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Journal of Pediatric Gastroenterology... May 2023The objectives of this study was to describe variation in induction regimen, identify predictors of induction immunosuppression (IS) choice, and examine the impact of...
OBJECTIVES
The objectives of this study was to describe variation in induction regimen, identify predictors of induction immunosuppression (IS) choice, and examine the impact of induction IS regimen on length of stay (LOS) and total perioperative costs in pediatric liver transplant recipients.
METHODS
We analyzed liver transplant utilization data in the Pediatric Health Information System database. Patients were divided into 3 induction IS groups: (1) steroids only, (2) T-cell depleting antibody (TDA), and (3) non-TDA. We identified predictors of induction IS regimen and examined associations between each outcome and choice of induction IS.
RESULTS
We analyzed 4905 liver transplant recipients (50% female, 80% under age 13 years, 42% non-Hispanic White). Most patients (3162, 64%) received steroids only induction, and about twice as many patients received a non-TDA regimen (1093, 22%) versus a TDA regimen (650, 13%). Median total perioperative costs were highest for the TDA group [$146,438 (interquartile range $113,461-$195,575)] versus the non-TDA group [$129,307 ($102,632-$173,953)] and the steroids only group ($127,049 ($98,814-$181,053)]. Compared to steroids only induction, TDA was associated with increased LOS (+2 days, P = 0.017) with no difference in cost. Non-TDA induction was associated with a decreased LOS (-3 days, P < 0.001) and increased cost (+$42,542; P < 0.001) independent of LOS.
CONCLUSIONS
Compared to a steroids only induction IS regimen, non-TDA induction was associated with increased total perioperative costs, even after adjustments for LOS. Future work will combine cost and outcome data to provide decision-making support in pediatric liver transplant recipients.
Topics: Humans; Female; Child; Adolescent; Male; Immunosuppressive Agents; Liver Transplantation; Graft Rejection; Immunosuppression Therapy; Antilymphocyte Serum; Steroids; Transplant Recipients
PubMed: 36735593
DOI: 10.1097/MPG.0000000000003728 -
Experimental and Clinical... Apr 2024Induction treatment in renal transplant is associated with better graft survival. However, intensified immunosuppression is known to cause unwanted side effects such as... (Comparative Study)
Comparative Study
OBJECTIVES
Induction treatment in renal transplant is associated with better graft survival. However, intensified immunosuppression is known to cause unwanted side effects such as infection and malignancy. Furthermore, the effects of the routine use of immunosuppressants in low-risk kidney transplant recipients are still not clear. In this study, we assessed the first-year safety and efficacy of induction treatment.
MATERIALS AND METHODS
We examined first living donor kidney transplant patients who were on tacrolimus based immunosuppression therapy. We formed 3 groups according to the induction status: antithymocyte globulin induction, basiliximab induction, and no induction. We collected outcome data on delayed graft function, graft loss, creatinine levels, estimated glomerular filtration rates, acute rejection episodes, hospitalization episodes, and infection episodes, including cytomegalovirus infection and bacterial infections.
RESULTS
We examined a total of 126 patients (age 35 ± 12 years; 65% male). Of them, 25 received antithymocyte globulin, 52 received basiliximab, and 49 did notreceive any induction treatment. We did not observe any statistically significant difference among the 3 groups in terms of acute rejection episodes, delayed graft function, and first-year graft loss. The estimated glomerular filtration rates were similar among the groups. Overall bacterial infectious complications and cytomegalovirus infection showed similar prevalence among all groups. Hospitalization was less common in the induction-free group.
CONCLUSIONS
In low-risk patients, induction-free regimens could be associated with a better safety profile without compromising graft survival. Therefore, induction treatment may be disregarded in first living donor transplant patients who receive tacrolimusbased triple immunosuppression treatment.
