- Email: [email protected]
Humoral response to hemagglutinin components of influenza vaccine in patients with non-Hodgkin malignant lymphoma
Vaccine 24 (2006) 6620–6623
Humoral response to hemagglutinin components of influenza vaccine in patients with non-Hodgkin malignant lymphoma Lidia B. Brydak a,b,∗ , Magdalena Machała a , Piotr Centkowski c , Krzysztof Warzocha c , Przemysław Bili´nski c b
a National Influenza Center, National Institute of Hygiene, Warsaw, Poland Chair and Department of Family Medicine, Medical University of Warsaw, Warsaw, Poland c Institute of Hematology and Blood Transfusion, Warsaw, Poland
Available online 16 June 2006
Abstract Lymphoma disease and immunosuppressive drugs used in this case cause immunity disorders increasing the risk of severe infections, including influenza. There are opinions that patients from high-risk group are not able to respond to vaccination effectively and vaccination may contribute to exacerbation of the chronic disease. The aim was to assess humoral response to influenza vaccine in 32 patients with nonHodgkin malignant lymphoma (mean age 57.2) and 32 healthy subjects (mean age 44.3). Sixteen patients were treated with immunosupressive drugs (group A) and 11 were not subjected to this therapy (group B). Levels of antihemagglutinin (anti-HA) antibodies were assessed in sera before vaccination and after 1 month by hemagglutination inhibition test. Nasal and throat swabs were collected from persons with influenza symptoms during the study to detect the etiological agent of the infection. Post-vaccination anti-HA antibody levels were significantly higher than pre-vaccination values and mean fold increases (MFI) ranged from 9.3 to 12.2 in patients and from 27.6 to 44.3 in healthy subjects. The percentage of patients with the protective anti-HA antibody titers ≥1:40 (protection rate) ranged after vaccination from 59.4% to 68.8%. The percentage of patients with at least a four-fold increase of anti-HA antibody titers (response rate) after vaccination ranged from 46.9% to 68.8%. There were no significant differences in antibody levels between patients treated with immunosuppressive drugs and those not treated. No respiratory infections were laboratory confirmed. This study showed that influenza vaccine is less immunogenic in patients with non-Hodgkin malignant lymphoma, because it induces antibody production in lower titers in comparison to the production in healthy people. Despite this, influenza vaccine should be offered to this group, considering high MFI values and response rates as well as the protective effect for individual patients. © 2006 Elsevier Ltd. All rights reserved.
1. Introduction The most effective and commonly available method of the prevention against influenza and its complications is vaccination [1–3]. Inactivated influenza vaccines prevent influenza illness in 70–90% of healthy people aged under 65 years, 60–90% in children, 50–60% in elderly living in a community and 30–40% in elderly living in nursing homes [1,3,4]. In Poland, the number of distributed doses of influenza vaccines significantly increased from 0.52 doses per 1000 inhabitants in the epidemic season 1992/1993 to over 110 doses in the season 2002/2003. On the one hand the above values mean ∗
Corresponding author. Tel.: +48 22 542 12 74; fax: +48 22 542 13 13. E-mail address: [email protected] (L.B. Brydak).
0264-410X/$ – see front matter © 2006 Elsevier Ltd. All rights reserved. doi:10.1016/j.vaccine.2006.05.100
over 211-fold increase in the vaccine use, but on the other hand it also means that only 7–10% of the total population of Poland is immunized against influenza each epidemic season. Vaccination against influenza is recommended by the national vaccination programme for different target groups, including people who are at especially high-risk for post-influenza complications [1]. Moreover, the National Influenza Center (National Institute of Hygiene, Warsaw) performs a wide range of public health activities such as lectures, leaflets for patients and brochures for physicians to increase awareness of the danger of influenza, methods of prophylaxis and recommendations for influenza vaccination, especially in the case of high-risk patients [5]. Lymphoma disease and immunosuppressive drugs used in this case cause immunity disorders increasing the risk
L.B. Brydak et al. / Vaccine 24 (2006) 6620–6623
of severe bacterial and viral infections, including influenza. Immunosuppressive treatment is a contraindication for using live vaccines, but not for inactivated vaccine and people with immmunological disorders are one of the target group for influenza vaccination [2]. Despite this, there are opinions that patients from high-risk groups, including those with immunity disorders, are not able to respond to vaccination effectively and vaccination may contribute to exacerbation of the chronic disease and patient deterioration [1,6,7]. The aim of this study was to assess humoral response to influenza vaccine in patients with non-Hodgkin malignant lymphoma in comparison with healthy subjects. The present paper presents the preliminary results of this study regarding antibody response to hemagglutinin components of the influenza vaccine.
