh.17232