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American Journal of Kidney Diseases :... Jun 2024Kidney transplant patients with glomerulonephritis (GN) as their native disease commonly have received pretransplant immunosuppression (PTI). This may contribute to the...
RATIONALE & OBJECTIVE
Kidney transplant patients with glomerulonephritis (GN) as their native disease commonly have received pretransplant immunosuppression (PTI). This may contribute to the immunosuppression burden potentially increasing the risk for infections after transplantation.
STUDY DESIGN
Single-center, retrospective cohort study.
SETTING & PARTICIPANTS
Recipients of a kidney transplant from January 2005 until May 2020 at a tertiary care university teaching hospital.
EXPOSURE
Patients with GN as their native kidney disease who received PTI for treatment of GN (n=184) were compared with nondiabetic recipients of kidney transplants who did not receive PTI (n = 579).
OUTCOME
First occurrence after transplantation of an infection outcome, either viral (BK or cytomegalovirus [CMV] infection) or bacterial.
ANALYTICAL APPROACH
Cox regression analysis adjusted for age at transplant, sex, race, donor type, year of transplant surgery, dialysis vintage, receipt of T-cell depleting induction, and CMV transplant status.
RESULTS
Over a median follow-up period of 5.7 years, patients with GN PTI were not at an increased risk for developing any first viral infection compared with controls (adjusted HR [AHR] 0.69 [95% CI, 0.52-0.91]) nor at increased risk for specific viral infections: BK infection 19.6% vs 26.3% (AHR 0.72 [95% CI, 0.50-1.05]) or CMV infection, 24.5% vs 29.0% (AHR, 0.76 [95% CI, 0.54-1.07]), respectively. There was also no increased risk of developing a first bacterial infection: 54.5% vs 57.5% (AHR, 0.90 [95% CI, 0.71-1.13]). These findings of no increased risk for infection were independent of the type of PTI used (cyclophosphamide, rituximab, mycophenolate mofetil, or calcineurin inhibitor) or the type of T-cell depleting induction therapy (alemtuzumab or antithymocyte globulin) administered.
LIMITATIONS
Single-center study, no data on methylprednisone use for PTI, unmeasured confounding.
CONCLUSIONS
Use of PTI for the treatment of GN was not associated with an increased risk of viral (BK or CMV) or bacterial infection after transplantation. Additional surveillance for infection after transplantation for patients who received PTI may not be necessary.
PLAIN-LANGUAGE SUMMARY
Many kidney transplant patients have glomerular disease as the cause of kidney failure. These patients may be exposed to immunosuppression before transplantation, which could increase the risk for infections after receipt of a transplanted kidney. We identified kidney transplant recipients at a university teaching hospital who received immunosuppression before transplant for the treatment of glomerular kidney disease. We examined their risk for infection after transplantation by comparing it with the risk among transplant patients who were not exposed to immunosuppression before transplant. We observed no increased risk for infection after exposure to prior immunosuppression. Therefore, patients exposed to significant amounts of immunosuppression before transplantation may not require special surveillance or medication adjustment for fear of infection after their receipt of a kidney transplant.
Topics: Humans; Kidney Transplantation; Male; Female; Glomerulonephritis; Retrospective Studies; Middle Aged; Immunosuppressive Agents; Adult; Cytomegalovirus Infections; Immunosuppression Therapy; Bacterial Infections; Postoperative Complications
PubMed: 38160700
DOI: 10.1053/j.ajkd.2023.10.016 -
Transplantation and Cellular Therapy Mar 2024Data comparing hematopoietic stem cell transplantation (HSCT) using bone marrow (BM) or peripheral blood stem cell (PBSC) grafts in children after alemtuzumab-based...
Alemtuzumab, Dual Graft-versus-Host Disease Prophylaxis, and Lower CD3 T Cell Doses Equalize Rates of Acute and Chronic Graft-versus-Host Disease in Pediatric Patients Receiving Allogeneic Hematopoietic Stem Cell Transplantation with Matched Unrelated Donor Peripheral Blood Stem Cells or Bone...
