Recommendations for vaccination in multiple myeloma: a consensus of the European Myeloma Network.
Journal
Leukemia
ISSN: 1476-5551
Titre abrégé: Leukemia
Pays: England
ID NLM: 8704895
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
08
04
2020
accepted:
05
08
2020
revised:
24
07
2020
pubmed:
21
8
2020
medline:
14
1
2021
entrez:
21
8
2020
Statut:
ppublish
Résumé
Vaccination is one of the most successful medical interventions that has saved the life of millions of people. Vaccination is particularly important in patients with multiple myeloma, who have an increased risk of infections due to the disease-inherent immune suppression, and because of the immune suppressive effects of therapy. Hence, all appropriate measures should be exploited, to elicit an effective immune response to common pathogens like influenza, pneumococci, varicella zoster virus, and to those bacteria and viruses (haemophilus influenzae, meningococci, and hepatitis) that frequently may pose a significant risk to patients with multiple myeloma. Patients after autologous, and specifically after allogeneic transplantation have severely reduced antibody titers, and therefore require a broader spectrum of vaccinations. Response to vaccination in myeloma often is less vigorous than in the general population, mandating either measurement of the postvaccination antibody titers and/or repeating the vaccination. Here, we compile the existing data on vaccination in multiple myeloma and provide recommendations for clinical practice.
Identifiants
pubmed: 32814840
doi: 10.1038/s41375-020-01016-0
pii: 10.1038/s41375-020-01016-0
pmc: PMC7787974
doi:
Substances chimiques
Immunosuppressive Agents
0
Vaccines
0
Types de publication
Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
31-44Références
Alemu A, Singh M, Blumberg C, Richards JO, Oaks MK, Thompson MA. Multiple myeloma vaccination patterns in a large health system: a pilot study. J Patient Cent Res Rev. 2017;4:53–9.
pubmed: 31413971
pmcid: 6664370
Brioli A, Klaus M, Sayer H, Scholl S, Ernst T, Hilgendorf I, et al. The risk of infections in multiple myeloma before and after the advent of novel agents: a 12-year survey. Ann Hematol. 2019;98:713–22.
pubmed: 30680505
Kristinsson SY, Tang M, Pfeiffer RM, Bjorkholm M, Goldin LR, Blimark C, et al. Monoclonal gammopathy of undetermined significance and risk of infections: a population-based study. Haematologica. 2012;97:854–8.
pubmed: 22180421
pmcid: 3366650
Blimark C, Holmberg E, Mellqvist UH, Landgren O, Bjorkholm M, Hultcrantz M, et al. Multiple myeloma and infections: a population-based study on 9253 multiple myeloma patients. Haematologica. 2015;100:107–13.
pubmed: 25344526
pmcid: 4281323
National Center for Immunization and Respiratory Diseases, General Best Practice Guidelines for Immunization: Best Practices Guidance of the Advisory Committee on Immunization Practices (ACIP): Altered Immunocompetence. 2019. https://www.cdc.gov/vaccines/hcp/acip-recs/general-recs/immunocompetence.html . Accessed 1 Mar 2020.
World Health Organisation: Vaccines and Immunization; recommendations for routine immunization. 2019. https://www.who.int/immunization/policy/immunization_tables/en/ . Accessed 1 Mar 2020.
National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in OncologyTM. Prevention and Treatment of Cancer-Related Infections. 2020. https://www.nccn.org/professionals/physician_gls/pdf/infections.pdf . Accessed 1 Mar 2020.
Rieger CT, Liss B, Mellinghoff S, Buchheidt D, Cornely OA, Egerer G, et al. Anti-infective vaccination strategies in patients with hematologic malignancies or solid tumors-Guideline of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO). Ann Oncol. 2018;29:1354–65.
pubmed: 29688266
pmcid: 6005139
Khan AR, Khan S, Zimmerman V, Baddour LM, Tleyjeh IM. Quality and strength of evidence of the Infectious Diseases Society of America clinical practice guidelines. Clin Infect Dis. 2010;51:1147–56.