2. Patients and methods The aim of this study was to assess humoral response to influenza vaccination in 32 patients with non-Hodgkin malignant lymphoma (age 20–84, mean 57.2) in comparison with 32 healthy subjects (age 29–67, mean 44.3). Sixteen patients (group A) were treated with immunosuppressive drugs (age 28–81, mean 55.9) and 11 patients (group B) were not subjected to this therapy (age 37–72, mean 60.7). In autumn 2004 they were vaccinated with one 0.5 ml dose of subunit influenza vaccine (‘Influvac’, Solvay Pharmaceuticals B.V.). None of them received an influenza vaccine in the previous epidemic season, i.e. 2003/2004. Levels of antihemagglutinin (anti-HA) antibodies were assessed in sera before vaccination and after 1 month by hemagglutination inhibition test (HAI) performed with the influenza strains antigenically similar to the strains included into the vaccine recommended for the season 2004/2005, i.e. A/New Caledonia/20/99 (H1N1), A/Moscow/10/99 (H3N2) and B/Hong Kong/335/01 [8,9]. Collected serum samples were frozen in −20 ◦ C and were treated with receptor destroying enzyme from Vibrio cholerae and inactivated in a 56 ◦ C water bath for 30 min before testing. Anti-HA antibody titers were read as the reciprocal of the highest serum dilution causing complete inhibition of agglutination of 0.5% turkey red blood cells. To present the results of the serological test the following serological parameters were calculated:
6621
detect the etiological agent of the infection. IF test was performed for influenza A and B, RSV, parainfluenza 1, 2, 3 and adenovirus according to the procedure provided by the producer of IF kits (Imagen, DakoCytomation). Statistical analysis of the results was performed using the non-parametric Mann–Whitney test and the Wilcoxon test (Statistica computer program, version 6.0). Informed consent was obtained from each of the subjects involved in this study as well as the approval of the appropriate Ethical Committee was received to carry out this study.
3. Results Before vaccination geometric mean titers (GMTs) of antiHA antibodies ranged from 3.5 to 3.8 in patients with nonHodgkin malignant lymphoma and from 2.1 to 2.9 in the control group of healthy people. There were no significant differences in pre-vaccination anti-HA antibody titers between patients and healthy subjects. Post-vaccination values of the serological parameters were higher in patients not treated with immunosuppressive drugs than in patients subjected to this therapy. After vaccination GMTs of anti-HA antibodies significantly increased (p < 0.05) in comparison with the prevaccination values for all antigens. Mean fold increases (MFIs) ranged from 9.3 to 12.2 in patients with lymphoma (group A: 6.7–14.5, group B: 13.3–22.3) and from 27.6 to 44.3 in healthy subjects (Figs. 1 and 2). Significantly higher (p < 0.05) post-vaccination antibody levels for all three antigens, i.e. H1, H3 and HB, were found in healthy people than in patients with lymphoma. Before vaccination protection rates, i.e. the percentage of subjects with the protective anti-HA antibody titers ≥1:40, were between 0% and 12.5% in patients with lymphoma and between 6.3% and 15.6% in healthy subjects. After vaccination protection rates increased and ranged from 59.4% to 68.8% in patients with lymphoma (group A: 37.5–62.5%, group B: 72.7–90.9%) and 90.6–96.9% in healthy people (Figs. 3 and 4). Response rates, i.e. the percentage of subjects
• geometric mean titer (GMT) of antibodies before and after vaccination; • mean fold increase (MFI) of antibody levels after vaccination; • protection rate, i.e. the proportion of subjects with anti-HA antibody titers ≥1:40 before and after vaccination; • response rate, i.e. the proportion of subjects with at least a four-fold increase of anti-HA antibody titers after vaccination [10,11]. Combined nasal and throat swabs were also collected from persons showing influenza or influenza-like symptoms during the study and immunofluorescence (IF) test was done to
Fig. 1. Mean fold increases of anti-HA antibody levels in patients with nonHodgkin malignant lymphoma after vaccination against influenza.
