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Transplant Immunology Dec 2023Blood group B kidney transplant candidates have lower transplantation rates and longer waiting times compared to other blood groups. Kidney transplantation from blood...
Comparative analysis of Basiliximab and Alemtuzumab induction therapies in blood type A2-to-B kidney transplantation: Impact on kidney function and de novo donor-specific HLA antibodies.
PURPOSE
Blood group B kidney transplant candidates have lower transplantation rates and longer waiting times compared to other blood groups. Kidney transplantation from blood group A2-to-B has offered a solution for these patients. This study aimed to investigate the impact of Basiliximab and Alemtuzumab induction therapies on kidney function and de novo donor-specific antibodies (DSA) in blood type A2-to-B kidney transplant recipients within the first 12 months of post-transplant.
METHODS
A retrospective analysis was conducted on 110 consecutive A2-to-B kidney transplant recipients between January 2015 and December 2022. Of these, 46 (41.8%) received Basiliximab, while 64 (58.2%) received Alemtuzumab as induction therapy. Demographics and comorbidities data were collected and compared between the two groups. Serum samples collected at 4- and 12-month intervals post-transplant were used to assess the presence of de novo DSA. Kidney allograft function was evaluated by monitoring serum creatinine levels and assessing Creatinine Clearance based on 24-h urine collection at various time points.
RESULTS
During the follow-up period, 20.00% of patients who received Alemtuzumab developed de novo DSA, whereas none of the patients induced with Basiliximab developed de novo DSA (p = 0.038). Recipients who received Basiliximab were older (mean age = 72.00) and received higher Kidney Donor Profile Index (KDPI) kidneys (mean = 75) compared to those induced with Alemtuzumab (mean age = 58.00, mean KDPI = 49) (p < 0.001), with no significant difference observed in the last follow-up creatinine clearance or creatinine levels between the two groups (p = 0.28).
CONCLUSION
The use of Basiliximab as induction immunosuppression in A2-to-B kidney transplant recipients is associated with a lower incidence of de novo HLA DSA formation without significant differences in overall renal function compared to Alemtuzumab.
Topics: Humans; Aged; Middle Aged; Basiliximab; Alemtuzumab; Immunosuppressive Agents; Kidney Transplantation; Antibodies, Monoclonal; Retrospective Studies; Creatinine; Kidney; Blood Group Antigens; Graft Rejection; Graft Survival
PubMed: 37949378
DOI: 10.1016/j.trim.2023.101958 -
Multiple Sclerosis and Related Disorders Dec 2023To assess the differences of treatment outcomes regarding disease activity in patients with highly active relapsing multiple sclerosis (RMS), treated with autologous... (Observational Study)
Observational Study
OBJECTIVE
To assess the differences of treatment outcomes regarding disease activity in patients with highly active relapsing multiple sclerosis (RMS), treated with autologous hematopoietic stem cell transplantation (HSCT) or alemtuzumab (ATZ).
METHODS
Open-label prospective single-center observational cohort study, enrolling patients with highly active RMS for treatment with ATZ or HSCT between 2014 and 2021.
RESULTS
A total of 50 patients (31/50 (62 %) in HSCT vs 19/50 (38 %) in ATZ group) were included. There were no significant differences in relapse rate, MRI activity or disability worsening between the two study groups during the first two years after treatment onset. However, at 3 to 5 years follow-up, HSCT was superior to ATZ in all the aforementioned aspects. Kaplan-Meier analysis at 5 years post treatment revealed superiority of HSCT in relapse rate (69.6 % vs 95.7 %, p = 0.027), MRI activity (54.5 % vs 75.1 %, p = 0.038) and disability worsening (57.1 % vs 90.9 %, p = 0.031).
CONCLUSIONS
ATZ may halt disability progression early in the course of highly active RMS, but the disability starts accumulating later, while in HSCT patients disability improvement is consistent both 3 and 5 years after treatment onset.
Topics: Humans; Alemtuzumab; Multiple Sclerosis; Prospective Studies; Multiple Sclerosis, Relapsing-Remitting; Treatment Outcome; Hematopoietic Stem Cell Transplantation; Recurrence
PubMed: 37949024
DOI: 10.1016/j.msard.2023.105096 -
CEN Case Reports Jun 2024We report the first case of relapsing anti-GBM disease secondary to alemtuzumab in a 24-year-old female with relapsing-remitting multiple sclerosis. Initial anti-GBM...
