Alemtuzumab (ALZ), a monoclonal antibody used to treat relapsing-remitting multiple sclerosis (RRMS), is associated with a high risk ofautoimmune thyroid disorders, particularly Graves' disease (GD). Managing ALZ-induced GD during pregnancy presents unique challenges due to fluctuating thyroid function and potential fetal risks. However, the literature on this specific condition remains limited, with only a few case reports and commentaries available. The case-history of a 36-year-old woman diagnosed with GD at 11 weeks of gestation, 16 months after receiving her last ALZ dose is described. She was treated with methimazole (MMI), with multiple dose adjustments throughout pregnancy to maintain euthyroidism. Despite persistently elevated TSH receptor antibodies levels, fetal development occurred normally, and she delivered a healthy newborn. The infant experienced transient neonatal hyperthyroidism with spontaneous recovery without treatment. In the postpartum period, both mother and child were closely monitored. As the infant's condition stabilized, the mother's MMI dose was gradually increased. At seven months postpartum, she remains euthyroid on 15 mg/day of MMI, with no clinical/radiological signs of multiple sclerosis relapse. The present case adds to the limited literature on ALZ-induced GD in pregnancy, providing further insight into the variability of disease onset, progression, and neonatal outcomes. It underscores the importance of close monitoring and a multidisciplinary approach to ensure optimal maternal and fetal health.

Background and ObjectivesUnderstanding the immunologic changes induced by immune reconstitution therapies (IRTs) is key to optimizing multiple sclerosis (MS) treatment. We evaluate lymphocyte dynamics and their association with secondary autoimmune disease (SAD) and its recurrence after treatment with alemtuzumab (ALZ), autologous hematopoietic stem cell transplantation (AHSCT), and cladribine tablets (CladT).MethodsPeople with MS (pwMS) initiating treatment with ALZ, AHSCT, and CladT were included in this cohort study. Blood samples were collected at baseline (BL) and at months (M) 6, 12, and 24 for flow cytometry analysis of lymphocyte subpopulation.ResultsA total of 130 pwMS (ALZ: n = 51; AHSCT: n = 20; CladT: n = 59) were included, with a mean (SD) age of 35.5 (±8.2) years. The median (IQR) Expanded Disability Status Scale (EDSS) score was 1.5 (1.0–2.5) at BL. The median follow-up duration was 4.7 (ALZ: 5.0; AHSCT: 4.2; CladT: 3.7) years. During follow-up, 29.2% (38/130; ALZ n = 29; AHSCT n = 3; CladT n = 6) received a SAD diagnosis and 43.1% (56/130; ALZ n = 15; AHSCT n = 13; CladT n = 28) showed no disease activity. The SAD cohort (n = 38) showed lower median BL ratios of CD4+ T-cell recent thymic emigrant (Trte):CD4 (0.26 [0.12–0.34], p = 0.04) and CD4+ Trte:CD8+ terminally differentiated effector memory (Temra) (1.73 [0.76–4.39], p = 0.02) compared with the non-SAD cohort (CD4+ Trte:CD4 = 0.31 [0.23–0.42]; CD4+ Trte:CD8+ Temra = 3.61 [1.47–7.24]). During follow-up, the SAD cohort exhibited a greater relative increase in CD4+ Trte:CD4, CD4+ Trte:CD8+ Temra, and CD4+ T regulatory cell (Treg):CD8+ Temra ratios at M12 and M24, compared with BL, relative to the non-SAD group. The difference at M24 was most pronounced for the CD4+ Trte:CD8+ Temra ratio (SAD: +100% vs non-SAD: −23%, p < 0.001), with this difference being confirmed in the ALZ cohort (SAD: +123% vs non-SAD: −21%, p = 0.03), but not in the CladT cohort (SAD: −62% vs non-SAD: −38%, p = 0.39). In a multivariable Cox analysis, BL CD8+ T-cell count (aHR 0.34, 95% CI 0.15–0.80, p = 0.01) was associated with a reduced hazard of evidence of disease activity.DiscussionA low BL CD4+ Trte:CD8+ Temra ratio, accompanied by a sharp relative increase during follow-up, was associated with SAD development. While no definitive associations were found between BL lymphocyte subpopulations and disease activity, a lower CD8+ T-cell count may suggest an increased risk.

