COVID-19 in patients with aggressive MS treated with aHSCT: A multi-center study

Introduction: Onco-hematological patients, specifically those treated with hematopoietic stem cell transplantation (HSCT) [2], are particularly at risk of severe acute respiratory syndrome due to Coronavirus-2 (SARS-CoV-2). Conversely, evidences regarding Coronavirus Disease 2019 (COVID-19) in aggressive multiple sclerosis (MS) treated with autologous HSCT (aHSCT) are not available. At pandemic start, and in the absence of data, European Society for Blood and Marrow transplantation/Autoimmune Disease Working Party (EBMT/ADWP) suggested delaying not life-sparing HSCT. Aim: To describe cases of COVID-19 in a population of aggressive MS treated with aHSCT. Materials and Methods: Data were collected from 4 centers (march-2020 to april-2021). Patients' health-status was periodically monitored by phonecall. Patients transplanted within a 12-month period were asked to maintain a strict home-isolation. Those transplanted from longer than 12 months were asked to keep safe behaviour, as recommended by EBMT/ADWP. Results: We recorded 5 cases out of 70 patients. At COVID-19 time, mean (standard deviation) disease duration (dd) was 12.0 (±4.9) years and median expanded disability status scale (EDSS) was 4.5 (range 3.0-7.5). Mean time from aHSCT was 24.7 (±9.8) months (range 12.9-37.0). All patients presented normal lymphocyte values besides one with grade-two lymphopenia (617.0 cc/ mm

Balancing benefits and risks in treating aggressive MS within COVID-19 pandemic: A single-center experience

Background and aims: Severe acute respiratory syndrome due to Coronavirus 2 (SARS-CoV-2) pandemic forced deferrals on most of autologous hematopoietic stem-cell transplantation (aHSCT), specifically for autoimmune diseases, in line with European Society for Blood and Marrow transplantation/Autoimmune Disease Working Party indications. Though concerns on the possible repercussions of the infection in transplanted autoimmune patients required higher monitoring, the impending activity that characterizes some forms of Multiple Sclerosis (MS) demanded a special evaluation on the benefit-risk balance. We aim to describe our experience in treating MS-patients with aHSCT along SARS-CoV-2-pandemic. Methods: Patients candidated to aHSCT were collegially discussed with our haematological and infectious-diseases expertise. two consecutive SARS-CoV-2 negative swabs, a two-weeks-long home-isolation and a five-days intradepartment observation were required for treatment start. Patients recently transplanted were all asked to keep safe behaviour and periodically monitored for possible Coronavirus Disease 2019 (COVID-19) symptoms;in particular, those treated in the previous 12-month were asked to maintain a strict home-isolation. Results: None of the three patients transplanted during pandemic (July, November and December 2020) developed COVID-19. Of the six transplanted in 2019 and that reached one-year from procedure within the outbreak, One developed pauci-symptomatic COVID-19 at the 13th month, confirmed by SARS-CoV-2 swab;white-bloodcells, lymphocyte (totals, CD4+, CD8+ and CD19+) and gamma-globulins levels were normal. two of the remaining 17 patients transplanted from 2015 developed slight COVID-19 symptoms at 30th and 57th month respectively. Conclusion: Three patients with highly-active MS were treated with aHSCT during pandemic without complications;three minor cases of COVID-19 were recorded in our cohort.

Personalizing ocrelizumab treatment in Multiple Sclerosis: What can we learn from Sars-Cov2 pandemic?

During SARS-CoV-2 pandemic, we adopted a personalized delayed protocol for ocrelizumab infusions in Relapsing Remitting Multiple Sclerosis (RRMS) patients according to the national recommendations. Out of the 83 RRMS patients whose infusion was scheduled between March and December 2020, 56 patients experienced a delay in treatment based on MS severity and SARS-CoV2 infection risk profile. In most cases, the immunophenotype was performed monthly to guide re-infusions. Specifically, B CD19 + cells repopulation rate was monitored. Mean infusion delay was 103,1 [SD 40,6] days, and none of the patients presented relapses or active disease at MRI at the end of the observation period. Treatment naïve status and the interval between immunophenotyping and the last ocrelizumab infusion were predictors of earlier B CD19 + cells repopulation. Two patients contracted SARS-CoV2 with complete recovery. Definitive data about Sars-Cov2 vaccine efficacy in patients treated with ocrelizumab are still lacking. Our findings suggest that a personalized treatment with a delayed infusion schedule does not compromise ocrelizumab short-term efficacy and may help to lengthen the therapeutic window for an effective response to SARS-CoV2 vaccine.

Treatment with ocrelizumab during SARS-CoV2 pandemic: Efficacy and safety outcomes

Background: Sars-Cov2 pandemic led neurologists to modify the therapeutic approach in Multiple Sclerosis (MS) care setting, especially with regard to immunodepleting treatments. Objectives: to describe management and outcome of MS patients (pts) treated with ocrelizumab (OCR) during Sars-Cov2 pandemic in the MS Center of University of Genoa. Methods: we collected data about pts scheduled to undergo OCR infusion from 1st March to 30th June 2020. Pts that previously underwent the first OCR infusion completed the induction cycle. No further OCR cycles during March and April 2020 were performed. Starting from May, we adopted an infusion scheme based on B-cell repopulation, differently applied for Relapsing Remitting (RR) and Progressive (P) pts. RRMS pts performed immunophenotype (IF) and received OCR infusion when B CD19+ cell count overcame the cut-off of 1%. Conversely, for PMS pts OCR infusions were delayed for 3 months. Then, PMS pts underwent OCR infusion based on B CD19+ cell monitoring. For pts with evidence of B CD19+ cells repopulation brain 3T MRI was planned before OCR re-infusion. Results: 77 MS pts were included [45 (58%) RRMS, 32 (41%) PMS;mean age 44.7 (SD: 11.1) years, mean disease duration 21.7 (22.3) years, mean number of previous DMT before OCR: 1.6 (1.6), mean number of previous OCR infusions 3.9 (SD 2.3). 11 (13.1%, 9 RR, 2 PP) of the 49 pts that performed a first IF presented B CD19+ cell repopulation and received OCR re-infusion, with a mean delay from scheduled infusion of 70 (48.9) days. The mean number of previous OCR infusions was 3.0 (1.2) and 3.1 (1.6) for pts with and without evidence of B-cell repopulation respectively. No effect of previous OCR infusions number on the probability to develop B CD19+ cell repopulation at the first IF was detected by ANCOVA analysis, correcting for the delay between the date of scheduled infusion and the date in which the first IF has been performed. Considering the global cohort, 1 pt presented a dubious sensory relapse with no evidence of radiological activity. None of the pts who performed brain MRI before OCR re-infusion showed new T2 or Gd+ enhancing lesions. 3 pts were infected by Sars- Cov2;2 of them needed hospitalization but recovered completely. Conclusions: the management of patients treated with OCR during Sars-Cov2 pandemic with a personalized infusion protocol based on B CD19+ cells repopulation was associated with good results in terms of efficacy and safety outcome.