Data comparing hematopoietic stem cell transplantation (HSCT) using bone marrow (BM) or peripheral blood stem cell (PBSC) grafts in children after alemtuzumab-based conditioning are lacking. We investigated whether in vivo T cell depletion using alemtuzumab could reduce the risk of severe acute graft-versus-host disease (aGVHD) and chronic GVHD (cGVHD) after HSCT with matched unrelated donor (MUD) BM or PBSCs. This retrospective multicenter study included 397 children (BM group, n = 202; PBSC group, n = 195) who underwent first MUD HSCT at 9 pediatric centers in the United Kingdom between 2015 and 2019. The median age at transplantation was 7.0 years (range, .1 to 19.3 years), and the median duration of follow-up was 3.1 years (range, .3 to 7.5 years). The 3-year overall survival was 81% for the entire cohort (BM group, 80%; PBSC group, 81%). The incidence of grade II-IV aGVHD was significantly higher in the PBSC group (31%) compared to the BM group (31% versus 19%; P = .003), with no difference in the incidence of grade III-IV aGVHD (BM, 7%; PBSC, 12%; P = .17). CD3 T cell dose >5 × 10/kg and the use of PBSCs were independent predictors of grade II-IV aGVHD. When considering CD3 T cell dose and GVHD prophylaxis, PBSC transplantation with a calcineurin inhibitor (CNI) and mycophenolate mofetil (MMF) and a CD3 T cell dose ≤5 × 10/kg had a comparable grade II-IV aGVHD to BM transplantation plus a CNI (20% versus 18%; P = .52). PBSC transplantation was associated with a lower incidence of cGVHD compared to BM transplantation (6% versus 11%; P = .03). Within the limits of this study, we identified a potential strategy to reduce the risk of severe GVHD in pediatric PBSC recipients that includes a combination of in vivo T cell depletion using alemtuzumab and dual GVHD prophylaxis (with a CNI and MMF) and limiting the CD3 T cell dose to ≤5 × 10/kg.
Topics: Adolescent; Child; Child, Preschool; Humans; Infant; Young Adult; Alemtuzumab; Bone Marrow; Bronchiolitis Obliterans Syndrome; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Peripheral Blood Stem Cells; T-Lymphocytes; Unrelated Donors
PubMed: 38103787
DOI: 10.1016/j.jtct.2023.12.005 -
Clinical Case Reports Nov 2023Here, we present a case of relapsing-remitting multiple sclerosis that experienced petechiae and epistaxis following treatment with second dose of alemtuzumab. This...
Here, we present a case of relapsing-remitting multiple sclerosis that experienced petechiae and epistaxis following treatment with second dose of alemtuzumab. This study highlights such effects, emphasizing the need for vigilance as alemtuzumab usage increases. Timely recognition and management are vital for patient care.
PubMed: 38028047
DOI: 10.1002/ccr3.8143 -
Transplant International : Official... 2023Alemtuzumab is used as lymphocyte-depleting therapy for severe or glucocorticoid-resistant kidney transplant rejection. However, the long-term efficacy and toxicity of...
Alemtuzumab is used as lymphocyte-depleting therapy for severe or glucocorticoid-resistant kidney transplant rejection. However, the long-term efficacy and toxicity of alemtuzumab therapy are unclear. Therefore, all cases of alemtuzumab anti-rejection therapy between 2012 and 2022 in our institution were investigated. Graft survival, graft function, lymphocyte depletion, serious infections, malignancies, and patient survival were analyzed and compared with a reference cohort of transplanted patients who did not require alemtuzumab anti-rejection therapy. A total of 225 patients treated with alemtuzumab were identified and compared with a reference cohort of 1,668 patients. Over 60% of grafts was salvaged with alemtuzumab therapy, but graft survival was significantly poorer compared to the reference cohort. The median time of profound T- and B lymphocyte depletion was 272 and 344 days, respectively. Serious infection rate after alemtuzumab therapy was 54.1/100 person-years. The risk of death (hazard ratio 1.75, 95%-CI 1.28-2.39) and infection-related death (hazard ratio 2.36, 95%-CI 1.35-4.11) were higher in the alemtuzumab-treated cohort. In conclusion, alemtuzumab is an effective treatment for severe kidney transplant rejection, but causes long-lasting lymphocyte depletion and is associated with frequent infections and worse patient survival outcomes.