6622
L.B. Brydak et al. / Vaccine 24 (2006) 6620–6623
with at least a four-fold increase of anti-HA antibody titers after vaccination, ranged from 46.9% to 68.8% in patients with lymphoma (group A: 31.3–62.5%, group B: 72.7%) and 84.4–87.5% in healthy group (Figs. 3 and 4). No viral respiratory infections with influenza A and B, RSV, adenovirus or parainfluenza type 1, type 2 and type 3 were confirmed in patients with lymphoma and healthy subjects during the study.
4. Discussion and conclusions
Fig. 2. Mean fold increases of anti-HA antibody levels in patients with nonHodgkin malignant lymphoma treated with immunosuppressive drugs (T) and not treated with immunosuppressive drugs (NT) after vaccination against influenza.
Fig. 3. Protection rates and response rates before and after vaccination against influenza in patients with non-Hodgkin lymphoma.
Fig. 4. Protection rates and response rates before and after vaccination in patients with non-Hodgkin lymphoma treated with immunosuppressive drugs (T) and not treated with immunosuppressive drugs (NT).
This paper presents the results of the study on the humoral response to influenza vaccination in patients with nonHodgkin malignant lymphoma. The National Influenza Center (National Institute of Hygiene, Warsaw) together with the clinicians has already carried out studies on the immunological response to influenza vaccination in different groups of high-risk patients, including those with acute lymphoblastic leukemia, renal diseases, mild and severe hemophilia, breast cancer or in the elderly [12–19]. These studies gave promising results indicating that influenza vaccination should be recommended to these groups of patients. Nevertheless, these kind of studies in the patients with non-Hodgkin malignant lymphoma have not been conducted in Poland before. The results regarding antibody response to hemagglutinin component of the influenza vaccine showed that patients with non-Hodgkin malignant lymphoma are not able to response to influenza vaccination as well as healthy people. Influenza vaccine induced the antibody production in lower titers in these patients in comparison with healthy people. Despite this, influenza vaccine should be offered to this group, considering high MFI values, response rates as well as the protective effect for individual patients, especially those not treated with immunosuppressive drugs. In the latter group and in healthy persons all requirements of the Committee for Proprietary Medicinal Products (CPMP) for response to influenza vaccination were fulfilled. According to these requirements MFI of anti-HA antibody titers in people aged 18–60 should be >2.5, protection rates >70% and response rates >40% [20]. The only exceptions were found in patients on immunosuppressive treatment (group A), where the protection and response rate values were lower than those required by CPMP. Nevertheless, it is worth adding that differences in antibody titers between patients treated with immunosuppressive drugs and those not-treated were not statistically significant. The most studies on the humoral response to influenza vaccination focus only on the anti-HA antibodies due to the fact that these antibodies are associated with the main protective effect of vaccination. They inhibit the attachment of influenza virus to target cell receptors and neutralize virus infectivity providing complete protection against acquisition of infection or serious illness [21]. This paper presents only a part of the results obtained in the study on humoral response to influenza vaccination in patients with non-Hodgkin malignant lymphoma. The other aims of the
L.B. Brydak et al. / Vaccine 24 (2006) 6620–6623
study were to assess humoral response to neuraminidase components of the influenza vaccine and to assess the response in different classes of immunoglobulines. The results are not obtained as yet and will be published in separate articles. Nevetheless, the preliminary results presented in this paper indicate that influenza vaccination should be recommended for patients with non-Hodgkin malignant lymphoma, especially those not treated with immunosupressive drugs.
[9]
[10]
[11]
[12]
Acknowledgements The authors are grateful to Ms. Iwona Nowak for her technical assistance.