We report the first case of relapsing anti-GBM disease secondary to alemtuzumab in a 24-year-old female with relapsing-remitting multiple sclerosis. Initial anti-GBM disease was detected 10 months after alemtuzumab was given and was diagnosed by demonstrating high anti-GBM antibody titers and with a confirmatory kidney biopsy. The patient presented with a rapidly progressive glomerulonephritis with no pulmonary involvement. After appropriate treatment, the patient went into remission with undetectable anti-GBM antibodies. However, 20 months later, the patient re-presented with relapsing anti-GBM disease. Despite aggressive treatment, the patient became dialysis-dependent.
Topics: Humans; Alemtuzumab; Female; Multiple Sclerosis, Relapsing-Remitting; Young Adult; Anti-Glomerular Basement Membrane Disease; Recurrence; Renal Dialysis; Kidney
PubMed: 37943475
DOI: 10.1007/s13730-023-00822-6 -
Bone Marrow Transplantation Jan 2024
Topics: Humans; Alemtuzumab; Steroids; Graft vs Host Disease; Immunosuppression Therapy; Recurrence; Hematopoietic Stem Cell Transplantation; Acute Disease
PubMed: 37932418
DOI: 10.1038/s41409-023-02144-8 -
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 -
[Rinsho Ketsueki] the Japanese Journal... 2023Chronic neutrophilic leukemia (CNL) is a clonal disorder that is characterized by increasing mature neutrophils. Colony stimulating factor 3 receptor (CSF3R) T618I...
Chronic neutrophilic leukemia (CNL) is a clonal disorder that is characterized by increasing mature neutrophils. Colony stimulating factor 3 receptor (CSF3R) T618I mutation was frequently identified in patients with CNL and is defined as a molecular marker of the disease. Ruxolitinib, a JAK2 inhibitor, provided a promising therapeutic effect in a phase II study. In particular, ruxolitinib was more efficient for patients with CSF3R mutation. Allogeneic stem cell transplantation (Allo-SCT) may be a curative treatment for CNL. On the other hand, further studies are needed to define the optimal method of transplantation, source of donor, conditioning therapy, and timing of transplantation. Chronic eosinophilic leukemia (CEL) is a clonal disorder that is characterized by increasing eosinophils. In the World Health Organization Classification 5th edition, diagnostic criteria for CEL are renewed. Because the new criteria will be more specific for CEL than criteria in the older edition, "not otherwise specified (NOS) " is removed from the name of the disease. Anti-CD52 antibody, alemtuzumab, or anti-IL-5 antibody, mepolizumab, are promising drugs to control symptoms that are associated with hypereosinophilic syndrome. Allo-SCT is anticipated as a curative treatment for CEL, but the evidence of Allo-SCT for CEL is still limited. Further study is required to define the treatment strategy.
Topics: Humans; Leukemia, Neutrophilic, Chronic; Mutation; Hypereosinophilic Syndrome; Leukemia, Myeloid
PubMed: 37914248
DOI: 10.11406/rinketsu.64.1326 -
Case Reports in Oncology 2023We present a case of lymphocytosis assumed and managed initially as a chronic lymphocytic leukemia. Shortly after initial visit, the patient's condition deteriorated...
We present a case of lymphocytosis assumed and managed initially as a chronic lymphocytic leukemia. Shortly after initial visit, the patient's condition deteriorated rapidly with hepatosplenomegaly, pleural effusion, ascites, and skin lesions. Flow cytometry (FC) showed the presence of clonal T-cell population, reported as T-cell lymphoma. Due to rapid clinical deterioration, urgent therapy with cyclophosphamide, doxorubicin, vincristine, etoposide, prednisone was initiated, but with minimal response. This prompted further diagnostic testing and demonstrated tumor cells positivity for CD3, CD30, and TCL1 markers. The diagnosis was changed to T-cell prolymphocytic leukemia. The patient responded well to alemtuzumab (anti-CD52 monoclonal antibody) and reached complete remission. FC is an essential modality for assessing and screening circulating lymphocytes when a lymphoproliferative disorder (LPD) is suspected. There are several LPDs that present with different degrees of clonal lymphocytosis. Reactive lymphocytosis should be appropriately investigated. Indolent LPDs can be surveyed by the internist or family physician, while more aggressive LPDs typically require management by hematologists.
PubMed: 37900812
DOI: 10.1159/000531592 -
Case Reports in Oncology 2023T-cell prolymphocytic leukemia (T-PLL) is a rare aggressive disease with a poor prognosis. Allogeneic stem cell transplantation (allo-SCT) followed by alemtuzumab...