Topics: Humans; Alemtuzumab; Immunosuppressive Agents; Glucocorticoids; Kidney Transplantation; Antibodies, Monoclonal, Humanized; Graft Survival; Graft Rejection
PubMed: 38020744
DOI: 10.3389/ti.2023.11834 -
Pharmaceuticals (Basel, Switzerland) Nov 2023(1) Background: The purpose of study was to compare the safety profile of glatiramer with natalizumab, alemtuzumab and ocrelizumab in pregnant and lactating women...
(1) Background: The purpose of study was to compare the safety profile of glatiramer with natalizumab, alemtuzumab and ocrelizumab in pregnant and lactating women affected by multiple sclerosis (MS). (2) Methods: Individual case safety reports (ICSRs) were retrieved from the European spontaneous reporting system database (EudraVigilance). The reporting odds ratios (RORs) were computed to compare the reporting probability of events between natalizumab, alemtuzumab and ocrelizumab vs. glatiramer. (3) Results: A total of 1236 ICSRs reporting at least one DMT as a suspected drug were selected. More adverse drug reactions (ADRs) unrelated to pregnancy and breastfeeding ( = 1171; 32.6%) were reported than ADRs specific to pregnancy and breastfeeding ( = 1093; 30.4%). The most frequently reported unrelated ADR was MS relapse. Alemtuzumab and natalizumab seem to have a lower reporting probability of MS relapse compared to glatiramer (ROR 0.17, 95% CI 0.07-0.45 and ROR 0.34, 95% CI 0.20-0.57). Among pregnancy- and breastfeeding-related ADRs, the first most reported event was spontaneous abortion ( = 321; 8.9%). Natalizumab and ocrelizumab were associated with a higher reporting probability of spontaneous abortion compared to glatiramer (ROR 2.22, 95% CI 1.58-3.12; ROR 2.18, 95% CI 1.34-3.54, respectively), while alemtuzumab had a lower reporting frequency (ROR 0.32, 95% CI 0.17-0.60). (4) Conclusions: This study did not suggest any strong or new insights for DMTs in this special subpopulation. However, further studies need to be performed.
PubMed: 38004432
DOI: 10.3390/ph16111566 -
Current Oncology (Toronto, Ont.) Nov 2023T-prolymphocytic leukemia (T-PLL) is a rare malignancy of mature T-cells with distinct clinical, cytomorphological, and molecular genetic features. The disease typically... (Review)
Review
T-prolymphocytic leukemia (T-PLL) is a rare malignancy of mature T-cells with distinct clinical, cytomorphological, and molecular genetic features. The disease typically presents at an advanced stage, with marked leukocytosis, B symptoms, hepatosplenomegaly, and bone marrow failure. It usually follows an aggressive course from presentation, and the prognosis is often considered dismal; the median overall survival is less than one year with conventional chemotherapy. This case report describes a patient with T-PLL who, after an unusually protracted inactive phase, ultimately progressed to a highly invasive, organ-involving disease. After initial treatments failed, a novel treatment approach resulted in a significant response.
