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• W2954328980 abstract "We thank Laura Sticchi and colleagues1Sticchi L Gabutti G Castagnola E Possible pitfalls of the 2017 ECIL guidelines.Lancet Infect Dis. 2019; 19: 575Summary Full Text Full Text PDF PubMed Scopus (1) Google Scholar for their pertinent comments on the 2017 European Conference on Infections in Leukaemia (ECIL 7) vaccination guidelines for patients with haematological diseases, including haematopoietic stem-cell transplant (HSCT) recipients.2Cordonnier C Einarsdottir S Cesaro S 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-e212Summary Full Text Full Text PDF PubMed Scopus (143) Google Scholar, 3Mikulska M Cesaro S de Lavallade H et al.Vaccination of patients with haematological malignancies who did not have transplantations: guidelines from the 2017 European Conference on Infections in Leukaemia (ECIL 7).Lancet Infect Dis. 2019; 19: e188-e199Summary Full Text Full Text PDF PubMed Scopus (69) Google Scholar We answer their comments about antibody assessment below and address all other issues in the appendix. Sticchi and colleagues first debate the use of antibodies for assessing vaccine immunity. The reasons our recommendations are mostly based on laboratory endpoints were explained in our Series papers:2Cordonnier C Einarsdottir S Cesaro S 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-e212Summary Full Text Full Text PDF PubMed Scopus (143) Google Scholar, 3Mikulska M Cesaro S de Lavallade H et al.Vaccination of patients with haematological malignancies who did not have transplantations: guidelines from the 2017 European Conference on Infections in Leukaemia (ECIL 7).Lancet Infect Dis. 2019; 19: e188-e199Summary Full Text Full Text PDF PubMed Scopus (69) Google Scholar for most vaccines, undertaking prospective trials that are powered enough to show the clinical benefit of vaccination in these populations is not possible. Until now, the largest prospective vaccine trial after HSCT included 251 patients.4Cordonnier C Ljungman P Juergens C et al.Immunogenicity, safety, and tolerability of 13-valent pneumococcal conjugate vaccine followed by 23-valent pneumococcal polysaccharide vaccine in recipients of allogeneic hematopoietic stem cell transplant aged ≥2: an open-label study.Clin Infect Dis. 2015; 61: 313-323Crossref PubMed Scopus (66) Google Scholar Therefore, although prospective trials collect data on the occurrence of vaccine-preventable diseases, their primary objective is always a laboratory endpoint, except in cases of an outbreak when the infection incidence is high. We agree with Sticchi and colleagues that there are weaknesses in the use of antibodies for assessment of pre-existing immunity or vaccination efficacy, particularly for pathogens such as pertussis, which is why we did not suggest an individual assessment of anti-pertussis antibodies, although they have been assessed in prospective trials after HSCT. Sticchi and colleagues also comment on the interest in opsonophagocytosis assays over ELISAs for assessing antipneumococcal and antipolyribosylribitol Haemophilus influenzae type b (Hib) antibody titres. We agree that opsonophagocytosis assays are rarely available in routine clinical practice; however, several prospective studies4Cordonnier C Ljungman P Juergens C et al.Immunogenicity, safety, and tolerability of 13-valent pneumococcal conjugate vaccine followed by 23-valent pneumococcal polysaccharide vaccine in recipients of allogeneic hematopoietic stem cell transplant aged ≥2: an open-label study.Clin Infect Dis. 2015; 61: 313-323Crossref PubMed Scopus (66) Google Scholar, 5Cordonnier C Labopin M Jansen KU et al.Relationship between IgG titers and opsonocytophagocytic activity of anti-pneumococcal antibodies after immunization with the 7-valent conjugate vaccine in allogeneic stem cell transplant.Bone Marrow Transplant. 2010; 45: 1423-1426Crossref PubMed Scopus (22) Google Scholar have shown correlations between IgG ELISA antibody titres and opsonophagocytosis assay titres for all pneumococcal vaccine-induced antibodies assessed in allogeneic HSCT recipients. The largest study on the 13-valent pneumococcal conjugate vaccine (PCV13) in HSCT recipients, done in 54 paediatric and 162 adult patients, confirmed this strong correlation for all PCV13 antibodies, except for a small discrepancy for serotype 3 in children.4Cordonnier C Ljungman P Juergens C et al.Immunogenicity, safety, and tolerability of 13-valent pneumococcal conjugate vaccine followed by 23-valent pneumococcal polysaccharide vaccine in recipients of allogeneic hematopoietic stem cell transplant aged ≥2: an open-label study.Clin Infect Dis. 2015; 61: 313-323Crossref PubMed Scopus (66) Google Scholar As for Hib anti-polyribosylribitol antibodies, we agree that their titres might sometimes not strictly correlate with their functions; however, first, after allogeneic HSCT, as we established in our 1987 publication6Aucouturier P Barra A Intrator L et al.Long lasting IgG subclass and antibacterial polysaccharide antibody deficiency after allogeneic bone marrow transplantation.Blood. 1987; 70: 779-785Crossref PubMed Google Scholar (before Hib vaccine was routine in children), an association exists between the onset of Hib disease and low anti-polyribosylribitol antibody titres assessed by ELISA,6Aucouturier P Barra A Intrator L et al.Long lasting IgG subclass and antibacterial polysaccharide antibody deficiency after allogeneic bone marrow transplantation.Blood. 1987; 70: 779-785Crossref PubMed Google Scholar irrespective of functional tests. Second, although anti-polyribosylribitol antibody titres decrease rapidly after vaccination in healthy children, nearly all those vaccinated maintain protective concentrations.7Collins S Litt D Almond R et al.Haemophilus influenzae type b (Hib) seroprevalence and current epidemiology in England and Wales.J Infect. 