pubmed: 20946067
Karlsson J, Andreasson B, Kondori N, Erman E, Riesbeck K, Hogevik H, et al. Comparative study of immune status to infectious agents in elderly patients with multiple myeloma, Waldenstrom’s macroglobulinemia, and monoclonal gammopathy of undetermined significance. Clin Vaccine Immunol. 2011;18:969–77.
pubmed: 21508164
pmcid: 3122605
Sasaki S, Sullivan M, Narvaez CF, Holmes TH, Furman D, Zheng NY, et al. Limited efficacy of inactivated influenza vaccine in elderly individuals is associated with decreased production of vaccine-specific antibodies. J Clin Investig. 2011;121:3109–19.
pubmed: 21785218
Murasko DM, Bernstein ED, Gardner EM, Gross P, Munk G, Dran S, et al. Role of humoral and cell-mediated immunity in protection from influenza disease after immunization of healthy elderly. Exp Gerontol. 2002;37:427–39.
pubmed: 11772530
Iuliano AD, Roguski KM, Chang HH, Muscatello DJ, Palekar R, Tempia S, et al. Estimates of global seasonal influenza-associated respiratory mortality: a modelling study. Lancet. 2018;391:1285–300.
pubmed: 29248255
Suzuki Y. Sialobiology of influenza: molecular mechanism of host range variation of influenza viruses. Biol Pharm Bull. 2005;28:399–408.
pubmed: 15744059
Chen YQ, Wohlbold TJ, Zheng NY, Huang M, Huang Y, Neu KE, et al. Influenza infection in humans induces broadly cross-reactive and protective neuraminidase-reactive antibodies. Cell. 2018;173:417–29.e410.
pubmed: 29625056
pmcid: 5890936
Krammer F, Fouchier RAM, Eichelberger MC, Webby RJ, Shaw-Saliba K, Wan H, et al. NAction! How can neuraminidase-based immunity contribute to better influenza virus vaccines? mBio. 2018;9:e02332–17.
pubmed: 29615508
pmcid: 5885027
Devarajan P, Bautista B, Vong AM, McKinstry KK, Strutt TM, Swain SL. New insights into the generation of CD4 memory may shape future vaccine strategies for influenza. Front Immunol. 2016;7:136.
pubmed: 27148257
pmcid: 4827017
Nordoy T, Aaberge IS, Husebekk A, Samdal HH, Steinert S, Melby H, et al. Cancer patients undergoing chemotherapy show adequate serological response to vaccinations against influenza virus and Streptococcus pneumoniae. Med Oncol. 2002;19:71–8.
pubmed: 12180483
Pollyea DA, Brown JM, Horning SJ. Utility of influenza vaccination for oncology patients. J Clin Oncol. 2010;28:2481–90.
pubmed: 20385981
Bitterman R, Eliakim-Raz N, Vinograd I, Zalmanovici Trestioreanu A, Leibovici L, Paul M. Influenza vaccines in immunosuppressed adults with cancer. Cochrane Database Syst Rev. 2018;2:Cd008983.
pubmed: 29388675
Robertson JD, Nagesh K, Jowitt SN, Dougal M, Anderson H, Mutton K, et al. Immunogenicity of vaccination against influenza, Streptococcus pneumoniae and Haemophilus influenzae type B in patients with multiple myeloma. Br J Cancer. 2000;82:1261–5.
pubmed: 10755398
pmcid: 2374477
Sanada Y, Yakushijin K, Nomura T, Chayahara N, Toyoda M, Minami Y, et al. A prospective study on the efficacy of two-dose influenza vaccinations in cancer patients receiving chemotherapy. Jpn J Clin Oncol. 2016;46:448–52.
pubmed: 26977053
Hahn M, Schnitzler P, Schweiger B, Kunz C, Ho AD, Goldschmidt H, et al. Efficacy of single versus boost vaccination against influenza virus in patients with multiple myeloma. Haematologica. 2015;100:e285–8.
pubmed: 25820335
pmcid: 4486243
Branagan AR, Duffy E, Albrecht RA, Cooper DL, Seropian S, Parker TL, et al. Clinical and serologic responses after a two-dose series of high-dose influenza vaccine in plasma cell disorders: a prospective, single-arm trial. Clin Lymphoma Myeloma Leuk. 2017;17:296–304.e292.