IntroductionThe measurement of brain atrophy in patients with relapsing–remitting multiple sclerosis (RRMS) may be a marker of the disease activity. However, currently this method is not widely used in clinical practice. In the presented study, the relationship between lesions (T2) in magnetic resonance imaging (MRI), including contrast-enhancing (Gd+), clinical relapses and no evidence of disease activity (NEDA-3) with volumetric changes was investigated.MethodsClinical and MRI data from RRMS patients treated with cladribine tablets (CLAD) and alemtuzumab (ALEM) were retrospectively analyzed at 4 time points (pretreatment and 3 years of follow-up). Volumetric data were obtained using the FreeSurfer. Annual volumetric changes and new T2/Gd + lesions were pooled together to assess short-term relationships, baseline T2/Gd + lesions were correlated with 3-year volume changes and years with NEDA-3 and without NEDA-3 were compared.ResultsThe study included 33 patients treated with CLAD and 19 patients treated with ALEM. In the year-to-year analysis (nCLAD = 59, nALEM = 36) within the CLAD group, new T2 lesions were significantly associated with a decrease in thalamic (p = 0.02), cerebellum (p = 0.05) and deep grey matter (p = 0.05) volume. When analyzing the correlation between baseline T2 lesions and overall 3-year volume changes (NCLAD = 9, NALEM = 7), in the CLAD group, strong associations were found with whole brain (p = 0.001, ꞵ = −0.89), cerebellum (p = 0.002, ꞵ = −0.20), cerebellar cortex (p = 0.003, ꞵ = −0.19) and DGM (p = 0.015, ꞵ = −0.04) atrophy, as well as with lateral ventricular volume increase (p = 0.00001, ꞵ = 0.1). A similar situation occurred when only the first year of treatment was analyzed (NCLAD = 29, NALEM = 13). It was not observed in the ALEM group. Interestingly, no correlation was noted between Gd + lesions and volumetric changes. Remarkably, no statistically significant differences between years with and without relapses were observed. However, years without NEDA-3 (n = 31) were characterized by greater atrophy in white matter (p = 0.04), thalamus (p = 0.02), and putamen (p = 0.04).ConclusionThe results of the presented study suggested an association of increased brain atrophy with radiological activity rather than with relapsing disease activity. However, further studies with larger numbers of patients are needed to verify these associations more precisely.

IntroductionBrain atrophy may be a promising marker of relapsing-remitting multiple sclerosis (RRMS) progression, yet it remains underutilized in clinical practice. This exploratory study evaluated correlations between disability—as measured by the Expanded Disability Status Scale (EDSS) and progression independent of relapse activity (PIRA)—and volumetric changes in RRMS patients treated with cladribine tablets (CLAD) or alemtuzumab (ALEM).MethodsClinical and magnetic resonance imaging (MRI) data from patients with RRMS were retrospectively analyzed at four time points: pretreatment and annually over three years of follow-up. Volumetric measurements were obtained using FreeSurfer. Annual volumetric and EDSS changes were pooled together to assess short-term associations and patient-wise longitudinal analyses were performed.Results33 patients treated with CLAD and 19 patients treated with ALEM were included. Analyzing year-to-year correlations, a significant positive correlation was found between EDSS and amygdala volume changes (p = 0.00009, η²=0,15657). It was also observed for the pallidum (p=0,02605, η²=0,05384). On the contrary, a negative correlation between thalamic volume changes and EDSS in CLAD group was noted (p=0,04551, η²=0,07203).When comparing annual percentage volume changes across three groups—years with EDSS progression (n = 10), regression (n = 11), and no changes (n = 74)—significant differences were reported in amygdala (p=0,00640; 1.98%, -4%, -0.8%), thalamus (p = 0,04390; -0.54%, 2.98%, 0.1%) and pallidum (p = 0,02904; 1.98%, -6.96%, -0.23%). Finally, among the 10 patients with EDSS progression, an increase in amygdala volume was observed in 3 patients with PIRA, whereas it was not seen in the 7 patients whose EDSS progression was associated with relapsing activity (p = 0.0188; 4.60% vs. 0.004%).ConclusionOver three years of follow-up in RRMS patients, EDSS progression was positively associated with increases in amygdala—and, to a lesser extent, pallidum—volumes, while worsening disability correlated with thalamic atrophy. Notably, amygdala enlargement was exclusive to patients with PIRA versus relapse-associated worsening, highlighting its potential as a volumetric biomarker of disease progression. However it was exploratory, hypothesis-generating observation and further studies are warranted to validate these findings and elucidate the underlying mechanisms.