[13]
References
[14]
[1] Brydak LB, Influenza and its prophylaxis. Poznan 2003, Wydawnictwo Termedia, 2nd ed., p. 1–272 [in Polish]. [2] Centers for Disease Control and Prevention. WHO collaborating center for the surveillance, epidemiology and control of influenza. The 2004–2005 WHO influenza reagent kit for identification of influenza isolates. Atlanta; 2004. p. 1–23. [3] Nichol KL. The efficacy, effectiveness and cost-effectiveness of inactivated influenza virus vaccines. Vaccine 2003;21(16):1769– 75. [4] Monto AS, Hornbuckle K, Ohmit SE. Influenza vaccine effectiveness among elderly nursing home residents: a cohort study. Am J Epidemiol 2001;154:155–60. [5] Brydak LB, Machała M. Vaccinate yourself against influenza to avoid tragedy that happened to our grandparents. Information broschure for physicians. Warsaw: Warsaw Voice; 2005. ISBN 83-917744-5-7 [in Polish]. [6] Brydak LB, Machała M. Humoral immune reposnse to influenza vaccination in patients from high risk groups. Drugs 2000;60(1):35–53 [in Polish]. [7] Siriwardena AN, Rashid A, Johnson MRD, Dewey ME. Cluster randomised controlled tiral of an educational outreach visit to improve influenza and pneumococcal immunisation rates in primary care. Br J Gen Pract 2002;52:735–40. [8] Centers for Disease Control and Prevention. WHO Collaborating Center for the Surveillance, Epidemiology and Control of Influenza. Concepts and procedures for laboratory-based influenza surveillance. U.S.
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[19]
[20]
[21]
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Department of Health and Human Services, Public Health Service; 1982. Manuguerra J-C, Hannoun C. Influenza and other viral respiratory diseases. Surveillance and laboratory diagnosis. Paris: Institut Pasteur; 1999. p. 1–286. Glathe H, Lange W. Influenza vaccination in older patients. Immunogenicity, epidemiology and available agents. Drugs Aging 1995;6(5):368–87. Davis JR, Grillis EA. Natural or vaccine-induced immunity as a predictor of immunity in the face of natural challenge with influenza virus. Epidemiol Inf 1989;102:325–33. Brydak LB, Rokicka-Milewska R, Machała M, Jackowska T, SikorskaFic B. Immunogenicity of subunit trivalent influenza vaccine in children with acute lymphoblastic leukemia. Pediatr Infect Dis J 1998;17: 125–9. Brydak LB, Rajkowski T, Machała M, W˛eglarska J, Sieniawska M. Humoral antibody response following influenza vaccination in patients with nephrotic syndrome. Antiinfect Drugs Chemother 1998;16(2):151–5. Brydak LB, Rokicka-Milewska R, Machała M, Klukowska A, Łaguna P, Sikorska-Fic B. Efficacy of subunit trivalent influenza vaccine in previously vaccinated children suffering from hemophilia. Clin Microbiol Infect 1998;4:589–93. Brydak LB, Roszkowska-Blaim M, Machała M, Leszczy´nska B, Sieniawska M. Antibody response to influenza immunization in two consecutive epidemic seasons in patients with renal diseases. Vaccine 2000;18:3280–6. Brydak LB, Guzy J, Starzyk J, Machała M, G´oz´ d´z S. Humoral immune response after vaccination against influenza in patients with breast cancer. Support Care Cancer 2001;9:65–8. Brydak LB, Roszkowska-Blaim M, Machała M, Leszczy´nska B, Sieniawska M. Immunological response to influenza vaccination in children with renal failure. Nephrol Dial Transpl 2001;16(3):643–4. Brydak LB, Machała M, My´sliwska J, My´sliwski A, Trzonkowski P. Immune response to influenza vaccination in an elderly population. J Clin Immunol 2003;23(3):214–22. Rokicka-Milewska R, Brydak LB, Machała M, Klukowska A. Antibody response to influenza vaccine in children with severe and mild hemophila. Int J Pediatr Hematol/Oncol 2000;7(1):21–7. Committee for Proprietary Medicinal Products (CPMP): note for guidance on harmonisation of requirements for influenza vaccines. The European Agency for the Evaluation of Medicinal Products, Human Medicines Evaluation Unit (EMEA). CPMP/BWP/214/96, London, March 12, 1997. Ada GL. Immune response. General features. In: Granoff A, Webster RG, editors. Encyclopedia of virology, vol. 2, 2nd ed. Academic Press; 1999. p. 812–8.