pubmed: 28343904
pmcid: 5413398
de Lavallade H, Garland P, Sekine T, Hoschler K, Marin D, Stringaris K, et al. Repeated vaccination is required to optimize seroprotection against H1N1 in the immunocompromised host. Haematologica. 2011;96:307–14.
pubmed: 20971824
Dolan GP, Harris RC, Clarkson M, Sokal R, Morgan G, Mukaigawara M, et al. Vaccination of healthcare workers to protect patients at increased risk of acute respiratory disease: summary of a systematic review. Influenza Other Respir Viruses. 2013;7 Suppl 2: 93–6.
World Health Organization, Geneva 2019: Global influenza strategy 2019–2030. https://www.who.int/influenza/global_influenza_strategy_2019_2030/en/ . Accessed 27 Nov 2019.
Centers for Disease Control and Prevention, National Center for Immunization and Respiratory Diseases (NCIRD). 2019. https://www.cdc.gov/flu/prevent/vaccinations.htm . Accessed 27 Nov 2019.
Referenced with permission from the NCCN Guidelines for Prevention and Treatment of Cancer-Related Infections V.1.2020. National Comprehensive Cancer Network, Inc. 2019. All rights reserved. Accessed 4 Mar 2020. www.NCCN.org . NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
World Health Organisation: Recommendations for routine immunization - summary tables, table 4. 2019. https://www.who.int/immunization/policy/Immunization_routine_table4_FR.pdf?ua=1 . Accessed 28 Feb 2020.
Centers for Disease Control and Prevention, National Center for Immunization and Respiratory Diseases (NCIRD). 2016. https://www.cdc.gov/vaccines/adults/rec-vac/hcw.html . Accessed 28 Feb 2020.
Maltezou HC, Poland GA. Immunization of health-care providers: necessity and public health policies. Healthcare. 2016;4:47.
pmcid: 5041048
Alemu A, Richards JO, Oaks MK, Thompson MA. Vaccination in multiple myeloma: review of current literature. Clin Lymphoma Myeloma Leuk. 2016;16:495–502.
pubmed: 27364264
Drgona L, Gudiol C, Lanini S, Salzberger B, Ippolito G, Mikulska M. ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an infectious diseases perspective (Agents targeting lymphoid or myeloid cells surface antigens [II]: CD22, CD30, CD33, CD38, CD40, SLAMF-7 and CCR4). Clin Microbiol Infect. 2018;24:S83–94.
pubmed: 29572070
Schmader K. Herpes zoster. Clin Geriatr Med. 2016;32:539–53.
pubmed: 27394022
Pandit A, Leblebjian H, Hammond SP, Laubach JP, Richardson PG, Baden LR, et al. Safety of live-attenuated measles-mumps-rubella and herpes zoster vaccination in multiple myeloma patients on maintenance lenalidomide or bortezomib after autologous hematopoietic cell transplantation. Bone Marrow Transplant. 2018;53:942–5.
pubmed: 29426830
Winston DJ, Mullane KM, Cornely OA, Boeckh MJ, Brown JW, Pergam SA, et al. Inactivated varicella zoster vaccine in autologous haemopoietic stem-cell transplant recipients: an international, multicentre, randomised, double-blind, placebo-controlled trial. Lancet. 2018;391:2116–27.
pubmed: 29856344
Cunningham AL, Lal H, Kovac M, Chlibek R, Hwang SJ, Diez-Domingo J, et al. Efficacy of the herpes zoster subunit vaccine in adults 70 years of age or older. N Engl J Med. 2016;375:1019–32.
pubmed: 27626517
Dagnew AF, Ilhan O, Lee WS, Woszczyk D, Kwak JY, Bowcock S, et al. Immunogenicity and safety of the adjuvanted recombinant zoster vaccine in adults with haematological malignancies: a phase 3, randomised, clinical trial and post-hoc efficacy analysis. Lancet Infect Dis. 2019;19:988–1000.
pubmed: 31399377
Centers for Disease Control and Prevention, National Center for Immunization and Respiratory Diseases, Department of Health and Human Services. Vaccine Information Statement (Interim), Hepatitis A Vaccine (7/28/2020), 42 U.S.C. § 300aa-26. https://www.cdc.gov/vaccines/hcp/vis/vis-statements/hep-a.html . Accessed 28 Jul 2020.