Comparative analysis of five-year clinical outcomes of autologous hematopoietic stem cell transplantation and alemtuzumab in multiple sclerosis patients.

During the COVID-19 pandemic our center adjusted the standard induction therapy for normal immunological risk simultaneous pancreas-kidney (SPK) transplantations from T-cell depletion by alemtuzumab (ALEM) to IL-2 receptor blocking by basiliximab (IL2R). Here, we analyze the impact of this change on 1 year post-transplantation outcomes. Thirty-six adult patients who underwent SPK transplantation between June 2015 and June 2023 were included, of whom 21 before February 2020 (ALEM) and 15 after February 2020 (IL2R). Patients were stratified into two groups based on the induction therapy received. One death occurred during the follow up period. A total of three pancreas and two kidney grafts were lost. No differences between kidney and pancreas graft function or rejection rates were observed. Patients receiving IL2R induction had significantly lower 30 day postoperative complication rates (34 vs. 46%, p = 0.03) and experienced fewer bacterial infections (< 6 months: 47 vs. 81%, p = 0.03). Additionally, lower rates of viral (including CMV) and fungal infections were observed. IL2R patients also had a significantly shorter hospital admission durations (14 vs. 30 days, p < 0.001). In conclusion, IL2R induction in SPK recipients was associated with similar short-term graft function and potentially improved outcomes compared to ALEM, warranting cautious interpretation due to sample size.

Disease-modifying therapies (DMTs) have significantly improved the management of multiple sclerosis (MS), but their potential nervous system adverse events (AEs) remain a critical concern. This study aims to evaluate the risk of nervous system AEs associated with 11 DMTs using the FDA Adverse Event Reporting System (FAERS) database, following the READUS-PV guidelines. We performed a disproportionality analysis on FAERS data from Q1 2004 to Q3 2024, focusing on nervous system AEs related to DMTs, such as Alemtuzumab (AL), Ofatumumab (OF), Ocrelizumab (OC), and Fingolimod (FI). Using disproportionality analysis and Bayesian methods, we identified signals of these AEs. We also conducted subgroup analyses across age, gender, weight, geographic regions, and outcomes to assess AE distribution. In addition, a sensitivity analysis was done to evaluate the consistency of the association between DMTs and nervous system AEs across severities. The time to onset and clinical characteristics of AEs were examined as well. Among 245,469 nervous system AE reports, Siponimod (SI), Natalizumab (NA), FI, and Teriflunomide (TE) exhibited the highest signal values (ROR > 3.0), with SI showing the strongest association [ROR = 3.44, 95% CI (3.34-3.55)]. Females accounted for 76.0% of nervous system AEs, and severe AEs such as central nervous system lesions (mortality rate: 0.97%) and cognitive disorders (mortality rate: 0.94%) were detected. The median time to onset of AEs varied significantly across DMTs, ranging from 14days for AL to 816days for Interferon Beta-1a (IN). Subgroup analyses highlighted variations in AE reporting across different demographics and geographic regions. The sensitivity analysis further confirmed the robustness of our findings, indicating consistent associations between DMTs and severe nervous system AEs. This study highlights significant differences in the nervous system AEs profiles of DMTs, with SI, NA, FI, and TE showing higher risks of nervous system AEs. These findings underscore the importance of vigilant monitoring and personalized treatment strategies to mitigate nervous system risks in MS patients. Further research is needed to confirm these associations and investigate the mechanisms that underlie them.