Topics: Adult; Female; Humans; Male; Middle Aged; Young Adult; Antilymphocyte Serum; Basiliximab; Calcineurin Inhibitors; Delayed Graft Function; Drug Therapy, Combination; Graft Rejection; Graft Survival; Immunosuppressive Agents; Kidney Transplantation; Living Donors; Recombinant Fusion Proteins; Retrospective Studies; Risk Factors; Tacrolimus; Time Factors; Treatment Outcome
PubMed: 38742317
DOI: 10.6002/ect.2023.0010 -
Bone Marrow Transplantation Jun 2020This collaborative initiative aimed to provide recommendations on the use of polyclonal antithymocyte globulin (ATG) or anti-T lymphocyte globulin (ATLG) for the... (Review)
Review
This collaborative initiative aimed to provide recommendations on the use of polyclonal antithymocyte globulin (ATG) or anti-T lymphocyte globulin (ATLG) for the prevention of graft-versus-host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (HSCT). A comprehensive review of articles released up to October, 2018 was performed as a source of scientific evidence. Fourteen clinically relevant key questions to the domains indication, administration, and post-transplant management were developed and recommendations were produced using the Delphi technique involving a Panel of 14 experts. ATG/ATLG was strongly recommended as part of myeloablative conditioning regimen prior to matched or mismatched unrelated bone marrow or peripheral blood allogeneic HSCT in malignant diseases to prevent severe acute and chronic GvHD. ATG/ATLG was also recommended prior to HLA-identical sibling peripheral HSCT with good but lesser bulk of evidence. In reduced intensity or nonmyeloablative conditioning regimens, ATG/ATLG was deemed appropriate to reduce the incidence of acute and chronic GvHD, but a higher risk of relapse should be taken into account. Recommendations regarding dose, application, and premedication were also provided as well as post-transplant infectious prophylaxis and vaccination. Overall, these recommendations can be used for a proper and safe application of polyclonal ATG/ATLG to prevent GvHD after allogeneic HSCT.
Topics: Animals; Antilymphocyte Serum; Consensus; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Neoplasm Recurrence, Local; Rabbits; Transplantation Conditioning
PubMed: 31969678
DOI: 10.1038/s41409-020-0792-x -
Annals of Hematology Oct 2023This is an observational multicentric cross-sectional study aiming at assessing the association between ABO blood groups and SARS-CoV-2 seroprevalence among the blood... (Observational Study)
Observational Study
This is an observational multicentric cross-sectional study aiming at assessing the association between ABO blood groups and SARS-CoV-2 seroprevalence among the blood donors in Puglia region. Data on ABO and Rh blood groups and demographic characteristics were obtained from Blood Bank Information System. All donors were screened for SARS-CoV-2 IgG antibodies. Comparison of seroprevalence among blood groups and the association between the recorded variables and seroprevalence were evaluated. A total of 35,709 donors from 22 centers were included, with a seroprevalence of 6.8%. The distribution of ABO phenotypes was blood type O (46.8%), A (34.0%), B (14.7%), and AB (4.5%). Among the 2416 donors reactive for SARS-CoV-2 IgG, the prevalent phenotype was blood type O (43.1%), followed by A (37.7%), B (14.2%), and AB (5%). The seroprevalence of phenotype A and AB was 7.5%, followed by B (6.5%) and O (6.2%). According to the adjusted analysis, there was an increase in seroprevalence in groups A and AB, compared to group O, and an increase in males compared to females. A possible effect modification was observed after stratifying for sex (p = 0.0515). A significantly lower prevalence of blood type O was found compared to A and AB, whereas no association was observed between Rh factor and seroprevalence. We hypothesized that the A antigen present in blood type A and AB can play a role in the binding of SARS-CoV-2 to ACE2 receptors, resulting in an increased risk of infection. Furthermore, natural anti-A/anti-B antibodies produced in group O could block viral adhesion to cells and explain a lower risk of infection.
Topics: Female; Male; Humans; Blood Donors; ABO Blood-Group System; COVID-19; SARS-CoV-2; Cross-Sectional Studies; Seroepidemiologic Studies; Antibodies, Viral; Antilymphocyte Serum; Immunoglobulin G
PubMed: 37442822
DOI: 10.1007/s00277-023-05331-1 -
BMC Nephrology Nov 2020Kidney allograft survival continuously improved with introduction of novel immunosuppressants. However, also immunologically challenging transplants (blood group...