Humoral response to hemagglutinin components of influenza vaccine in patients with non-Hodgkin malignant lymphoma Lidia B. Brydak a,b,∗ , Magdalena Machała a , Piotr Centkowski c , Krzysztof Warzocha c , Przemysław Bili´nski c b
a National Influenza Center, National Institute of Hygiene, Warsaw, Poland Chair and Department of Family Medicine, Medical University of Warsaw, Warsaw, Poland c Institute of Hematology and Blood Transfusion, Warsaw, Poland
Available online 16 June 2006
Abstract Lymphoma disease and immunosuppressive drugs used in this case cause immunity disorders increasing the risk of severe infections, including influenza. There are opinions that patients from high-risk group are not able to respond to vaccination effectively and vaccination may contribute to exacerbation of the chronic disease. The aim was to assess humoral response to influenza vaccine in 32 patients with nonHodgkin malignant lymphoma (mean age 57.2) and 32 healthy subjects (mean age 44.3). Sixteen patients were treated with immunosupressive drugs (group A) and 11 were not subjected to this therapy (group B). Levels of antihemagglutinin (anti-HA) antibodies were assessed in sera before vaccination and after 1 month by hemagglutination inhibition test. Nasal and throat swabs were collected from persons with influenza symptoms during the study to detect the etiological agent of the infection. Post-vaccination anti-HA antibody levels were significantly higher than pre-vaccination values and mean fold increases (MFI) ranged from 9.3 to 12.2 in patients and from 27.6 to 44.3 in healthy subjects. The percentage of patients with the protective anti-HA antibody titers ≥1:40 (protection rate) ranged after vaccination from 59.4% to 68.8%. The percentage of patients with at least a four-fold increase of anti-HA antibody titers (response rate) after vaccination ranged from 46.9% to 68.8%. There were no significant differences in antibody levels between patients treated with immunosuppressive drugs and those not treated. No respiratory infections were laboratory confirmed. This study showed that influenza vaccine is less immunogenic in patients with non-Hodgkin malignant lymphoma, because it induces antibody production in lower titers in comparison to the production in healthy people. Despite this, influenza vaccine should be offered to this group, considering high MFI values and response rates as well as the protective effect for individual patients. © 2006 Elsevier Ltd. All rights reserved.
1. Introduction The most effective and commonly available method of the prevention against influenza and its complications is vaccination [1–3]. Inactivated influenza vaccines prevent influenza illness in 70–90% of healthy people aged under 65 years, 60–90% in children, 50–60% in elderly living in a community and 30–40% in elderly living in nursing homes [1,3,4]. In Poland, the number of distributed doses of influenza vaccines significantly increased from 0.52 doses per 1000 inhabitants in the epidemic season 1992/1993 to over 110 doses in the season 2002/2003. On the one hand the above values mean ∗
Corresponding author. Tel.: +48 22 542 12 74; fax: +48 22 542 13 13. E-mail address: [email protected] (L.B. Brydak).
0264-410X/$ – see front matter © 2006 Elsevier Ltd. All rights reserved. doi:10.1016/j.vaccine.2006.05.100
over 211-fold increase in the vaccine use, but on the other hand it also means that only 7–10% of the total population of Poland is immunized against influenza each epidemic season. Vaccination against influenza is recommended by the national vaccination programme for different target groups, including people who are at especially high-risk for post-influenza complications [1]. Moreover, the National Influenza Center (National Institute of Hygiene, Warsaw) performs a wide range of public health activities such as lectures, leaflets for patients and brochures for physicians to increase awareness of the danger of influenza, methods of prophylaxis and recommendations for influenza vaccination, especially in the case of high-risk patients [5]. Lymphoma disease and immunosuppressive drugs used in this case cause immunity disorders increasing the risk
L.B. Brydak et al. / Vaccine 24 (2006) 6620–6623
of severe bacterial and viral infections, including influenza. Immunosuppressive treatment is a contraindication for using live vaccines, but not for inactivated vaccine and people with immmunological disorders are one of the target group for influenza vaccination [2]. Despite this, there are opinions that patients from high-risk groups, including those with immunity disorders, are not able to respond to vaccination effectively and vaccination may contribute to exacerbation of the chronic disease and patient deterioration [1,6,7]. The aim of this study was to assess humoral response to influenza vaccine in patients with non-Hodgkin malignant lymphoma in comparison with healthy subjects. The present paper presents the preliminary results of this study regarding antibody response to hemagglutinin components of the influenza vaccine.