ObjectiveTo compare clinical and radiological outcomes among relapsing multiple sclerosis patients treated with autologous hematopoietic stem cell transplantation (AHSCT), alemtuzumab (ATZ), and ocrelizumab (OCR).MethodsFrom a London (UK) hospital‐based observational cohort, modeled data were obtained from 621 relapsing–remitting multiple sclerosis patients, who were treated with AHSCT (n = 103), ATZ (n = 204), and OCR (n = 314), and were followed up for 43, 43, and 32 median months, respectively. The annualized relapse rate, new magnetic resonance imaging (MRI) lesions, and disability progression on Expanded Disability Status Scale were assessed.ResultsAHSCT showed superior efficacy compared with ATZ and OCR. After 5‐year follow up, the mean annualized relapse rate (0.026 vs 0.087; p < 0.001), the risk of relapses (HR 0.29, 95% CI 0.13–0.63; p = 0.002), and of MRI activity (HR 0.33, 95% CI 0.15–0.72; p = 0.006) were significantly lower in AHSCT versus ATZ group. Compared with OCR, after 3‐year follow‐up AHSCT showed a significantly lower annualized relapse rate (0.028 vs 0.073; p = 0.02) and a trend to reduced risk of relapse (HR 0.45, 95% CI 0.18–1.14; p = 0.09), but similar low rates (6%) of new MRI activity (HR 0.86, 95% CI 0.28–2.67; p = 0.80). In addition, there was a similar risk of Expanded Disability Status Scale progression in AHSCT, and both ATZ (HR 1.19, 95% CI 0.71–2.00; p = 0.50) and OCR (HR 1.08, 95% CI 0.57–2.04; p = 0.82) groups.InterpretationAHSCT was followed by greater prevention of relapses compared with ATZ and OCR, and suppressed more profoundly MRI activity than ATZ, but similarly to OCR, albeit with shorter follow up. The risk of accumulating disability was similar among the treated groups. Studies with larger sample sizes and longer follow up may enable confirmation of these findings or detection of any additional differential effects. ANN NEUROL 2025;98:294–307

Immune reconstitution therapies (IRT) are highly effective therapies for multiple sclerosis (MS). Among IRT, we can distinguish partially selective therapies such as cladribine in tablets (CLAD) and non-selective therapies, which include alemtuzumab (ALEM). Today, it is known that these therapies are effective in controlling the relapse activity of the disease and the progression of clinical disability, which has been proven both in clinical trials and in real world evidence (RWE). However, there is a lack of data assessing the effect of IRT on the neurodegenerative process, which is intensified in patients with MS. The aim of the study was to assess the effect of IRT treatment on the degree and pattern of brain atrophy in patients with MS during 3 years of observation. Patients with relapsing-remitting MS (RRMS) treated with CLAD and ALEM were retrospectively recruited for the study. Demographic, clinical, and magnetic resonance imaging (MRI) data were collected at 4 time points: before the treatment and one, two, and three years after the treatment. MRI examinations were analyzed volumetrically using Freesurfer software. Global and regional changes in atrophy were assessed by calculating percentage changes in volume between time points. Results of drug groups were compared with each other. After 3 years of follow-up, statistically significant differences between groups were observed in hippocampus [p < 0.01] and amygdala volume changes [p < 0.01]. Ventral diencephalon atrophy was noted in both groups. On the other hand, in both groups, no significant atrophy of white and grey matter was noted. In addition, an increase in the thalamus volume was observed. In the studied groups, IRT therapies were shown to slow down the atrophy process in MS patients to a similar extent. These therapies may play a neuroprotective role by increasing the volume of the thalamus and hippocampus. The study was limited by the small number of both groups. Therefore, further studies are needed to fully assess the effect of reconstitution therapies on neurodegenerative processes in patients with RRMS.