BACKGROUND
Kidney allograft survival continuously improved with introduction of novel immunosuppressants. However, also immunologically challenging transplants (blood group incompatibility and sensitized recipients) increase. Between 2006 and 2008, a new tailored immunosuppression scheme for kidney transplantation was implemented at the University Hospital in Zurich, together with an ABO-incompatible transplant program and systematic pre- and posttransplant anti-human leukocyte antigen (HLA) antibody screening by Luminex technology. This study retrospectively evaluated the results of this tailored immunosuppression approach with a particular focus on immunologically higher risk transplants.
METHODS
A total of 204 consecutive kidney transplantations were analyzed, of whom 14 were ABO-incompatible and 35 recipients were donor-specific anti-HLA antibodies (DSA) positive, but complement-dependent cytotoxicity crossmatch (CDC-XM) negative. We analyzed patient and graft survival, acute rejection rates and infectious complications in ABO-compatible versus -incompatible and in DSA positive versus negative patients and compared those with a historical control group.
RESULTS
Overall patient, death-censored allograft survival and non-death-censored allograft survival at 4 years were 92, 91 and 87%, respectively. We found that (1) there were no differences between ABO-compatible and -incompatible and between DSA positive and DSA negative patients concerning acute rejection rate and graft survival; (2) compared with the historical control group there was a significant decrease of acute rejection rates in sensitized patients who received an induction with thymoglobulin; (3) there was no increased rate of infection among the patients who received induction with thymoglobulin compared to no induction therapy.
CONCLUSIONS
We observed excellent overall mid-term patient and graft survival rates with our tailored immunosuppression approach. Induction with thymoglobulin was efficient and safe in keeping rejection rates low in DSA positive patients with a negative CDC-XM.
Topics: Adult; Antilymphocyte Serum; Autoantibodies; Basiliximab; Blood Group Incompatibility; Drug Therapy, Combination; Female; Graft Rejection; Graft Survival; HLA Antigens; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Renal Insufficiency; Retrospective Studies; Rituximab; Survival Analysis; Transplantation Immunology
PubMed: 33228545
DOI: 10.1186/s12882-020-02137-5 -
Scientific Reports May 2023Allogeneic hematopoietic cell transplantation between female donors and male recipients (female-to-male allo-HCT) is a well-established risk factor for inferior survival...
Allogeneic hematopoietic cell transplantation between female donors and male recipients (female-to-male allo-HCT) is a well-established risk factor for inferior survival outcomes due to a higher incidence of graft-versus-host disease (GVHD). However, a clinical significance of anti-thymocyte globulin (ATG) in the female-to-male allo-HCT has not been elucidated. In this study, we retrospectively evaluated male patients who underwent allo-HCT between 2012 and 2019 in Japan. In the female-to-male allo-HCT cohort (n = 828), the use of ATG was not associated with a decreased risk of GVHD (HR of acute GVHD 0.691 [95% CI: 0.461-1.04], P = 0.074; HR of chronic GVHD 1.06 [95% CI: 0.738-1.52], P = 0.76), but was associated with favorable overall survival (OS) and a decreased risk of non-relapse mortality (NRM) (HR of OS 0.603 [95% CI: 0.400-0.909], P = 0.016; HR of NRM 0.506 [95% CI: 0.300-0.856], P = 0.011). The use of ATG in female-to-male allo-HCT resulted in survival outcomes that were almost equivalent to those in the male-to-male allo-HCT group. Therefore, GVHD prophylaxis with ATG might overcome the inferiority of survival outcomes in female-to-male allo-HCT.
Topics: Humans; Male; Female; Antilymphocyte Serum; Retrospective Studies; Hematopoietic Stem Cell Transplantation; Graft vs Host Disease; Tissue Donors; Transplantation Conditioning
PubMed: 37138004
DOI: 10.1038/s41598-023-34442-y -
BMC Medicine Aug 2019The optimal dose of rabbit antithymocyte globulin (ATG, ImtixSangstat) minimizing infections without increasing graft-versus-host disease (GVHD) is unknown in T... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The optimal dose of rabbit antithymocyte globulin (ATG, ImtixSangstat) minimizing infections without increasing graft-versus-host disease (GVHD) is unknown in T cell-replete, G-CSF-primed haploidentical hematopoietic stem cell transplantation (haplo-HSCT).
METHODS
Four hundred and eight patients were enrolled in this multicenter study to evaluate the effect of 7.5 mg/kg and 10.0 mg/kg rabbit ATG on viral infections and GVHD prophylaxis after haplo-HSCT. The primary endpoint was EBV DNAemia within 1 year posttransplantation.