2. Patients and methods The aim of this study was to assess humoral response to influenza vaccination in 32 patients with non-Hodgkin malignant lymphoma (age 20–84, mean 57.2) in comparison with 32 healthy subjects (age 29–67, mean 44.3). Sixteen patients (group A) were treated with immunosuppressive drugs (age 28–81, mean 55.9) and 11 patients (group B) were not subjected to this therapy (age 37–72, mean 60.7). In autumn 2004 they were vaccinated with one 0.5 ml dose of subunit influenza vaccine (‘Influvac’, Solvay Pharmaceuticals B.V.). None of them received an influenza vaccine in the previous epidemic season, i.e. 2003/2004. Levels of antihemagglutinin (anti-HA) antibodies were assessed in sera before vaccination and after 1 month by hemagglutination inhibition test (HAI) performed with the influenza strains antigenically similar to the strains included into the vaccine recommended for the season 2004/2005, i.e. A/New Caledonia/20/99 (H1N1), A/Moscow/10/99 (H3N2) and B/Hong Kong/335/01 [8,9]. Collected serum samples were frozen in −20 ◦ C and were treated with receptor destroying enzyme from Vibrio cholerae and inactivated in a 56 ◦ C water bath for 30 min before testing. Anti-HA antibody titers were read as the reciprocal of the highest serum dilution causing complete inhibition of agglutination of 0.5% turkey red blood cells. To present the results of the serological test the following serological parameters were calculated:
6621
detect the etiological agent of the infection. IF test was performed for influenza A and B, RSV, parainfluenza 1, 2, 3 and adenovirus according to the procedure provided by the producer of IF kits (Imagen, DakoCytomation). Statistical analysis of the results was performed using the non-parametric Mann–Whitney test and the Wilcoxon test (Statistica computer program, version 6.0). Informed consent was obtained from each of the subjects involved in this study as well as the approval of the appropriate Ethical Committee was received to carry out this study.
3. Results Before vaccination geometric mean titers (GMTs) of antiHA antibodies ranged from 3.5 to 3.8 in patients with nonHodgkin malignant lymphoma and from 2.1 to 2.9 in the control group of healthy people. There were no significant differences in pre-vaccination anti-HA antibody titers between patients and healthy subjects. Post-vaccination values of the serological parameters were higher in patients not treated with immunosuppressive drugs than in patients subjected to this therapy. After vaccination GMTs of anti-HA antibodies significantly increased (p < 0.05) in comparison with the prevaccination values for all antigens. Mean fold increases (MFIs) ranged from 9.3 to 12.2 in patients with lymphoma (group A: 6.7–14.5, group B: 13.3–22.3) and from 27.6 to 44.3 in healthy subjects (Figs. 1 and 2). Significantly higher (p < 0.05) post-vaccination antibody levels for all three antigens, i.e. H1, H3 and HB, were found in healthy people than in patients with lymphoma. Before vaccination protection rates, i.e. the percentage of subjects with the protective anti-HA antibody titers ≥1:40, were between 0% and 12.5% in patients with lymphoma and between 6.3% and 15.6% in healthy subjects. After vaccination protection rates increased and ranged from 59.4% to 68.8% in patients with lymphoma (group A: 37.5–62.5%, group B: 72.7–90.9%) and 90.6–96.9% in healthy people (Figs. 3 and 4). Response rates, i.e. the percentage of subjects
• geometric mean titer (GMT) of antibodies before and after vaccination; • mean fold increase (MFI) of antibody levels after vaccination; • protection rate, i.e. the proportion of subjects with anti-HA antibody titers ≥1:40 before and after vaccination; • response rate, i.e. the proportion of subjects with at least a four-fold increase of anti-HA antibody titers after vaccination [10,11]. Combined nasal and throat swabs were also collected from persons showing influenza or influenza-like symptoms during the study and immunofluorescence (IF) test was done to
Fig. 1. Mean fold increases of anti-HA antibody levels in patients with nonHodgkin malignant lymphoma after vaccination against influenza.
6622
L.B. Brydak et al. / Vaccine 24 (2006) 6620–6623
with at least a four-fold increase of anti-HA antibody titers after vaccination, ranged from 46.9% to 68.8% in patients with lymphoma (group A: 31.3–62.5%, group B: 72.7%) and 84.4–87.5% in healthy group (Figs. 3 and 4). No viral respiratory infections with influenza A and B, RSV, adenovirus or parainfluenza type 1, type 2 and type 3 were confirmed in patients with lymphoma and healthy subjects during the study.
4. Discussion and conclusions
Fig. 2. Mean fold increases of anti-HA antibody levels in patients with nonHodgkin malignant lymphoma treated with immunosuppressive drugs (T) and not treated with immunosuppressive drugs (NT) after vaccination against influenza.