Immunosuppressive therapy using horse antithymocyte globulin (ATG; h-ATG) combined with cyclosporine (CsA) and eltrombopag is the standard care for aplastic anemia (AA) in patients without a suitable matched donor. However, in many countries, h-ATG use has been discontinued, leaving rabbit ATG (r-ATG), which has a lower response rates and poorer survival, as the only alternative. In previous studies, alemtuzumab (ALZ), a humanized monoclonal antibody targeting CD52, combined with CsA, resulted in an adequate overall response rate (ORR) in patients with AA. This study describes a multicenter, international retrospective analysis of ALZ for treating AA.We analyzed a series of patients who received subcutaneous ALZ for AA in 4 centers in Brazil and the United Kingdom from March 2009 to January 2024. We analyzed 64 ALZ treatments in 61 adult patients with AA, 76% with severe AA (SAA) or very SAA. The ORR was 59.4% at 12months (complete, 21.9%; partial, 37.5%). Cumulative incidence (CI) of response was 54.7% at 6months and 59.4% at 12months. Younger patients (age <65 years) had higher CI of response (67% vs 31%; P=.03), as did patients treated with a total dose of 103mg (70% vs 38%; P=.02). Overall survival was 86% at 1 year, 78% at 2 years, and 70% at 4 years, significantly higher in responders (90% vs 44%; P< .0001). Adverse events were of low grade, and infectious events were infrequent. Subcutaneous ALZ is a feasible, effective, and safe alternative to r-ATG for patients with AA requiring immunosuppressive treatment when h-ATG access is limited.

Pediatric-Onset Multiple Sclerosis (POMS) is characterized by both white and grey matter inflammation, as well as by a higher risk of long-term physical and cognitive disability. The peculiar immunopathogenic mechanisms of POMS suggests that the use of induction therapies, including alemtuzumab (ALTZ), might be a promising approach, at least for postpuberal (> 11 yo) POMS. Although no data on the use of induction therapies in POMS are available from clinical trials currently, case series or case reports on the effect of alemtuzumab (ALTZ) have been recently published. In this review we have briefly revised the immunopathogenic features of POMS, as well as on how ALTZ might impact on them, reporting its efficacy observed in different POMS cohorts.

The effect of alemtuzumab on neurodegeneration in relapsing-remitting multiple sclerosis: A five-year prospective mono-center study

Background: Uncertainty about disproportionate impact on health care budgets limits implementation of early highly effective treatment (EHT) in multiple sclerosis (MS). Objective: To estimate cost-effectiveness of escalation versus EHT disease-modifying treatment (DMT) sequences. Methods: Using a health-economic approach, we analysed health benefits (relapse rate reduction, disability prevention), direct/indirect DMT and societal costs of escalation versus EHT DMT sequences. In scenario analyses, we allowed (1) earlier use of alemtuzumab (ALE) and (2) a single retreatment with cladribine (CLA). Results: In our model, we showed that the ratio between costs and quality-adjusted life years (QALYs) for the most cost-effective EHT and escalation sequence results into a similar net health benefit with higher costs and also higher QALYs associated with an EHT versus escalation strategy. Earlier use of ALE is more cost-effective than in later lines, even when aggravating the impact of its side-effects tenfold. Retreatment with CLA was more cost-effective in both escalation and EHT sequences. Conclusions: Certain EHT sequences are equally cost-effective to escalation sequences and are likely to result in more health at uncertain additional costs. The favourable cost–benefit ratio of CLA and ALE suggests that a wider application of affordable highly effective therapies could promote the cost-effectiveness both EHT and escalation approaches.

Background/ObjectiveObservational real‐world study to analyze the clinical effects of alemtuzumab (ALEM) and subsequent disease‐modifying therapy (DMT) usage in multiple sclerosis (MS).MethodsData retrieved from the Austrian MS treatment registry (AMSTR) included baseline (BL) characteristics (at ALEM start), annualized relapse rate (ARR), 6‐month confirmed progression independent of relapse activity (PIRA; ≥ 0.5‐point Expanded Disability Status Scale (EDSS) score increase), 6‐month confirmed disability improvement (CDI; ≥ 0.5‐point EDSS decrease), and safety outcomes until initiation of a subsequent DMT. The EDSS was re‐baselined at 30 days from ALEM start (BL EDSS).ResultsEighty‐seven ALEM‐treated patients (median age: 32 years, 72% female, 14% treatment‐naïve) were followed for a median of 55 (interquartile range 31–68) months. We found significant reductions in the ARR from 1.16 before ALEM to 0.15 throughout Years 1–9 (p < 0.001). Subsequent DMTs were initiated in 19 patients (22%, 74% anti‐CD20 monoclonal antibodies). At Year 5 (n = 53), more patients achieved CDI (58%, 95% confidence interval (CI) 45%–71%) than had experienced PIRA (14%, CI 7.5%–24%), and 58% remained relapse‐free. Shorter MS duration (p < 0.001, hazard ratio (HR) 0.86 (CI 0.80–0.93)) and no previous high‐efficacy treatment (p < 0.001, HR 5.16 (CI 2.66–10.0)) were the best predictors of CDI, while PIRA was associated with a higher number of previous DMTs (p = 0.04, HR 3.06, CI 1.05–8.89). We found no new safety signals.InterpretationALEM had long‐lasting beneficial effects on the ARR and disability improvement, especially when initiated early in the course of the disease. Only a subset of patients received subsequent DMTs.

