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Ophthalmic Plastic and Reconstructive...To present 5 cases of alemtuzumab-induced thyroid eye disease (AI-TED) and review the literature to highlight the natural history, severity, and outcomes as compared... (Review)
Review
PURPOSE
To present 5 cases of alemtuzumab-induced thyroid eye disease (AI-TED) and review the literature to highlight the natural history, severity, and outcomes as compared with conventional thyroid eye disease (TED).
METHODS
A multi-institutional retrospective case series of patients with AI-TED was compiled. Chart review evaluated for clinical characteristics, imaging findings, and treatment for AI-TED. Additionally, a comprehensive review of the literature identified all previously published cases of AI-TED.
RESULTS
Five new patients with AI-TED were included in this series. The average clinical activity score on presentation was 2.8 (range 1-4) and reached an average peak of 5.0 during the active phase of the disease (4-7). Patients were treated medically with selenium (40%) or monoclonal antibodies including teprotumumab or tocilizumab (40%). Surgical treatment with orbital decompression for compressive optic neuropathy was performed on 2 (40%) patients. Combined with 11 previously reported cases, these 16 patients with AI-TED had an average clinical activity score on presentation of 3.3. The average length of the AI-TED phase was 14.0 months, and all patients were treated with medical and/or surgical interventions for their disease.
CONCLUSIONS
Clinical and imaging findings in AI-TED mirror that of conventional TED, however, AI-TED may present with greater severity. AI-TED may develop many months after Graves' disease; therefore, providers should be aware of this association and monitor patients for the development of severe TED.
Topics: Humans; Graves Ophthalmopathy; Alemtuzumab; Retrospective Studies; Graves Disease; Optic Nerve Diseases
PubMed: 36893061
DOI: 10.1097/IOP.0000000000002367 -
Pediatrics International : Official... 2023
Topics: Humans; Alemtuzumab; Lymphoproliferative Disorders; Genetic Diseases, X-Linked; Hematopoietic Stem Cell Transplantation; Transplantation Conditioning; Graft vs Host Disease; X-Linked Inhibitor of Apoptosis Protein
PubMed: 37534620
DOI: 10.1111/ped.15576 -
Journal of Neuroimmunology May 2023Immune responses in the central nervous system (CNS) are highly compartmentalized and cerebrospinal fluid (CSF) in particular often reflects CNS pathology better than...
BACKGROUND AND OBJECTIVES
Immune responses in the central nervous system (CNS) are highly compartmentalized and cerebrospinal fluid (CSF) in particular often reflects CNS pathology better than peripheral blood. While CSF leukocytes are known to be distinct from blood, the immediate effects of peripheral leukocyte depletion on CSF leukocytes have not been studied in humans.
METHODS
We here analyzed CSF and blood from two relapsing-remitting multiple sclerosis (RRMS) patients early after peripheral leukocyte depletion with the anti-CD52 antibody alemtuzumab compared to untreated RRMS and control patients using single cell RNA-sequencing.
RESULTS
As expected for alemtuzumab, most leukocyte lineages including T cells were synchronously depleted from CSF and blood, while - surprisingly - pDCs were maintained in CSF but depleted from blood by alemtuzumab. Transcriptionally, genes associated with migration were elevated only in the CSF after alemtuzumab. Predicted cellular interactions indicated a central role of pDCs and enhanced migration signaling in the CSF after alemtuzumab.
DISCUSSION
The CSF and blood compartments are thus partially uncoupled, emphasizing that the CNS is only partially accessible even for treatments profoundly affecting the blood.
Topics: Humans; Alemtuzumab; Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Central Nervous System
PubMed: 37062182
DOI: 10.1016/j.jneuroim.2023.578088 -
Pediatric Transplantation Aug 2021We studied the association of induction immunosuppression and pediatric deceased-donor kidney recipient and graft survival.
BACKGROUND
We studied the association of induction immunosuppression and pediatric deceased-donor kidney recipient and graft survival.
METHODS
We utilized the SRTR to evaluate all primary pediatric deceased-donor kidney transplants from January 1st, 2000, through December 2018. We included only recipients who were maintained on tacrolimus and mycophenolate. Recipients were grouped by induction type: alemtuzumab n = 320, r-ATG n = 2091 and IL-2RA n = 2165. Recipient and allograft survival, and their predictors, were examined. Models were adjusted for age, sex, ethnicity, HLA-antigen mismatches, transplant year, steroid maintenance, pre-emptive transplantation and payor type, with the transplant center included as a random effect.
RESULTS
Rejection rates at 6 months (alemtuzumab 8.6% vs r-ATG 7.8% vs IL2-RA 9.2%; P = .30) and 12 months (alemtuzumab 17.2% vs r-ATG 15.7% vs IL2-RA 16.5%; P = .70) were not significantly different between induction groups. In the multivariable models, compared to IL-2RA neither alemtuzumab nor r-ATG was associated with improved recipient [alemtuzumab (HR 1.06, P = .88); r-ATG (HR 1.03, P = .84)] or graft survival [alemtuzumab (HR 1.18, P = .32); r-ATG (HR 1.10, P = .21)].
CONCLUSION
In this large cohort of standard immunological risk primary pediatric deceased-donor kidney recipients on tacrolimus and mycophenolate maintenance, depletional induction regimens were not associated with better rejection rates, recipient, or graft survival compared to IL-2RA induction. Racial, payor type, and sex-related outcome disparities were significant in this group independent of the induction choice.
Topics: Adolescent; Alemtuzumab; Antilymphocyte Serum; Child; Child, Preschool; Female; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Infant; Interleukin-2 Receptor alpha Subunit; Kidney Transplantation; Male; Mycophenolic Acid; Risk Factors; Tacrolimus; United States
PubMed: 33314638
DOI: 10.1111/petr.13928 -
European Journal of Neurology Mar 2022Alemtuzumab, a monoclonal anti-CD52 antibody, and cladribine, a purine nucleoside analogue, are used for the treatment of highly active relapsing-remitting multiple...
