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Transplant International : Official... 2022Delayed graft function (DGF) is a common complication of kidney transplantation and frequently leads to the necessity of surveillance biopsies. The purpose of this study...
Delayed graft function (DGF) is a common complication of kidney transplantation and frequently leads to the necessity of surveillance biopsies. The purpose of this study is to describe the histological findings in surveillance biopsies of deceased donor kidney transplant recipients and evaluate the risk factors for graft outcomes. This is a monocentric, retrospective study including kidney transplant recipients that underwent a graft biopsy during the DGF period between January 2006 and July 2019. 356 biopsies were performed in 335 deceased donor transplant recipients. Biopsies were analyzed according to the Banff classification. The main histological findings were: acute tubular necrosis in 150 biopsies (42.1%), acute rejection in 96 biopsies (26.9%), and borderline findings in 91 biopsies (25.5%). In the multivariate analysis, recipient age ( = 0.028) and DGF duration ( = 0.005) were associated with rejection, antibody-induction with anti-thymocyte globulin (ATG) was protective ( = 0.001). The occurrence of rejection was associated with lower death-censored graft survival (log-rank; = 0.009). Surveillance biopsies of kidney grafts experiencing DGF remain an essential tool for the care of kidney transplant recipients. The recipient's age and duration of DGF are independent risk factors for acute rejection, while antibody-induction therapy with ATG is associated with protection from its occurrence.
Topics: Antibodies; Antilymphocyte Serum; Biopsy; Delayed Graft Function; Graft Rejection; Graft Survival; Humans; Kidney Transplantation; Retrospective Studies; Risk Factors
PubMed: 35401043
DOI: 10.3389/ti.2022.10344 -
American Journal of Hematology Jun 2023Immune severe aplastic anemia (SAA) is characterized by pancytopenia and immune-mediated bone marrow destruction. SAA may be treated with hematopoietic stem cell...
Immune severe aplastic anemia (SAA) is characterized by pancytopenia and immune-mediated bone marrow destruction. SAA may be treated with hematopoietic stem cell transplantation (HSCT) or immunosuppressive therapy (IST). However, 30% of patients treated with IST relapse. We previously reported a clinical trial of alemtuzumab in which more than half of 25 relapsed SAA patients (56%) responded hematologically. Here, we present long-term results of a total of 42 patients. Participants with SAA who had previously completed antithymocyte globulin (ATG)-based IST, but had relapsed, were enrolled on this study. Alemtuzumab was administered intravenously (IV) (n = 28) or subcutaneously (SC) (n = 14). The primary endpoint was hematologic response at 6 months. Secondary endpoints included relapse, clonal evolution, and survival. This trial was registered at clinicaltrials.gov (NCT00195624). Patients were enrolled over 9 years, with median follow-up of 6 years. Median age was 32 years, with 57% being female. At 6 months, 18 patients (43%) achieved response; 15 (54%) of those who received IV compared with 3 (21%) who received SC therapy. Six patients (14%) had durable long-term response without need for subsequent AA-directed therapy or HSCT at last follow-up. Nine patients had clonal evolution, with high-risk evolution occurring in 6. Overall survival was 67% at median follow-up of 6 years. Prolonged iatrogenic immunosuppression was observed as long as 2 years after alemtuzumab administration. Alemtuzumab induces responses in relapsed SAA, some of which are durable long-term. However, immunosuppression can persist for years, requiring long-term monitoring.
Topics: Humans; Female; Adult; Male; Immunosuppressive Agents; Cyclosporine; Alemtuzumab; Anemia, Aplastic; Treatment Outcome; Antilymphocyte Serum; Recurrence
PubMed: 37021397
DOI: 10.1002/ajh.26924 -
Annals of Palliative Medicine May 2021When it comes to the treatment of aplastic anemia fever, the Guidelines for Aplastic Anemia regards Anti-thymocyte globulin (ATG) combined with eltrombopag as the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
When it comes to the treatment of aplastic anemia fever, the Guidelines for Aplastic Anemia regards Anti-thymocyte globulin (ATG) combined with eltrombopag as the standard immunosuppressive treatment plan, and ATG is the main mode to treat severe aplastic anemia. A large number of prospective studies and clinical trials have confirmed the clinical application value of eltrombopag in aplastic anemia. Although ATG combined with eltrombopag brings satisfactory treatment results, the safety of long-term use is still unclear. Therefore, more clinical trial studies are needed to verify its safety.