Early recovery of natural killer cells post T-cell depleted allogeneic stem cell transplantation using alemtuzumab “in the bag”

Pivotal studies have reported a significant proportion of patients achieving no evidence of disease activity (NEDA) after 2 cycles of treatment with alemtuzumab (ATZ), that can be maintained for several years. Long-term real-world evidence regarding ATZ as well as subsequent treatment trajectories is still scarce. To analyze the effectiveness and safety of ATZ-treated patients in a tertiary care Belgian center. A retrospective cohort study including 32 patients treated with ATZ between 2015 and 2021 was performed. 32 patients received 2 ATZ courses with a mean follow-up (FU) duration of 5.6years (range: 2.25-8.2). 21.75% patients were treatment naïve. 40.5% were previously treated with natalizumab or fingolimod. NEDA-3 was achieved in 61.3-85% of patients, with failure mostly attributed to recurrence of radiological disease activity. During FU, annualized relapse rates remained very low (0.06-0.14), disability improvement occurred in up to 40.5%, whereas disability worsening occurred in up to 13.5%. Retreatment risk was associated with younger age (< 45years old, Odds Ratio 8.0, p = 0.02) and a higher number of previous DMTs (Hazard ratio 2.7, 95%CI 1.3-7.4, p = 0.02). Safety in our cohort was consistent with the known profile of ATZ. At the end of FU, 65.6% patients remained untreated after 2 or 3 courses of ATZ, while the remaining switched to anti-CD20 therapy or cladribine. ATZ is a high efficacy therapy for active MS, providing long-term remission in a significant proportion of patients. Retreatment was more frequent in younger patients or patients having failed a higher number of previous DMTs.

ObjectivesTo compare the effectiveness of early intensive treatment (EIT) versus escalation treatment (ESC) in a nationwide observational cohort of almost 1000 people with relapsing–remitting multiple sclerosis (RRMS).Materials and methodsThe EIT cohort started with alemtuzumab (AZM), cladribine (CLAD), fingolimod (FTY), natalizumab (NTZ), ocrelizumab (OCR), or ozanimod (OZA); whereas, the ESC cohort was escalated from dimethylfumarate (DMF) or teriflunomide (TERI) to AZM, CLAD, FTY, NTZ, OCR, or OZA within the Austrian MS Treatment Registry. Patients had to stay on therapy for at least 3 months and up to 16 years. The EIT cohort included 743 and the ESC cohort 227 RRMS patients. We used multinomial propensity scores for inverse probability weighting in generalized linear (GLM) and Cox proportional hazards models to correct for the bias of this non-randomized registry study.ResultsEstimated mean annualized relapse rates (ARR) were 0.09 for EIT and 0.4 for ESC patients. The incidence rate ratio (IRR) in the GLM model for relapses showed a decreased relapse probability of 78% for the EIT versus ESC cohort [IRR = 0.22, 95% CI (0.16–0.30), p < 0.001]. Analyzing the time to the first relapse by Cox regression, a hazard ratio (HR) of 0.17 [95% CI (0.13–0.22), p < 0.001] revealed a decreased risk of 83% for the EIT group. Regarding sustained Expanded Disability Status Scale (EDSS) progression for 12 weeks, a HR of 0.55 [95% CI (0.40–0.76), p < 0.001] showed a decreased probability of 45% for the EIT cohort.ConclusionsESC treatment after DMF and TERI revealed a higher relapse and EDSS progression probability compared to EIT in Austrian RRMS patients. Therefore, an early intensive treatment should be started in patients with an active or highly active disease course.

