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ACTRIMS POSTER: AHSCT in MS, the Zurich Experience after 24 Months

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  • ACTRIMS POSTER: AHSCT in MS, the Zurich Experience after 24 Months

    P0295 - Autologous Hematopoietic Stem Cell Transplantation in Multiple Sclerosis (aHSCT-in-MS): The Zurich Experience 24 Months after Approval (ID 1828)

    Speakers
    Authors
    Presentation Number
    P0295
    Presentation Topic
    Disease Modifying Therapies – Risk ManagementBackground
    Autologous hematopoietic stem cell transplantation (aHSCT) is used for highly active relapsing-remitting or progressive forms of multiple sclerosis (MS) since 1995. Based on increasing evidence regarding efficacy and improved safety of aHSCT in MS, the Swiss Federal Office of Public Health (FOPH) granted approval in June 2018 with the requirement that patients participate in a prospective registry study at our institution (“aHSCT-in-MS”) to assess clinical, radiological, laboratory and safety measures for 5 years after transplantation.

    Objectives
    We here report adverse events (AEs) and severe AEs after hematopoietic stem cell mobilization and aHSCT for MS in Zurich, Switzerland.

    Methods
    All data is collected systematically using RedCap. Hematopoietic stem cells are mobilized with 2 days of cyclophosphamide 2g/m2/d and granulocyte-colony stimulating factor. Conditioning high-dose chemotherapy comprises BEAM-ATG, i.e. BCNU, etoposide, cytarabine, melphalan before- and ATG (d+1 and +2: 3.75 mg/kg/d) after stem cell re-transfusion (d0).

    Results
    26 MS patients (13 females, 13 males) with a mean age of 40.8±7.8 years, mean disease duration of 8.9±4.8 years and a mean expanded disease status scale (EDSS) score of 5.0±1.2 have been treated with aHSCT. 10/26 (38.5%) patients had relapsing-remitting MS, 9/26 (34.6%) secondary-progressive MS and 7/26 (26.9%) primary-progressive MS. aHSCT was indicated because 8/26 (30.8%) patients had clinical activity (i.e. relapses), 13/26 (50.0%) had radiological activity (i.e. new or contrast-enhancing CNS lesions) and 16/26 (61.5%) had clinical progression – despite conventional highly effective immunomodulatory therapy. We observed infectious AEs in the majority of patients, i.e. mucositis, pharyngitis and/or enteritis (24/26), upper airway (9/26) and urinary (8/26) infection, symptomatic reactivation of CMV (4/26), HSV (5/26), VZV (2/26) and BKV (3/26). Other AEs included Uhthoff’s phenomenon (14/26), hypotension (3/26), epistaxis and cholecystolithiasis (each 1/26). Severe AEs included 4 cases with neutropenic fever, 2 symptomatic CMV reactivations, each 1 urosepsis, hemorrhagic cystitis, gastroenteritis with ileus, laryngitis, pharyngitis, cervical abscess, pulmonary embolism, gastrointestinal bleeding, manic episode, depressive reaction and emesis. Although a substantial proportion of patients reported improvements of neurological functions and less fatigue, follow-up is too short to comment on long-term outcomes.

    Conclusions
    The safety profile of aHSCT-in-MS is acceptable, but requires vigilant monitoring and optimized antibacterial and antiviral prophylactic care. Regarding the increased risk of CMV reactivation (4/7 CMV-seropositive patients) and herpes zoster (2/26), we decided to establish prophylaxis with the CMV inhibitor letermovir in CMV-seropositive patients and to vaccinate all patients with Shingrix® after transplantation.
    Dave Bexfield
    ActiveMSers
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