Terrault NA, Lok ASF, McMahon BJ, Chang KM, Hwang JP, Jonas MM, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018;67:1560–99.
pubmed: 29405329
pmcid: 5975958
Lee S, Kim HW, Kim KH. Antibodies against hepatitis A and hepatitis B virus in intravenous immunoglobulin products. J Korean Med Sci. 2016;31:1937–42.
pubmed: 27822932
pmcid: 5102857
Hwang JP, Somerfield MR, Alston-Johnson DE, Cryer DR, Feld JJ, Kramer BS, et al. Hepatitis B virus screening for patients with cancer before therapy: American Society of Clinical Oncology Provisional Clinical Opinion Update. J Clin Oncol. 2015;33:2212–20.
pubmed: 25964247
pmcid: 4477791
Lampertico P, Agarwal K, Berg T, Buti M, Janssen HLA, Papatheodoridis G, et al. European Association for the Study of the Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2017;67:370–98.
Sarmati L, Andreoni M, Antonelli G, Arcese W, Bruno R, Coppola N, et al. Recommendations for screening, monitoring, prevention, prophylaxis and therapy of hepatitis B virus reactivation in patients with haematologic malignancies and patients who underwent haematologic stem cell transplantation-a position paper. Clin Microbiol Infect. 2017;23:935–40.
pubmed: 28668466
Duncan JD, Urbanowicz RA, Tarr AW, Ball JK. Hepatitis C virus vaccine: challenges and prospects. Vaccines. 2020;8:1–23.
Kontio M, Jokinen S, Paunio M, Peltola H, Davidkin I. Waning antibody levels and avidity: implications for MMR vaccine-induced protection. J Infect Dis. 2012;206:1542–8.
pubmed: 22966129
Ljungman P, Lewensohn-Fuchs I, Hammarstrom V, Aschan J, Brandt L, Bolme P, et al. Long-term immunity to measles, mumps, and rubella after allogeneic bone marrow transplantation. Blood. 1994;84:657–63.
pubmed: 8025290
Ljungman P, Cordonnier C, Einsele H, Englund J, Machado CM, Storek J, et al. Vaccination of hematopoietic cell transplant recipients. Bone Marrow Transplant. 2009;44:521–6.
pubmed: 19861986
Simell B, Lahdenkari M, Reunanen A, Kayhty H, Vakevainen M. Effects of ageing and gender on naturally acquired antibodies to pneumococcal capsular polysaccharides and virulence-associated proteins. Clin Vaccin Immunol. 2008;15:1391–7.
Geno KA, Gilbert GL, Song JY, Skovsted IC, Klugman KP, Jones C, et al. Pneumococcal capsules and their types: past, present, and future. Clin Microbiol Rev. 2015;28:871–99.
pubmed: 26085553
pmcid: 4475641
Bahuaud M, Bodilis H, Malphettes M, Maugard Landre A, Matondo C, Bouscary D, et al. Immunogenicity and persistence of the 13-valent pneumococcal conjugate vaccine (PCV13) in patients with untreated smoldering multiple myeloma (SMM): a pilot study. Heliyon. 2017;3:e00441.
pubmed: 29159320
pmcid: 5681344
Bonten MJ, Huijts SM, Bolkenbaas M, Webber C, Patterson S, Gault S, et al. Polysaccharide conjugate vaccine against pneumococcal pneumonia in adults. N Engl J Med. 2015;372:1114–25.
pubmed: 25785969
Hinge M, Ingels HA, Slotved HC, Molle I. Serologic response to a 23-valent pneumococcal vaccine administered prior to autologous stem cell transplantation in patients with multiple myeloma. APMIS. 2012;120:935–40.
pubmed: 23009118
Mustafa SS, Shah D, Bress J, Jamshed S. Response to PCV13 vaccination in patients with multiple myeloma versus healthy controls. Hum Vaccines Immunother. 2019;15:452–4.