METHODS
Literature in the Chinese and English medical databases was searched using the following search terms: "Antithymocyte globulin", "severed aplastic anemia" and "eltrombopag". Patients in the experimental group were administered ATG combined with eltrombopag and patients in the control group received ATG treatment alone. Rev Man5.3 software was used for meta-analysis.
RESULTS
A total of 16 references were included in this meta-analysis. Heterogeneity tests examining total effective rate demonstrated that Chi2 =4.48, df =15, I2=0%<50%, and P=1.00>0.01. The effective rate of the experimental group was higher than that of the control group, with odds ratio (OR) =1.90 and 95% confidence interval (CI) 1.35 to 2.68 (Z=3.70, P=0.0002). The heterogeneity test results of the survival rate within 2 years were Chi2 =3.09, df =7, I2=0%<50%, and P=0.88>0.01. The survival rate of the experimental group was higher than that of the control group, with OR =2.54, and 95% CI: 1.58 to 4.09 (Z=3.84, P=0.0001). The heterogeneity test results of the mortality rate were Chi2 =3.49, df =6, I2=0%<50%, and P=0.75>0.01. The mortality rate of the experimental group was lower than that of the control group, with OR =0.48 and 95% CI: 0.33 to 0.70 (Z=3.84, P=0.0001). The heterogeneity test results of the occurrence of side effects were Chi2 =0.12, df =3, I2=0%<50%, P=0.99>0.01. The incidence of side effects in the experimental group was lower than that in the control group, with OR =0.74, 95% CI: 0.48 to 1.17 (Z=1.29, P=0.20).
DISCUSSION
This meta-analysis demonstrated that the combination of ATG with eltrombopag in the treatment of SAA is safer and more effective than ATG alone.
Topics: Anemia, Aplastic; Antilymphocyte Serum; Benzoates; Humans; Hydrazines; Prospective Studies; Pyrazoles; Treatment Outcome
PubMed: 34107711
DOI: 10.21037/apm-21-1049 -
Transplantation and Cellular Therapy May 2021Haploidentical hematopoietic cell transplantation (HaploHCT) is an alternative treatment option for patients without a suitable 10/10 HLA matched donor. We share an...
Experience Using Anti-Thymocyte Globulin With Post-Transplantation Cyclophosphamide for Graft-Versus-Host Disease Prophylaxis in Peripheral Blood Haploidentical Stem Cell Transplantation.
Haploidentical hematopoietic cell transplantation (HaploHCT) is an alternative treatment option for patients without a suitable 10/10 HLA matched donor. We share an updated experience at our center of using in vivo dual T-cell depletion with anti-thymocyte globulin (ATG) and post-transplantation cyclophosphamide (PTCy) in peripheral blood haploHCT and report the impact of reducing the dose of ATG from 4.5 mg/kg to 2 mg/kg on post-transplantation complications and outcomes. Ninety-five consecutive adults underwent haploHCT at our center between August 2016 and February 2020, all of whom were included in the study. Nine (9.5%) patients received myeloablative conditioning, and 86 (90.5%) patients underwent reduced-intensity haploHCT. All patients received thymoglobulin, PTCy and cyclosporine (CsA) for graft-versus-host disease (GVHD) prophylaxis: Sixty (63.2%) patients received 4.5 mg/kg, and 35 (36.8%) patients received 2 mg/kg of ATG. Clinical information was collected retrospectively and updated in June 2020. The median age was 57 (18-73), and acute myeloid leukemia was the most prevalent diagnosis (58.9%). The day 100 cumulative incidence of grade II-IV and grade III-IV aGVHD, and 1-year moderate/severe cGVHD were 22.3%, 11.1%, and 20.2%, respectively. Those patients who received 2 mg/kg of ATG had higher incidence of grade III-IV aGVHD (23.9% vs 3.5%, P = .006) and comparable moderate/severe cGVHD (1-year 20.6% vs 19.8%, P = .824) than those patients who received 4.5 mg/kg. Overall, the 18-month overall survival (OS), relapse-free survival (RFS), and non-relapse mortality (NRM) were 43.8%, 38.4%, and 40.2%, respectively. The reduction of the ATG dose did not have a significant impact in OS (hazard ratio [HR] 1.06, P = .847), RFS (HR 0.984, P = .955), and in NRM (HR 1.38; P = .348). The reduction of the ATG resulted in a negative impact on aGVHD without conferring any benefit in OS, RFS, and NRM. Consequently, the ATG dose used at our institution in combination with PTCy and CsA for haploHCT continues to be 4.5 mg/kg.