BACKGROUND AND PURPOSE
Alemtuzumab, a monoclonal anti-CD52 antibody, and cladribine, a purine nucleoside analogue, are used for the treatment of highly active relapsing-remitting multiple sclerosis (MS). Both are administered as two short yearly courses but possess the ability to induce long-term remission, labeling them as immune reconstitution therapies. Although disease activity after alemtuzumab administration is rare, there are a small number of people with MS who will experience disease activity despite repeated alemtuzumab treatment.
METHODS
We report on six patients with MS who experienced disease activity after alemtuzumab and were subsequently treated with cladribine and followed up for up to 2 years.
RESULTS
None of the patients experienced relapses during the follow-up period and in all patients Expanded Disability Status Scale values remained unchanged. All patients had lymphopenia at one time point. In patients 1 and 2, at the nadir, the lymphopenia was grade 1, in patient 3 it was grade 2 and in patients 5 and 6 it was grade 3. No infections or malignancies were recorded during the follow-up.
CONCLUSION
This report provides a framework for treating people with MS with sequential immune reconstitution therapies.
Topics: Alemtuzumab; Cladribine; Humans; Immune Reconstitution; Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting
PubMed: 34676950
DOI: 10.1111/ene.15153 -
Medicine Feb 2018Multiple sclerosis (MS) is an autoimmune disease, in which the insulating covers of nerve cells in the brain and spinal cord are demyelinated. This study was conducted...
BACKGROUND
Multiple sclerosis (MS) is an autoimmune disease, in which the insulating covers of nerve cells in the brain and spinal cord are demyelinated. This study was conducted to compare the efficacy of alemtuzumab and natalizumab in the treatment of different stages of MS patients.
METHODS
A total of 585 patients diagnosed with MS and hospitalized were included and analyzed after which they were divided into the primary progressive MS A and B groups, the relapsing-remitting MS (RRMS) C and D groups, and the secondary progressive MS E and F groups. Patients in A, C, and E groups were administered alemtuzumab while those in B, D, and F groups were administered natalizumab for the treatment. The expanded disability status scale (EDSS) scores and the EDSS difference were calculated before and after treatment. The number of head magnetic resonance imaging enhanced lesions in the patients, recurrence time and recurrence rate were measured before and after treatment.
RESULTS
The EDSS score of the RRMS group was significantly lower than that of the primary progressive MS group and the secondary progressive MS group. After 12 months of treatment, the EDSS score of RRMS patients treated with natalizumab was significantly lower compared with the patients with alemtuzumab, and the difference before and after treatment was significantly higher than alemtuzumab. The recurrence rate of the RRMS-D group was significantly lower than the RRMS-C group. After 12 months of treatment, compared with the RRMS-C group, a significant reduction was observed in the number of head magnetic resonance imaging enhanced lesions and longer recurrence time in the RRMS-D group.
CONCLUSION
The efficacy of natalizumab was better than alemtuzumab in the treatment of patients in the RRMS group, while there was no significant difference among other stages of MS patients, which provided the theoretical basis and clinical guidance for the treatment of different stages of MS.
Topics: Adult; Alemtuzumab; Female; Humans; Immunologic Factors; Magnetic Resonance Imaging; Male; Multiple Sclerosis, Chronic Progressive; Multiple Sclerosis, Relapsing-Remitting; Natalizumab; Treatment Outcome; Young Adult
PubMed: 29465579
DOI: 10.1097/MD.0000000000009908 -
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 -
Neurological Sciences : Official... Sep 2022
Topics: Alemtuzumab; Humans; Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Myelodysplastic Syndromes
PubMed: 35543831
DOI: 10.1007/s10072-022-06124-6 -
Brain : a Journal of Neurology Jun 2022
Topics: Alemtuzumab; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Autoimmunity; Clone Cells; Humans
PubMed: 35661862
DOI: 10.1093/brain/awac162 -
Frontiers in Immunology 2020Rabbit anti-thymocyte globulin (rATG) is currently the treatment of choice for glucocorticoid-resistant, recurrent, or severe acute allograft rejection (AR). However,... (Comparative Study)
Comparative Study
Rabbit anti-thymocyte globulin (rATG) is currently the treatment of choice for glucocorticoid-resistant, recurrent, or severe acute allograft rejection (AR). However, rATG is associated with severe infusion-related side effects. Alemtuzumab is incidentally given to kidney transplant recipients as treatment for AR. In the current study, the outcomes of patients treated with alemtuzumab for AR were compared with that of patients treated with rATG for AR. The patient-, allograft-, and infection-free survival and adverse events of 116 alemtuzumab-treated patients were compared with those of 108 patients treated with rATG for AR. Propensity scores were used to control for differences between the two groups. Patient- and allograft survival of patients treated with either alemtuzumab or rATG were not different [hazard ratio (HR) 1.14, 95%-confidence interval (CI) 0.48-2.69, = 0.77, and HR 0.82, 95%-CI 0.45-1.5, = 0.52, respectively). Infection-free survival after alemtuzumab treatment was superior compared with that of rATG-treated patients (HR 0.41, 95%-CI 0.25-0.68, < 0.002). Infusion-related adverse events occurred less frequently after alemtuzumab treatment. Alemtuzumab therapy may therefore be an alternative therapy for glucocorticoid-resistant, recurrent, or severe acute kidney transplant rejection.
Topics: Adult; Alemtuzumab; Allografts; Antilymphocyte Serum; Female; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Retrospective Studies
PubMed: 32719676
DOI: 10.3389/fimmu.2020.01332