RESULTS
The 1-year incidence of EBV DNAemia was 20.7% (95% confidence interval, 15.4-26.5) and 40.0% (33.3-46.6) in the 7.5 mg/kg and 10.0 mg/kg groups, respectively (P < 0.001). The 100-day cumulative incidence of grade II to IV aGVHD was 27.1% (21.1-33.4) and 25.4% (19.6-31.5) in the 7.5 mg/kg and 10.0 mg/kg ATG groups, respectively (P = 0.548). The 2-year incidence of chronic GVHD was 34.6% (27.8-41.4) and 36.2% (29.1-43.2) in the 7.5 mg and 10.0 mg groups (P = 0.814). The 1-year incidence of CMV DNAemia was 73.4% (67.2-79.4) and 83.4% (77.5-87.9) in the 7.5 mg/kg and 10.0 mg/kg groups (P = 0.038). The 3-year overall survival posttransplantation was 69.5% (63.2-75.8) and 63.5% (56.2-70.8), and the disease-free survival was 62.2% (55.3-69.1) and 60.3% (53.0-67.6) in the 7.5 mg/kg and 10.0 mg/kg groups, respectively (OS: P = 0.308; DFS: P = 0.660). The counts of EBV- and CMV-specific cytotoxic T cells (CTLs) were higher in the 7.5 mg/kg group than in the 10.0 mg/kg group early posttransplantation.
CONCLUSIONS
Compared with 10.0 mg/kg, 7.5 mg/kg ATG for GVHD prophylaxis was associated with reduced EBV and CMV infections without increased incidence of GVHD in haplo-HSCT, probably by affecting EBV- and CMV-specific CTLs.
TRIAL REGISTRATION
clinicaltrials.gov, NCT01883180 . Registered 14 June 2013.
Topics: Adolescent; Adult; Antilymphocyte Serum; Cytomegalovirus Infections; Disease-Free Survival; Dose-Response Relationship, Drug; Epstein-Barr Virus Infections; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Male; Middle Aged; Postoperative Complications
PubMed: 31401973
DOI: 10.1186/s12916-019-1393-7 -
Blood Cancer Journal Mar 2024There is an increased risk of GVHD and of non-relapse mortality (NRM) after allogeneic stem cell transplantations (alloSCT) when mismatched unrelated donors (MMUD) are...
There is an increased risk of GVHD and of non-relapse mortality (NRM) after allogeneic stem cell transplantations (alloSCT) when mismatched unrelated donors (MMUD) are used. In Europe, it is standard practice to use rabbit anti-thymocyte globulin (rATG) to reduce the high NRM and GVHD risks after MMUD alloSCT. As an alternative to rATG, post-transplantation Cyclophosphamide (PTCy) is in increasing clinical use. It is currently impossible to give general recommendations regarding preference for one method over another since comparative evidence from larger data sets is lacking. To improve the evidence base, we analyzed the outcome of rATG vs. PTCy prophylaxis in adult patients with hematologic malignancies undergoing first peripheral blood alloSCT from MMUD (9/10 antigen match) between Jan 2018 and June 2021 in the database of the European Society for Blood and Marrow Transplantation (EBMT). We performed multivariate analyses using the Cox proportional-hazards regression model. We included 2123 patients in the final analyses (PTCy, n = 583; rATG, n = 1540). p values and hazard ratios (HR) presented here are multivariate outcomes. Two years after alloSCT we found a lower NRM in the PTCy group of 18% vs. 24.9% in the rATG group; p = 0.028, HR 0.74. Overall survival in the PTCy cohort was higher with 65.7% vs. 55.7% in the rATG cohort; p < 0.001, HR 0.77. Progression-free survival was also better in the PTCy patients with 59.1% vs. 48.8% when using rATG; p = 0.001, 0.78. The incidences of chronic GVHD and acute GVHD were not significantly different between the groups. We found significantly lower NRM as well as higher survival in recipients of peripheral blood alloSCTs from MMUD receiving PTCy as compared to rATG. The results of the current analysis suggest an added value of PTCy as GVHD prophylaxis in MMUD alloSCT.