Topics: Adult; Antilymphocyte Serum; Cyclophosphamide; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Middle Aged; Retrospective Studies
PubMed: 33965185
DOI: 10.1016/j.jtct.2021.02.007 -
Annals of Palliative Medicine Nov 2021Teniposide, as a more potent inhibitor of topoisomerase II compared with etoposide, shows less damage on hematopoietic stem cells. Few data are available on teniposide...
Teniposide-intensified hematopoietic stem cell transplantation with acute graft versus host disease prophylaxis with anti-thymocyte globulin provides good results in high-risk or refractory recurrent hematopoietic malignant diseases.
BACKGROUND
Teniposide, as a more potent inhibitor of topoisomerase II compared with etoposide, shows less damage on hematopoietic stem cells. Few data are available on teniposide in hematopoietic stem cell transplantation (HSCT) for high-risk or refractory recurrent hematopoietic malignant diseases, particularly for acute myeloid leukemia (AML).
METHODS
A retrospective single arm study was conducted to confirm the feasibility of teniposide (300 mg/m2) -intensified HSCT in the treatment of high-risk or refractory recurrent hematopoietic malignant disease by analysing the outcomes of 32 patients, who received transplantation between January 2016 and December 2018. Univariate and multivariate analyses were performed to evaluate prognostic factors of the endpoints. Statistically significant factors (P<0.05) in multivariate analyses were regarded to be predictive.
RESULTS
All patients achieved myeloid engraftment at a median of 13 days (range, 9-28 days), platelet engraftment at 15.5 days (range, 6-142 days), with a cumulative incidence (CI) of platelet engraftment of 93.75%±0.26%. The CI of grade II-IV acute graft versus host disease (aGVHD) was 43.75%±0.80% and that of grade III-IV aGVHD 12.50%±0.35%. The CI of chronic (c)GVHD was 74.07%±0.82% and that of extensive cGVHD 33.33%±0.87%. The CI of relapse was 35.03%±0.76%. The one-year probability of overall survival (OS) was 62.50%±0.09%, while 2-year OS was 46.90%±0.09%, and those of 1- and 2-year leukemia-free-survival (LFS) were 56.30%±0.09% and 46.90%±0.09%, respectively. Generally, the OS and LFS until the end of our follow up were 43.50%±0.09% and 34.80%±0.11%, respectively. The probability of GVHD-free and relapse-free survival (GRFS) was 24.60%±0.08%. Multivariate analysis indicated that the probability of OS was significantly lower in patients with a disease duration of more than 280 days before receiving HSCT and in those with fewer mononuclear cells. For LFS, other than the above two factors, failure to achieve complete response (CR) before HSCT was another independent risk factor. Similarly, the probability of GRFS was significantly lower in patients with longer disease duration (≥280 days) and those receiving stem cells from female donors.
CONCLUSIONS
For patients with high-risk or refractory recurrent hematopoietic malignant disease, teniposide-based conditioning regimens followed by allo-HSCT can be considered as an alternative therapy with encouraging prognoses.
Topics: Antilymphocyte Serum; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Recurrence; Retrospective Studies; Teniposide
PubMed: 34872304
DOI: 10.21037/apm-21-3122 -
Bone Marrow Transplantation Nov 2021Nonmyeloablative regimens are used for allogeneic hematopoietic cell transplantation (HCT) of older or medically unfit patients, but successful outcome is still hindered...
Nonmyeloablative regimens are used for allogeneic hematopoietic cell transplantation (HCT) of older or medically unfit patients, but successful outcome is still hindered by graft-versus-host disease (GVHD), especially in the setting of HLA-mismatched HCT. New GVHD prophylaxis strategies are emerging, including the triple drug strategy, that improve the GVHD-free and relapse-free survival (GRFS). Because the impact of ATG in HLA-mismatched Flu-TBI-based nonmyeloablative HCT has not been investigated, we did a retrospective analysis in three Dutch centers. 67 patients were evaluable, with a median age of 56 years. Overall survival, relapse-free survival and GRFS at 4 years were 52%, 43%, and 38%, respectively. NRM findings and cumulative incidence of relapse at 4 years were 26% and 31%, respectively. At 1-year grade II-IV had occurred in 40% of the patients, and the incidence of moderate-severe chronic GVHD incidence was 16%. Acknowledging the limitations of retrospective analyses, we conclude that the use of ATG for HLA-mismatched truly nonmyeloablative Flu-TBI HCT is feasible and results in acceptable long term outcomes, especially with regards to GRFS. We consider ATG in combination with cyclosporin and mycophenolate mofetil as an alternative for the triple drug strategy that uses sirolimus for GVHD prophylaxis in this particular setting.