Topics: Humans; Alemtuzumab; Leukemia, Prolymphocytic; Leukemia, Prolymphocytic, T-Cell
PubMed: 37999147
DOI: 10.3390/curroncol30110727 -
Cells Nov 2023In recent years, targeted (biological) therapies have become available also for primary cutaneous T-cell lymphomas (PCTCLs) including anti-CD30 (brentuximab vedotin) in... (Review)
Review
In recent years, targeted (biological) therapies have become available also for primary cutaneous T-cell lymphomas (PCTCLs) including anti-CD30 (brentuximab vedotin) in mycosis fungoides, primary cutaneous anaplastic large T-cell lymphoma, lymphomatoid papulosis; anti-CCR4 (mogamulizumab) in Sezary syndrome; anti-CD123 (tagraxofusp) in blastic plasmocytoid cell neoplasm. Moreover, anti-PD1 (nivolumab), anti-PDL1 (pembrolizumab, atezolizumab), anti-CD52 (alemtuzumab), anti-KIR3DL2-CD158k (lacutamab), and anti-CD70 (cusatuzumab) have been tested or are under investigations in phase II trials. The expression of these epitopes on neoplastic cells in skin biopsies or blood samples plays a central role in the management of PCTCL patients. This narrative review aims to provide readers with an update on the latest advances in the newest therapeutic options for PCTCLs.
Topics: Humans; Skin Neoplasms; Mycosis Fungoides; Brentuximab Vedotin; Sezary Syndrome; Antineoplastic Agents; Antibodies, Monoclonal
PubMed: 37998391
DOI: 10.3390/cells12222656 -
Neurologia 2023This article analyses the presence of gender bias in clinical trials of monoclonal antibodies used to treat multiple sclerosis. (Review)
Review
INTRODUCTION
This article analyses the presence of gender bias in clinical trials of monoclonal antibodies used to treat multiple sclerosis.
MATERIAL AND METHODS
We performed a systematic review of controlled clinical trials of 4 monoclonal antibodies used to treat multiple sclerosis (natalizumab, rituximab, alemtuzumab, and ocrelizumab). We searched the PubMed/MEDLINE database for articles published in English before March 2020. The study was conducted in accordance with the relevant international recommendations.
RESULTS
The search identified 89 articles, 55 of which met the inclusion criteria. Of all patients included in these trials, 64.6% were women. The lead authors of 10 of the studies were women. Fifteen of the 55 studies included a sex-based analysis of the primary endpoint. Only 8 articles discussed the results separately for men and for women.
CONCLUSIONS
The clinical trials of these 4 monoclonal antibodies present a significant gender bias. In most cases, the primary and secondary endpoints are not analyzed according to patient sex, despite the fact that international recommendations include this as a minimum requirement for ensuring scientific validity and obtaining appropriate results for extrapolation to the wider population.
Topics: Humans; Female; Male; Antibodies, Monoclonal; Multiple Sclerosis; Sexism; Alemtuzumab; Rituximab
PubMed: 37996214
DOI: 10.1016/j.nrleng.2021.01.008 -
Journal of Biomedical Informatics Dec 2023Computational models are at the forefront of the pursuit of personalized medicine thanks to their descriptive and predictive abilities. In the presence of complex and...
OBJECTIVE
Computational models are at the forefront of the pursuit of personalized medicine thanks to their descriptive and predictive abilities. In the presence of complex and heterogeneous data, patient stratification is a prerequisite for effective precision medicine, since disease development is often driven by individual variability and unpredictable environmental events. Herein, we present GreatNectorworkflow as a valuable tool for (i) the analysis and clustering of patient-derived longitudinal data, and (ii) the simulation of the resulting model of patient-specific disease dynamics.
METHODS
GreatNectoris designed by combining an analytic strategy composed of CONNECTOR, a data-driven framework for the inspection of longitudinal data, and an unsupervised methodology to stratify the subjects with GreatMod, a quantitative modeling framework based on the Petri Net formalism and its generalizations.
RESULTS
To illustrate GreatNectorcapabilities, we exploited longitudinal data of four immune cell populations collected from Multiple Sclerosis patients. Our main results report that the T-cell dynamics after alemtuzumab treatment separate non-responders versus responders patients, and the patients in the non-responders group are characterized by an increase of the Th17 concentration around 36 months.
CONCLUSION
GreatNectoranalysis was able to stratify individual patients into three model meta-patients whose dynamics suggested insight into patient-tailored interventions.
Topics: Humans; Workflow; Computer Simulation; Precision Medicine; Cluster Analysis
PubMed: 37984546
DOI: 10.1016/j.jbi.2023.104546