ABSTRACT
Introduction: The COVID-19 pandemic profoundly impacts education in hematology residency programs due to contact restrictions imposed by national and local authorities. Nevertheless, education with face-to-face trainings is essential, particularly in teaching cytomorphology of bone marrow, peripheral blood and body fluids. The development of high resolution digital microscopy (DM) allows digitalization of cytomorphological specimens. In the COVID-19 pandemic we have established several teaching formats using DM. This work was supported by DKH and DGHO. Methods: Throughout 2020, more than 150 slides from peripheral blood films, bone marrow smears, CSF and pleural, pericardiac and peritoneal effusions were scanned and digitalized. We used a high-speed camera combined with manual scanning software. For DM courses (DMC) we used commercially available software (ZoomTM). Evaluation of in-house teaching was performed by a Likert scale survey to assess acceptance, technical problems and motivation. Results: We established several teaching formats, including weekly in-house cytology rounds for residents and the DMC series 'Hematology for beginners', a 90-minutes webinar on certain topics, including myeloma, acute leukemia, anemia and myelodysplastic syndromes that took place four times during the last year. Further DMC are planned in 2021. There was a growing number of participants with a maximum of up to 139 participants. The evaluation showed that DMC were well accepted by in-house residents and participants of different institutions and also by faculty members. Technical performance was feasible with only very few technical problems due to poor bandwidth of internet connection. Conclusion: DMC in cytomorphology are feasible. The limitations of DM include availability of sufficient bandwidth, quality of the blood or bone marrow smears, and inability of participants to physically handle the microscope. Nonetheless, DMC may help to bridge the educational gap for cytomorphology teaching during these unprecedented circumstances in the COVID-19 pandemic. It supports preserving the health and live of our patients, colleagues and trainees by distanced learning and can be performed both for smaller and larger audience. These advantages of DM may prevail after the COVID-19 pandemic, further support daily education and have the potential to shape the future of morphology teaching.
ABSTRACT
Introduction: Up to now,reliable results regarding the efficacy of anti-SARS-CoV-2 vaccines in patients with multiple myeloma (MM), especially under current myeloma-directed therapy, are scarcely available. Here, we report an analysis describing the level of post-vaccination antibody titers after the 1 stand 2 ndanti-SARS-CoV-2 vaccination depending on therapy, remission status, and B- and T-cell numbers in patients with MM and related plasma cell neoplasia. Methods: This observational single-center study included patients aged ≥18 years with diagnoses of MM, monoclonal gammopathies of clinical significance (MGCS), or systemic light-chain amyloidosis (AL) who were eligible for Anti-SARS-CoV-2 vaccination according to the International Myeloma Society recommendations. Patients with prior COVID-19 infections were excluded. Samples were analyzed for the presence of SARS-CoV-2 specific antibodies using the quantitative anti-spike IgG (SARS-CoV-2 spike RBD IgG, cut off ≥ 0.8 BAU/ml) according to manufacturer's recommendations. SARS-CoV-2 spike protein antibody titer (SP-AbT) were evaluated after at least 7 days after the 1 stand 2 ndvaccination, respectively. This study was performed between January 1 - July 15, 2021, at the University Medical Center Hamburg-Eppendorf, Germany, as part of the COVIDOUT trial (NCT04779346). All patients provided written informed consent. Aims of this study were to evaluate a possible correlation between SP-AbT and CD19+ B lymphocyte count, as well as to identify other factors impacting vaccination response. Results: 82 patients who received SARS-CoV-2 vaccines (including 67 patients with mRNA-, 8 with vector-based vaccines and 4 heterologous vaccinations) were included. 74 patients had diagnosis of MM, 4 of MGCS/smoldering MM and 4 of AL. Median age was 68 years (range 35-85) and 49 patients were male. In total, 37 patients (45.1%) received anti-CD38- and 2 (2.4%) anti-SLAMF7-targeting therapies at the time of vaccination, 52 (63.4%) patients received immunomodulatory drug (IMID)-based treatments and 13 patients (15.9%) were under active surveillance. 