Topics: Antilymphocyte Serum; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Middle Aged; Mycophenolic Acid; Retrospective Studies; Transplantation Conditioning; Transplantation, Homologous
PubMed: 34148060
DOI: 10.1038/s41409-021-01369-9 -
Archivio Italiano Di Urologia,... May 2024The rising prevalence of global end-stage renal disease (ESRD) is a significant health concern, especially among children. Although renal replacement therapy is...
INTRODUCTION
The rising prevalence of global end-stage renal disease (ESRD) is a significant health concern, especially among children. Although renal replacement therapy is available, children with ESRD are at an increased risk of mortality. Kidney transplantation is the preferred modality of treatment and surpasses renal replacement therapy in terms of survival. However, pediatric renal transplantation could prove difficult due to factors like smaller recipients and donor-recipient mismatches leading to higher complications.
MATERIALS AND METHODS
A retrospective single-group case series study was conducted on children with ESRD who were planned to undergo kidney transplantation from living donors between 2015 and 2021. The data was collected from two centers in the city of Sulaymaniyah.
RESULTS
The study comprised a predominantly male patient population, with a total of 39 individuals (n = 39) and 13 female patients. The donors were mostly males between 25-40 years old. The majority of participants were 15-18 years old. In majority of the patients Thymoglobulin was the immunosuppressive agent used in induction. The most common etiology for renal failure was reflux nephropathy and artery anastomosis was performed to the external iliac artery in the majority of patients. Only 9 patients had complications following the transplantation and 3 patients had an episode of acute rejection.
CONCLUSIONS
Renal transplantation is the preferred treatment of renal failure in pediatric patients in the city of Sulaymaniyah. The most common etiology for pediatric renal failure was reflux nephropathy which was different from the findings of North American Pediatric Renal Trials and Collaborative Studies.
Topics: Humans; Kidney Transplantation; Male; Female; Retrospective Studies; Adolescent; Child; Kidney Failure, Chronic; Immunosuppressive Agents; Adult; Living Donors; Child, Preschool; Postoperative Complications; Graft Rejection; Young Adult; Antilymphocyte Serum
PubMed: 38767870
DOI: 10.4081/aiua.2024.12389 -
Frontiers in Immunology 2024Acquired aplastic anemia (AA) is an immune-mediated bone marrow (BM) failure where marrow disruption is driven by a cytotoxic T-cell-mediated autoimmune attack against... (Review)
Review
Acquired aplastic anemia (AA) is an immune-mediated bone marrow (BM) failure where marrow disruption is driven by a cytotoxic T-cell-mediated autoimmune attack against hematopoietic stem cells. The key diagnostic challenge in children, but also in adults, is to exclude the possible underlying congenital condition and myelodysplasia. The choice of treatment options, either allogeneic hematopoietic cell transplantation (alloHCT) or immunosuppressive therapy (IST), depends on the patient's age, comorbidities, and access to a suitable donor and effective therapeutic agents. Since 2022, horse antithymocyte globulin (hATG) has been available again in Europe and is recommended for IST as a more effective option than rabbit ATG. Therefore, an update on immunosuppressive strategies is warranted. Despite an improved response to the new immunosuppression protocols with hATG and eltrombopag, some patients are not cured or remain at risk of aplasia relapse or clonal evolution and require postponed alloHCT. The transplantation field has evolved, becoming safer and more accessible. Upfront alloHCT from unrelated donors is becoming a tempting option. With the use of posttransplant cyclophosphamide, haploidentical HCT offers promising outcomes also in AA. In this paper, we present the state of the art in the management of severe AA for pediatric and adult patients based on the available guidelines and recently published studies.
Topics: Humans; Anemia, Aplastic; Hematopoietic Stem Cell Transplantation; Adult; Child; Immunotherapy; Antilymphocyte Serum; Immunosuppressive Agents; Treatment Outcome; Animals
PubMed: 38646536
DOI: 10.3389/fimmu.2024.1378432 -
Actas Urologicas Espanolas Mar 2021During the COVID-19 pandemic, the national transplant activity has been reduced due to the overload of the health system and concern for patient safety in this...
INTRODUCTION
During the COVID-19 pandemic, the national transplant activity has been reduced due to the overload of the health system and concern for patient safety in this situation. The aim of our work is to expose the activity of kidney transplantation in Cantabria during the state of alarm, as well as to assess the safety of the transplantation program.