Abstract IntroductionIn kidney transplant recipients (KTRs), steroid‐free maintenance regimens are used to minimize the negative impact of steroid use. Studies comparing alemtuzumab (ALZ) and anti‐thymocyte globulin (ATG) with rapid steroid withdrawal are limited. The aim of this study was to assess a composite outcome of incidence of de novo donor specific antibodies (dnDSAs), biopsy proven rejection (BPAR), graft failure, or death in KTRs receiving ALZ or ATG with a steroid‐free maintenance regimen.MethodsA single‐center, retrospective cohort study was conducted in adult KTRs who underwent rapid steroid withdrawal. There were two cohorts, KTRs who received induction with ALZ compared to ATG. The primary composite outcome was incidence of dnDSAs, BPAR, graft failure, or death. Secondary outcomes included renal function, cytomegalovirus (CMV) and BK viremia, and leukopenia.ResultsTwo hundred twenty‐five KTRs were included where 146 received ALZ and 79 received ATG. The Cox proportional hazard of the primary composite outcome in the ALZ compared to ATG group was not significant (unadjusted model HR 1.37, 95% CI .74–2.55). Individual incidences of composite outcome were similar. There was a difference in estimated glomerular filtration rate at 12 months post‐transplant (55.7 vs. 62.3 mL/min/1.73m2, p = .03) and leukopenia at 3 months (3.7 vs. 4.2 × 109/L, p = .03). Other secondary outcomes were similar.ConclusionsThere was no difference in composite outcome for dnDSAs, BPAR, graft failure, and death.

Alemtuzumab (ALEM) is a humanised monoclonal antibody that depletes circulating lymphocytes by selectively targeting CD52, which is expressed in high levels on T- and B-lymphocytes. This depletion is followed by lymphocyte repopulation and a cytokine expression shift towards a lesser inflammatory profile, both of which may contribute to prolonged efficacy. National recommendations for enrolling and treating multiple sclerosis (MS) patients with ALEM have been established. However, there are no recommendations in place for the treatment of MS reactivation after the ALEM treatment. To evaluate the effectiveness and safety of the use of ALEM and to analyse subsequent disease-modifying treatments (DMTs). A multidimensional prediction model was developed to make a patient-specific prognosis regarding the response to ALEM. A multicentre, prospective, non-controlled, non-interventional, observational cohort study. Relapsing multiple sclerosis patients (RMSp) who received ⩾1 dose of ALEM were enrolled. In each treatment year, the following baseline and prospective data were collected: age, MS history, number, type and duration of previous disease-modifying treatment (PDMT), relapse rate (REL), expanded disability status scale (EDSS), magnetic resonance imaging and serious adverse events (AE). In cases of reactivation of MS, all data about the subsequent DMT were collected. A total of 142 RMSp from 10 MS Slovak Centres fulfilled the inclusion criteria. The average age was 35 years (standard error 8.56). The overall average EDSS was 3.87 (1.46) when ALEM was started. The average duration of PDMT was 6.0 (4.04) years, and the median number of PDMTs was 3 (0-5), while the patients were mostly treated with 2 or 3 DMTs (>65.00%). Post-ALEM treatment was needed in 39 cases (27.46%). The most frequent post-ALEM treatment indicated was ocrelizumab, followed by natalizumab (NAT), siponimod and cladribine. The ocrelizumab and NAT treatment bring little benefit to patients. Siponimod showed less EDSS increase in contrast to ocrelizumab and NAT. Another repopulation therapy, cladribine, may also be an effective option. Statistically significant predictors for the expected EDSS are age (p-value <0.0001), number of ALEM cycles (0.0066), high number of PDMT (0.0459) and the occurrence of relapses (<0.0001). There was no statistically significant effect on the patient's gender (0.6038), duration of disease-modifying treatment before alemtuzumab (0.4466), or the occurrence of AE (0.6668). The study confirms the positive effect of ALEM on clinical and radiological outcomes. We need more data from long-term sequencing studies.

Regimen Intensity and Age Affect Transplant-Related Outcomes after Matched Related Donor Hematopoietic Cell Transplantation for Sickle Cell Disease: A STAR Registry Study