T-cell prolymphocytic leukemia (T-PLL) is a rare aggressive disease with a poor prognosis. Allogeneic stem cell transplantation (allo-SCT) followed by alemtuzumab administration is the most promising treatment for T-PLL but is associated with a high risk of infections as alemtuzumab strongly suppresses cellular immunity, leading to high transplant-related mortality and unsatisfactory survival rates. In addition, for patients without human leukocyte antigen-matched donors, haploidentical stem cell transplantation (haplo-SCT) using post-transplant cyclophosphamide (PTCy) has been used because of the ready availability of donors and achievement of results comparable to those of transplantation with human leukocyte antigen-matched donors. However, there are no reports on the efficacy and safety, including infectious complications, of haplo-SCT with PTCy after alemtuzumab therapy in patients with. Here, we describe a 66-year-old Japanese male patient with T-PLL treated successfully with haplo-SCT after induction therapy of alemtuzumab for T-PLL. Approximately 3 months after the achievement of complete remission with alemtuzumab for T-PLL, haplo-SCT with reduced-intensity conditioning and PTCy was performed. Infectious complications were improved by early therapeutic interventions, and peripheral T cell counts gradually recovered. The patient was alive for more than 16 months after allo-SCT with no signs of relapse. Thus, haplo-SCT using PTCy should be considered as an option after alemtuzumab treatment for T-PLL.
PubMed: 37900793
DOI: 10.1159/000531471 -
Rheumatology International Feb 2024Pneumocystis jirovecii pneumonia (PJP) is a potentially fatal type of pneumonitis, which may have devastating consequences. Typically, it occurs in immunocompromised... (Review)
Review
Pneumocystis jirovecii pneumonia (PJP) is a potentially fatal type of pneumonitis, which may have devastating consequences. Typically, it occurs in immunocompromised patients, with the natural history varying depending on the presence or not of HIV infection. Staining and polymerase chain reaction (PCR) testing in induced sputum or bronchoalveolar lavage (BAL) is the cornerstone of the diagnosis, while trimethoprim-sulfamethoxazole is the treatment of choice. The etiological association of biologic agents with the occurrence of PJP is not entirely clear. Adalimumab is a fully human monoclonal anti-TNF-alpha antibody, which has been introduced relatively recently in the treatment of autoimmune inflammatory diseases, such as rheumatoid arthritis. In contrast to other biologic agents, such as Alemtuzumab or Infliximab, there are a small number of reports that support the drug's ability to trigger the occurrence of PJP. Hereby, we present a 53-year-old female patient with a medical history of rheumatoid arthritis on Adalimumab therapy, who developed PJP and we will discuss the main characteristics of PJP and the possible contribution of biologics to the occurrence of the infection.
Topics: Female; Humans; Middle Aged; Pneumonia, Pneumocystis; Adalimumab; Pneumocystis carinii; HIV Infections; Tumor Necrosis Factor Inhibitors; Arthritis, Rheumatoid
PubMed: 37851077
DOI: 10.1007/s00296-023-05483-3 -
Transplant Infectious Disease : An... Nov 2023Adenovirus (AdV) infection occurs in 0-20% of patients in the first 3-4 months after allogeneic hematopoietic cell transplantation (HCT), being higher in pediatric than... (Review)
Review
Adenovirus (AdV) infection occurs in 0-20% of patients in the first 3-4 months after allogeneic hematopoietic cell transplantation (HCT), being higher in pediatric than in adult patients. About 50% of AdV infections involve the blood, which in turn, correlates with an increased risk developing AdV diseases, end-organ damage, and 6-month overall mortality. The main risk factors for AdV infection are T-cell depletion of the graft by ex vivo selection procedures or in vivo use of alemtuzumab or antithymocyte serum, development of graft versus host disease (GVHD) grade III-IV, donor type (haploidentical or human leucocyte antigen mismatched related donor > cord blood> unrelated matched donor) and severe lymphopenia (<0.2 × 10 /L). The prevention of AdV disease relies on early diagnosis of increasing viral replication in blood or stool and the pre-emptive start of cidofovir as viral load exceeds the threshold of ≥10 copies/mL in blood and/or 10 copies/g stool in the stool. Cidofovir (CDV), a cytosine monophosphate nucleotide analog, is currently the only antiviral recommended for AdV infection despite limited efficacy and moderate risk of nephrotoxicity. Brincidofovir, a lipid derivative of CDV with more favorable pharmacokinetics properties and superior efficacy, is not available and currently is being investigated for other viral infections. The enhancement of virus-specific T-cell immunity in the first few months post-HCT by the administration of donor-derived or third-party-donor-derived virus-specific T-cells represents an innovative and promising modality of intervention and data of efficacy and safety of the ongoing prospective randomized studies are eagerly awaited.
Topics: Adult; Humans; Child; Cidofovir; Prospective Studies; Adenoviridae Infections; Risk Factors; Immunologic Factors; Hematopoietic Stem Cell Transplantation
PubMed: 37846850
DOI: 10.1111/tid.14173