59% of patients had newly diagnosed and 41% refractory or relapsed disease. In total, 75.6% of all patients were in deep remissions (very good partial remission or better). Assessment of anti-SARS-CoV-2 antibody titers took place in median 23 days (range [r] 8-63 days) after the 1 stand 21 days (r: 6-53) after the 2 ndvaccination. A positive SARS-CoV-2 SP-AbT was detected in 31.9% of assessable patients with an overall median SP-AbT of 0 BAU/ml (r: 0-10328, mean 202.36) after the 1 stvaccination and increased up to 88.9% (median SP-AbT of 216.87 BAU/ml, r: 0-25720, mean 2139.29) after 2 ndvaccination. Of the patients not showing positive SP-AbT after the 1 stvaccination, 80.9% became positive after 2 ndvaccination, while 19.1 % remained negative. Median SP-AbT titer was significantly lower compared to patients who became positive already after 1 stvaccination (51.04 vs. 2191.87 BAU/ml, p<0.0001). Regarding immune status, a CD19+ B cell count of median 33.5/µl (r: 1-696/µl) was seen in the overall patient cohort;in patients with negative SP-AbT, median CD19+ B cell numbers were significantly lower compared to patients with positive titers (median CD19+ B cells: 2.0 vs. 52.5/µl, p=0.005). Overall, CD19+ B lymphocyte numbers correlate significantly with positive SP-AbT results and were identified as predictive factor in multivariate analysis. The previously suggested threshold of 30 CD19+ B cells/µl as being predictive for SP-AbT development could be validated. SP-AbT concentration was significantly lower with older age. Furthermore, median SP-AbT were significantly lower in patients with current anti-CD38 directed therapy (median SP-AbT: 1085.4 vs. 62.05 BAU/ml, p < 0.005). Conclusions: In spite of immunodeficiency and immunosuppressive therapy, most MM patients develop SP-AbT. However, about 11% of MM patients failed to develop SP-AbT after full vaccination, and thus remain on risk for COVID-19. Higher counts of CD19+ B lymphocytes, ith a threshold of 30 CD19+ B lymphocytes/µl, are predictive for SP-AbT formation and may further help to identify patients at higher risk of insufficient vaccination response in whom control of vaccination success and potential third vaccination are particularly important. Disclosures: Bokemeyer: GlaxoSmithKline: Research Funding;Inside: Research Funding;IO Biotech: Research Funding;Eisai: Research Funding;Daiichi Sankyo: Research Funding;Gilead Sciences: Research Funding;Blueprint Medicine: Research Funding;BerGenBio: Research Funding;Janssen-Cilag: Research Funding;Isofol Medical: Research Funding;AOK Health insurance: Consultancy;GSO: Consultancy;Bayer Schering Pharma: Consultancy;Gylcotope GmbH: Research Funding;ADC Therapeutics: Research Funding;Apellis Pharmaceuticals: Research Funding;Amgen: Research Funding;Alexion Pharmaceuticals: Research Funding;Agile Therapeutics: Research Funding;Merck Serono: Consultancy, Other: Travel accomodation;Lilly/ImClone: Consultancy;Merck Sharp Dohme: Consultancy, Honoraria;AstraZeneca: Honoraria, Research Funding;BMS: Honoraria, Other: Travel accomodation, Research Funding;Bayer: Honoraria, Research Funding;Roche: Honoraria, Research Funding;Sanofi: Consultancy, Honoraria, Other: Travel accomodation;Merck KGaA: Honoraria;Abbvie: Research Funding;Boehringer Ingelheim: Research Funding;Celgene: Research Funding;Astellas: Research Funding;Karyopharm Therapeutics: Research Funding;Lilly: Research Funding;Millenium: Research Funding;MSD: Research Funding;Nektar: Research Funding;Rafael Pharmaceuticals: Research Funding;Springworks Therapeutics: Research Funding;Taiho Pharmaceutical: Research Funding;Pfizer: Other. Sinn: Incyte: Honoraria, Research Funding;Pfizer: Honoraria;Servier: Consultancy, Honoraria, Research Funding;Amgen: Consultancy, Research Funding;Astra Zenica: Consultancy, Research Funding;MSD: Consultancy, Research Funding;Sanofi: Consultancy;Bayer: Research Funding;BMS: Honoraria, Research Funding. Leypoldt: GSK: Consultancy, Other: Meeting attendance;Sanofi: Consultancy;Abbvie: Other: Meeting attendance. Weisel: Adaptiv Biotec: Consultancy;Abbvie: Consultancy;BMS: Consultancy, Honoraria, Research Funding;Celgene: Consultancy, Honoraria, Research Funding;Amgen: Consultancy, Honoraria, Research Funding;GSK: Consultancy, Honoraria;Janssen: Consultancy, Honoraria, Research Funding;Karyopharm: Honoraria;Novartis: Honoraria;Oncopeptides: Consultancy, Honoraria;Pfizer: Honoraria;Roche: Honoraria;Takeda: Honoraria;Sanofi: Consultancy, Honoraria, Research Funding.