Pasiarski M, Sosnowska-Pasiarska B, Grywalska E, Stelmach-Goldys A, Kowalik A, Gozdz S, et al. Immunogenicity and safety of the 13-valent pneumococcal conjugate vaccine in patients with monoclonal gammopathy of undetermined significance—relationship with selected immune and clinical parameters. Clin Interv Aging. 2019;14:1741–9.
pubmed: 31631993
pmcid: 6790629
Karlsson J, Roalfe L, Hogevik H, Zancolli M, Andreasson B, Goldblatt D, et al. Poor correlation between pneumococcal IgG and IgM titers and opsonophagocytic activity in vaccinated patients with multiple myeloma and Waldenstrom’s macroglobulinemia. Clin Vaccin Immunol. 2016;23:379–85.
Lode H, Schmoele-Thoma B, Gruber W, Ahlers N, Fernsten P, Baker S, et al. Dose-ranging study of a single injection of pneumococcal conjugate vaccine (1 x, 2 x, or 4 x) in healthy subjects aged 70 years or older. Vaccine. 2011;29:4940–6.
pubmed: 21596077
Harboe ZB, Dalby T, Weinberger DM, Benfield T, Molbak K, Slotved HC, et al. Impact of 13-valent pneumococcal conjugate vaccination in invasive pneumococcal disease incidence and mortality. Clin Infect Dis. 2014;59:1066–73.
pubmed: 25034421
Andrews NJ, Waight PA, George RC, Slack MP, Miller E. Impact and effectiveness of 23-valent pneumococcal polysaccharide vaccine against invasive pneumococcal disease in the elderly in England and Wales. Vaccine. 2012;30:6802–8.
pubmed: 23000122
High NJ, Fan F, Schwartzman JD. Chapter 97—haemophilus influenzae. Molecular medical microbiology, 2nd ed. vol. 3. Amsterdam: Academic Press; 2015. pp 1709–28.
Nix EB, Hawdon N, Gravelle S, Biman B, Brigden M, Malik S, et al. Risk of invasive Haemophilus influenzae type b (Hib) disease in adults with secondary immunodeficiency in the post-Hib vaccine era. Clin Vaccine Immunol. 2012;19:766–71.
pubmed: 22398246
pmcid: 3346318
Palazzo M, Shah GL, Copelan O, Seier K, Devlin SM, Maloy M, et al. Revaccination after autologous hematopoietic stem cell transplantation is safe and effective in patients with multiple myeloma receiving lenalidomide maintenance. Biol Blood Marrow Transplant. 2018;24:871–6.
pubmed: 29288818
Feldman C, Anderson R. Meningococcal pneumonia: a review. Pneumonia. 2019;11:3.
pubmed: 31463180
pmcid: 6708554
Bennett DE, Meyler KL, Cafferkey MT, Cunney RJ. Diversity of meningococci associated with invasive meningococcal disease in the Republic of Ireland over a 19 year period, 1996–2015. PloS ONE. 2020;15:e0228629.
pubmed: 32053601
pmcid: 7018037
Kristinsson SY, Gridley G, Hoover RN, Check D, Landgren O. Long-term risks after splenectomy among 8,149 cancer-free American veterans: a cohort study with up to 27 years follow-up. Haematologica. 2014;99:392–8.
pubmed: 24056815
pmcid: 3912973
Einarsdottir S, Ljungman P, Kaijser B, Nicklasson M, Horal P, Norder H, et al. Humoral immunity to tetanus, diphtheria and polio in adults after treatment for hematological malignancies. Vaccine. 2020;38:1084–8.
pubmed: 31787417
Ljungman P, Wiklund-Hammarsten M, Duraj V, Hammarstrom L, Lonnqvist B, Paulin T, et al. Response to tetanus toxoid immunization after allogeneic bone marrow transplantation. J Infect Dis. 1990;162:496–500.
pubmed: 2197342
Parkkali T, Ruutu T, Stenvik M, Kuronen T, Kayhty H, Hovi T, et al. Loss of protective immunity to polio, diphtheria and Haemophilus influenzae type b after allogeneic bone marrow transplantation. APMIS. 1996;104:383–8.
