Epstein-Barr Virus and Monoclonal Gammopathy of Clinical Significance in Autologous Stem Cell Transplantation for Multiple Sclerosis.

INTRODUCTION: Autologous hematopoietic stem cell transplantation (AHSCT) with anti-thymocyte globulin (ATG) conditioning as treatment of active multiple sclerosis (MS) is rapidly increasing across Europe (EBMT registry data 2017). Clinically significant Epstein-Barr virus reactivation (EBV-R) following AHSCT with ATG for severe autoimmune conditions is an underrecognized complication relative to T-cell deplete transplants performed for hematological diseases. This retrospective study reports EBV-R associated significant clinical sequelae in MS patients undergoing AHSCT with rabbit ATG. METHODS: Retrospective data were analyzed for 36 consecutive MS-AHSCT patients at Kings College Hospital, London. All patients routinely underwent weekly EBV DNA polymerase chain reaction monitoring and serum electrophoresis for monoclonal gammopathy (MG or M-protein). EBV-R with rising Epstein-Barr viral load, M-protein, and associated clinical sequelae were captured from clinical records. RESULTS: All patients had evidence of rising EBV DNA-emia, including 7 who were lost to long-term follow-up, with a number of them developing high EBV viral load and associated lymphoproliferative disorder (LPD). Nearly 72% (n = 18/29) developed de novo MG, some with significant neurological consequences with high M-protein and EBV-R. Six patients required anti-CD20 therapy (rituximab) with complete resolution of EBV related symptoms. Receiver operating characteristics estimated a peak EBV viremia of >500 000 DNA copies/mL correlated with high sensitivity (85.5%) and specificity (82.5%) (area under the curve: 0.87; P = .004) in predicting EBV-R related significant clinical events. CONCLUSION: Symptomatic EBV reactivation increases risk of neurological sequelae and LPD in MS-AHSCT. We recommend regular monitoring for EBV and serum electrophoresis for MG in MS patients in the first 3 months post-AHSCT.

Detecting acute distress and risk of future psychological morbidity in critically ill patients: validation of the intensive care psychological assessment tool.

INTRODUCTION: The psychological impact of critical illness on a patient can be severe, and frequently results in acute distress as well as psychological morbidity after leaving hospital. A UK guideline states that patients should be assessed in critical care units, both for acute distress and risk of future psychological morbidity; but no suitable method for carrying out this assessment exists. The Intensive care psychological assessment tool (IPAT) was developed as a simple, quick screening tool to be used routinely to detect acute distress, and the risk of future psychological morbidity, in critical care units. METHODS: A validation study of IPAT was conducted in the critical care unit of a London hospital. Once un-sedated, orientated and alert, critical care patients were assessed with the IPAT and validated tools for distress, to determine the IPAT's concurrent validity. Fifty six patients took IPAT again to establish test-retest reliability. Finally, patients completed posttraumatic stress disorder (PTSD), depression and anxiety questionnaires at three months, to determine predictive validity of the IPAT. RESULTS: One hundred and sixty six patients completed the IPAT, and 106 completed follow-up questionnaires at 3 months. Scale analysis showed IPAT was a reliable 10-item measure of critical care-related psychological distress. Test-retest reliability was good (r =0.8). There was good concurrent validity with measures of anxiety and depression (r =0.7, P <0.01; r =0.6, P <0.01). With a cut-point of ≥7, the IPAT had 82% sensitivity and 65% specificity to detect concurrent anxiety; and 80% sensitivity and 66% specificity to detect concurrent low mood (area under the curve (AUC) =0.8 for both). Predictive validity for psychological morbidity was good (r =0.4, P <0.01; r =0.64, P <0.01 for PTSD with days 1 and 2 data). The IPAT had 69% specificity and 57% sensitivity to predict future psychological morbidity (AUC =0.7). CONCLUSIONS: The IPAT was found to have good reliability and validity. Sensitivity and specificity analysis suggest the IPAT could provide a way of allowing staff to assess psychological distress among critical care patients after further replication and validation. Further work is also needed to determine its utility in predicting future psychological morbidity.

Autologous Hematopoietic Stem Cell Transplantation in Active Multiple Sclerosis: A Real-world Case Series.

OBJECTIVE: To examine outcomes in people with multiple sclerosis (PwMS) treated with autologous hematopoietic stem cell transplantation (AHSCT) in a real-world setting. METHODS: This was a retrospective cohort study of PwMS treated with AHSCT at 2 centers in London, UK, consecutively between 2012 and 2019 who had ≥6 months of follow-up or died at any time. Primary outcomes were survival free of multiple sclerosis (MS) relapses, MRI new lesions, and worsening of Expanded Disability Status Scale (EDSS) score. Adverse events rates were also examined. RESULTS: The cohort includes 120 PwMS; 52% had progressive MS (primary or secondary) and 48% had relapsing-remitting MS. At baseline, the median EDSS score was 6.0; 90% of the evaluable cases showed MRI activity in the 12 months preceding AHSCT. Median follow-up after AHSCT was 21 months (range 6-85 months). MS relapse-free survival was 93% at 2 years and 87% at 4 years after AHSCT. No new MRI lesions were detected in 90% of participants at 2 years and in 85% at 4 years. EDSS score progression-free survival (PFS) was 75% at 2 years and 65% at 4 years. Epstein-Barr virus reactivation and monoclonal paraproteinemia were associated with worse PFS. There were 3 transplantation-related deaths within 100 days (2.5%), all after fluid overload and cardiac or respiratory failure. CONCLUSIONS: Efficacy outcomes of AHSCT in this real-world cohort are similar to those reported in more stringently selected clinical trial populations, although the risks may be higher. CLASSIFICATION OF EVIDENCE: This study is rated Class IV because of the uncontrolled, open-label design.

Pulmonary Sarcoidosis in a patient with Multiple Sclerosis on daclizumab monotherapy.

As new immunomodulatory therapies continue to be licensed for use in Multiple Sclerosis, it is important to remain vigilant for new, unexpected associations relating to these medications. We highlight this by reporting on a case of a 45-year-old man who developed systemic, non-specific symptoms following long term use of daclizumab and was subsequently diagnosed with sarcoidosis. We go on to briefly discuss the action of daclizumab, in particular the effect it has on CD56bright natural killer cells, a cell type that has been investigated in relation to sarcoidosis.