MATERIAL AND METHODS
Retrospective study of kidney transplants performed in our Center from the beginning of the state of alarm until the beginning of the lockdown easing in Cantabria. Descriptive analysis of the demographic data of recipients and their donors, intraoperative data and postoperative outcomes. Comparative analysis with the data of the same period in 2017-2019, by means of the χ for categorical variables, Student's T and Mann-Whitney U tests in case of quantitative variables of normal and non-normal distribution, respectively.
RESULTS
Fifteen kidney transplants were performed in the period described. Delayed renal function (DRF) was seen in 7.5% of patients, and 26.6% showed data of acute rejection; no patient presented COVID-19 disease. Comparative analysis showed a remarkable increase in the number of transplants in comparison with previous periods (15 vs 5.6), at the expense of donors from outside Cantabria (93.3%). We found no statistically significant differences in terms of cold ischemia time (p=0.77), DRF (p=0.73), need for dialysis (p=0.54), or appearance of post-surgical complications (p=0.61).
CONCLUSIONS
The evolution of the pandemic in our region, and the adoption of strict protective measures has allowed the early and safe resumption of the renal transplantation program, increasing the number of transplants performed compared to previous years and maintaining comparable early post-operative results.
Topics: Adult; Antilymphocyte Serum; COVID-19; Cold Ischemia; Comorbidity; Diabetes Mellitus; Disease Susceptibility; Female; Graft Rejection; Humans; Hypertension; Immunosuppressive Agents; Kidney Diseases; Kidney Transplantation; Kidney Tubular Necrosis, Acute; Male; Middle Aged; Obesity; Pancreas Transplantation; Pandemics; Plasmapheresis; Renal Replacement Therapy; Reoperation; Retrospective Studies; Risk; Spain; Treatment Outcome
PubMed: 33213957
DOI: 10.1016/j.acuro.2020.10.002 -
Frontiers in Immunology 2022In haploidentical peripheral blood stem cell transplantation (haplo-PBSCT), the combination of anti-thymocyte globulin and post-transplant cyclophosphamide (ATG/PTCy)...
Modified combination of anti-thymocyte globulin (ATG) and post-transplant cyclophosphamide (PTCy) as compared with standard ATG protocol in haploidentical peripheral blood stem cell transplantation for acute leukemia.
In haploidentical peripheral blood stem cell transplantation (haplo-PBSCT), the combination of anti-thymocyte globulin and post-transplant cyclophosphamide (ATG/PTCy) has a synergistic impact in preventing graft-versus-host disease (GvHD). However, little is known about the long-term consequences of the new combination approach. Our goal is to evaluate the efficacy of ATG/PTCy versus a standard ATG regimen by focusing at long-term outcomes in a more homogeneous group of patients. We retrospectively included 118 adult patients up to 60 years with acute leukemia who underwent haplo-PBSCT at our single institution, following the same myeloablative conditioning regimen. From 2010 to 2020, 78 patients received a modified combination of ATG (2.5 mg/kg/day, on days -3, -2, and -1) and PTCy (40 mg/kg/day on days +3 and +4) compared to 40 patients who had a standard ATG-based regimen (2.5 mg/kg/day from days -4 to -1) from 2008 to 2015. The median follow-up time for all patients was 5.36 years, respectively. The cumulative incidence (CI) of neutrophil and platelet engraftment, as well as CMV reactivation, did not differ statistically between the two groups. The CI of the acute GvHD of grades II-IV and III-IV and extensive chronic GvHD were considerably lower in the ATG/PTCy (34.6%, 8.97%, and 13.63%) than in the ATG cohort (57.5%, 30%, and 38.23%) as validated by multivariable modeling. Additionally, compared to the ATG arm, the ATG/PTCy was a hazard factor associated with a higher risk of relapse (HR = 2.23, p = 0.039). The probability of 5-year overall survival, disease-free survival, and GvHD-free relapse-free survival in the ATG/PTCy group (53.34%, 49.77%, and 36.04%) was comparable with the ATG group (47.5%, 42.5%, and 22.5%), respectively. Our finding suggested that a modified ATG/PTCy combination resulted in a lower risk of acute and chronic GvHD and a higher risk of relapse than the standard ATG-based protocol but had no effect on long-term outcomes. However, certain adjustments in the immunosuppression protocol are warranted to improve the outcome.
Topics: Adult; Antilymphocyte Serum; Cyclophosphamide; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid, Acute; Peripheral Blood Stem Cell Transplantation; Retrospective Studies
PubMed: 35990618
DOI: 10.3389/fimmu.2022.921293