2018; 76: 335-341Summary Full Text Full Text PDF PubMed Scopus (18) Google Scholar Finally, a large UK study using 2693 serum samples from individuals of all ages strongly suggested that anti-polyribosylribitol antibody titres at a concentration of 1 μg/mL or higher are protective of Hib disease.8Ladhani S Ramsay M Flood J et al.Haemophilus influenzae serotype B (Hib) seroprevalence in England and Wales in 2009.Euro Surveill. 2012; 1720313Crossref PubMed Scopus (17) Google Scholar The benefit of functional tests over ELISA is probably limited to the so-called grey zone of protection between 0·15 and 1 μg/mL in ELISA. In such a case in an HSCT recipient, without functional tests in routine practice, we would recommend a booster vaccination. In summary, we do not think functional tests are warranted in routine clinical practice (except for meningococcal immunity) because ELISAs can mostly provide useful individual patient-level information about the extent of protection, although no cutoff of protection has been established in this population. Sticchi and colleagues question the assessment of antibodies against tetanus, diphtheria, and pertussis (Tdp) and Hib during long-term follow-up. After the initial regimen of three doses of Tdp vaccine, we recommend at least a booster programme according to the national recommendations for individuals of that age. However, the long-term (eg, 5-year) persistence of immunity after vaccination for diphtheria and tetanus after HSCT is good for tetanus but not for diphtheria, especially in patients who have extensive and chronic graft-versus-host disease.9Inaba H Hartford CM Pei D et al.Longitudinal analysis of antibody response to immunization in paediatric survivors after allogeneic haematopoietic stem cell transplantation.Br J Haematol. 2012; 156: 109-117Crossref PubMed Scopus (36) Google Scholar Therefore, we hypothesise that high-risk patients (eg, those with extensive and chronic graft-versus-host disease, cord blood transplant recipients, or those receiving rituximab after transplant) might need boosters of vaccines earlier than is recommended in the healthy population. Sticchi and colleagues also believe there was a contradiction between table 2 and the main text about assessment of pneumococcal antibodies,1Sticchi L Gabutti G Castagnola E Possible pitfalls of the 2017 ECIL guidelines.Lancet Infect Dis. 2019; 19: 575Summary Full Text Full Text PDF PubMed Scopus (1) Google Scholar, 2Cordonnier C Einarsdottir S Cesaro S 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-e212Summary Full Text Full Text PDF PubMed Scopus (143) Google Scholar which is not the case. In table 2, we gave the initial recommended programme for pneumococcal vaccination, and in the text we recommend the assessment of anti-pneumococcal antibodies from 24 months. We agree with Sticchi and colleagues that many questions are still pending and encourage them to develop prospective vaccine studies in patients with haematological diseases. CC reports grants and personal fees from Merck, and grants from Astellas, outside the submitted work. MM reports personal fees from Pfizer, Gilead, Biotest, Janssen, and Merck, outside the submitted work. PL reports grants from Merck and Astellas, outside the submitted work. All other authors declare no competing interests. Download .pdf (.3 MB) Help with pdf files Supplementary appendix Possible pitfalls of the 2017 ECIL guidelinesWe read with interest the Series papers by Catherine Cordonnier and colleagues1 on the 2017 European Conference on Infections in Leukaemia (ECIL) guidelines for vaccination of haemopoietic stem-cell transplant (HSCT) recipients and by Malgorzata Mikulska and colleagues2 on ECIL guidelines for vaccination of patients with haematological malignancies. These papers are very useful for everyday practice, but in our opinion, some points should be further discussed (appendix). Full-Text PDF Vaccination of patients with haematological malignancies who did not have transplantations: guidelines from the 2017 European Conference on Infections in Leukaemia (ECIL 7)Patients with haematological malignancies are at high risk of infection because of various mechanisms of humoral and cell-mediated immune deficiencies, which mainly depend on underlying disease and specific therapies. Some of these infections are vaccine preventable. However, these malignancies are different from each other, and the treatment approaches are diverse and rapidly evolving, so it is difficult to have a common programme for vaccination in a haematology ward. Additionally, because of insufficient training about the topic, vaccination is an area often neglected by haematologists, and influenced by cultural differences, even among health-care workers, in compliance to vaccines. Full-Text PDF Vaccination of haemopoietic stem cell transplant recipients: guidelines of the 2017 European Conference on Infections in Leukaemia (ECIL 7)Infection is a main concern after haemopoietic stem cell transplantation (HSCT) and a major cause of transplant-related mortality. Some of these infections are preventable by vaccination. Most HSCT recipients lose their immunity to various pathogens as soon as the first months after transplant, irrespective of the pre-transplant donor or recipient vaccinations. Vaccination with inactivated vaccines is safe after transplantation and is an effective way to reinstate protection from various pathogens (eg, influenza virus and Streptococcus pneumoniae), especially for pathogens whose risk of infection is increased by the transplant procedure. Full-Text PDF" @default.
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