pubmed: 8703445
Suzuki N, Mizue N, Hori T, Hatakeyama N, Kudoh T, Tsutsumi H. Pertussis in adolescence after unrelated cord blood transplantation. Bone Marrow Transplant. 2003;32:967.
pubmed: 14562002
Nordoy T, Husebekk A, Aaberge IS, Jenum PA, Samdal HH, Flugsrud LB, et al. Humoral immunity to viral and bacterial antigens in lymphoma patients 4-10 years after high-dose therapy with ABMT. Serological responses to revaccinations according to EBMT guidelines. Bone Marrow Transplant. 2001;28:681–7.
pubmed: 11704791
Renaud L, Schraen S, Fouquet G, Guidez S, Demarquette H, Nudel M, et al. Response to pneumococcal vaccination in multiple myeloma. Cancer Med. 2019;8:3822–30.
pubmed: 31145552
pmcid: 6639194
Cordonnier C, Einarsdottir S, Cesaro S, Di Blasi R, Mikulska M, Rieger C, et al. Vaccination of haemopoietic stem cell transplant recipients: guidelines of the 2017 European Conference on Infections in Leukaemia (ECIL 7). Lancet Infect Dis. 2019;19:e200–12.
pubmed: 30744963
Inazawa N, Hori T, Nojima M, Saito M, Igarashi K, Yamamoto M, et al. Virus reactivations after autologous hematopoietic stem cell transplantation detected by multiplex PCR assay. J Med Virol. 2017;89:358–62.
pubmed: 27364410
Rubin LG, Levin MJ, Ljungman P, Davies EG, Avery R, Tomblyn M, et al. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis. 2014;58:309–18.
pubmed: 24421306
Gueller S, Allwinn R, Mousset S, Martin H, Wieters I, Herrmann E, et al. Enhanced immune response after a second dose of an AS03-adjuvanted H1N1 influenza A vaccine in patients after hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2011;17:1546–50.
pubmed: 21324375
Cordonnier C, Labopin M, Chesnel V, Ribaud P, De La Camara R, Martino R, et al. Randomized study of early versus late immunization with pneumococcal conjugate vaccine after allogeneic stem cell transplantation. Clin Infect Dis. 2009;48:1392–401.
pubmed: 19368505
Frerichs KA, Bosman PWC, Nijhof IS, Zweegman S, van de Donk N. Cytomegalovirus reactivation in a patient with extensively pretreated multiple myeloma during daratumumab treatment. Clin Lymphoma Myeloma Leuk. 2019;19:e9–11.
pubmed: 30392824
Hartkamp A, Mulder AH, Rijkers GT, van Velzen-Blad H, Biesma DH. Antibody responses to pneumococcal and haemophilus vaccinations in patients with B-cell chronic lymphocytic leukaemia. Vaccine. 2001;19:1671–7.
pubmed: 11166890
Noonan K, Rudraraju L, Ferguson A, Emerling A, Pasetti MF, Huff CA, et al. Lenalidomide-induced immunomodulation in multiple myeloma: impact on vaccines and antitumor responses. Clin Cancer Res. 2012;18:1426–34.
pubmed: 22241792
pmcid: 3640365
Maltezou HC, Poland GA. Immunization of healthcare personnel in Europe: time to move forward with a common program. Vaccine. 2020;8:3187–90.
Government of Canada. Immunization of workers: Canadian Immunization Guide for Health Professionals. 2019. https://www.canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-part-3-vaccination-specific-populations/page-11-immunization-workers.html#p3c10t1 . Accessed 31 Mar 2020.
U.S. Department of Health and Human Services (HHS), Office of Infectious Disease and HIV/AIDS Policy. 2020. https://www.vaccines.gov/basics/safety/side_effects . Accessed 29 Feb 2020.
Plotkin SA, Offit PA, DeStefano F, Larson HJ, Arora NK, Zuber PLF, et al. The science of vaccine safety: summary of meeting at Wellcome Trust. Vaccine. 2020;38:1869–80.
pubmed: 31987690