Topics: Adult; Humans; Neoplasm Recurrence, Local; Hematopoietic Stem Cell Transplantation; Cyclophosphamide; Graft vs Host Disease; Antilymphocyte Serum; Unrelated Donors; Retrospective Studies
PubMed: 38485723
DOI: 10.1038/s41408-024-01032-8 -
Haematologica Jun 2021Graft-versus-host disease (GVHD) prophylaxis for unmanipulated haploidentical hematopoietic cell transplantation (haplo-HCT) include post-transplant cyclophosphamide...
Post-transplant cyclophosphamide versus anti-thymocyte globulin for graft-versus-host disease prevention in haploidentical transplantation for adult acute lymphoblastic leukemia.
Graft-versus-host disease (GVHD) prophylaxis for unmanipulated haploidentical hematopoietic cell transplantation (haplo-HCT) include post-transplant cyclophosphamide (PTCy) and anti-thymocyte globulin (ATG). Utilizing EBMT registry, we compared ATG versus PTCy based GVHD prophylaxis in adult acute lymphoblastic leukemia (ALL) patients undergoing haplo-HCT. Included were 434 patients; ATG (n=98) and PTCy (n=336). Median follow-up was ~2 years. Baseline characteristics were similar between the groups except that the ATG-group was more likely to have relapsed/refractory ALL (P=0.008), non-TBI conditioning (P<0.001), peripheral blood graft source (P=<0.001) and transplanted at an earlier time-period (median year of HCT 2011 vs. 2015). The 100-day grade II-IV and III-IV acute-GVHD was similar between ATG and PTCy, as was 2-year chronic-GVHD. On multivariate analysis (MVA), leukemia-free survival (LFS) and overall survival (OS) was better with PTCy compared to ATG prophylaxis. Relapse incidence (RI) was lower in the PTCy group (P=0.03), while non-relapse mortality (NRM) was not different. Advanced disease and lower performance score were associated with poorer LFS and OS and advanced disease with inferior GVHD-free/relapse-free survival (GRFS). Peripheral grafts were associated with higher GVHD compared to bone marrow grafts. In ALL patients undergoing unmanipulated haplo-HCT, PTCy for GVHD prevention resulted in lower RI and improved LFS and OS compared to ATG.
Topics: Adult; Antilymphocyte Serum; Cyclophosphamide; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Transplantation Conditioning; Transplantation, Haploidentical
PubMed: 32354866
DOI: 10.3324/haematol.2020.247296 -
Bone Marrow Transplantation Apr 2024Allogeneic hematopoietic stem cell transplantation (alloHSCT) remains the only curative treatment for myelofibrosis (MF). Relapse occurs in 10-30% and remains a major...
Allogeneic hematopoietic stem cell transplantation (alloHSCT) remains the only curative treatment for myelofibrosis (MF). Relapse occurs in 10-30% and remains a major factor for dismal outcomes. Previous work suggested that graft-versus-host disease (GVHD) might be associated with risk of relapse. This study included 341 patients undergoing their first (n = 308) or second (n = 33) alloHSCT. Anti-T-lymphocyte or antithymocyte globulin was used for GVHD prophylaxis in almost all patients. Median time to neutrophile and platelet engraftment was 13 days and 19 days, respectively. The cumulative incidence of acute GVHD grade II-IV was 41% (median, 31 days; range, 7-112). Grade III-IV acute GVHD was observed in 22%. The cumulative incidence of chronic GVHD was 61%. Liver was affected in 23% of acute GVHD cases and 46% of chronic GVHD cases. Severe acute GVHD was associated with high non-relapse mortality. The development of acute GVHD grade II and moderate GVHD was an independent factor for reduced risk for relapse after transplantation without increased risk for non-relapse mortality, while especially acute GVHD grade IV was associated with high non-relapse mortality. Last, we identified that ongoing response to ruxolitinib, accelerated-phase MF at time of transplantation and splenectomy prior to transplantation were independent predictors for relapse.
Topics: Humans; Primary Myelofibrosis; Neoplasm Recurrence, Local; Hematopoietic Stem Cell Transplantation; Graft vs Host Disease; Antilymphocyte Serum
PubMed: 38321269
DOI: 10.1038/s41409-024-02220-7