Fig. 3. Protection rates and response rates before and after vaccination against influenza in patients with non-Hodgkin lymphoma.
Fig. 4. Protection rates and response rates before and after vaccination in patients with non-Hodgkin lymphoma treated with immunosuppressive drugs (T) and not treated with immunosuppressive drugs (NT).
This paper presents the results of the study on the humoral response to influenza vaccination in patients with nonHodgkin malignant lymphoma. The National Influenza Center (National Institute of Hygiene, Warsaw) together with the clinicians has already carried out studies on the immunological response to influenza vaccination in different groups of high-risk patients, including those with acute lymphoblastic leukemia, renal diseases, mild and severe hemophilia, breast cancer or in the elderly [12–19]. These studies gave promising results indicating that influenza vaccination should be recommended to these groups of patients. Nevertheless, these kind of studies in the patients with non-Hodgkin malignant lymphoma have not been conducted in Poland before. The results regarding antibody response to hemagglutinin component of the influenza vaccine showed that patients with non-Hodgkin malignant lymphoma are not able to response to influenza vaccination as well as healthy people. Influenza vaccine induced the antibody production in lower titers in these patients in comparison with healthy people. Despite this, influenza vaccine should be offered to this group, considering high MFI values, response rates as well as the protective effect for individual patients, especially those not treated with immunosuppressive drugs. In the latter group and in healthy persons all requirements of the Committee for Proprietary Medicinal Products (CPMP) for response to influenza vaccination were fulfilled. According to these requirements MFI of anti-HA antibody titers in people aged 18–60 should be >2.5, protection rates >70% and response rates >40% [20]. The only exceptions were found in patients on immunosuppressive treatment (group A), where the protection and response rate values were lower than those required by CPMP. Nevertheless, it is worth adding that differences in antibody titers between patients treated with immunosuppressive drugs and those not-treated were not statistically significant. The most studies on the humoral response to influenza vaccination focus only on the anti-HA antibodies due to the fact that these antibodies are associated with the main protective effect of vaccination. They inhibit the attachment of influenza virus to target cell receptors and neutralize virus infectivity providing complete protection against acquisition of infection or serious illness [21]. This paper presents only a part of the results obtained in the study on humoral response to influenza vaccination in patients with non-Hodgkin malignant lymphoma. The other aims of the
L.B. Brydak et al. / Vaccine 24 (2006) 6620–6623
study were to assess humoral response to neuraminidase components of the influenza vaccine and to assess the response in different classes of immunoglobulines. The results are not obtained as yet and will be published in separate articles. Nevetheless, the preliminary results presented in this paper indicate that influenza vaccination should be recommended for patients with non-Hodgkin malignant lymphoma, especially those not treated with immunosupressive drugs.
[9]
[10]
[11]
[12]
Acknowledgements The authors are grateful to Ms. Iwona Nowak for her technical assistance.
[13]
References
[14]
[1] Brydak LB, Influenza and its prophylaxis. Poznan 2003, Wydawnictwo Termedia, 2nd ed., p. 1–272 [in Polish]. [2] Centers for Disease Control and Prevention. WHO collaborating center for the surveillance, epidemiology and control of influenza. The 2004–2005 WHO influenza reagent kit for identification of influenza isolates. Atlanta; 2004. p. 1–23. [3] Nichol KL. The efficacy, effectiveness and cost-effectiveness of inactivated influenza virus vaccines. Vaccine 2003;21(16):1769– 75. [4] Monto AS, Hornbuckle K, Ohmit SE. Influenza vaccine effectiveness among elderly nursing home residents: a cohort study. Am J Epidemiol 2001;154:155–60. [5] Brydak LB, Machała M. Vaccinate yourself against influenza to avoid tragedy that happened to our grandparents. Information broschure for physicians. Warsaw: Warsaw Voice; 2005. ISBN 83-917744-5-7 [in Polish]. [6] Brydak LB, Machała M. Humoral immune reposnse to influenza vaccination in patients from high risk groups. Drugs 2000;60(1):35–53 [in Polish]. [7] Siriwardena AN, Rashid A, Johnson MRD, Dewey ME. Cluster randomised controlled tiral of an educational outreach visit to improve influenza and pneumococcal immunisation rates in primary care. Br J Gen Pract 2002;52:735–40. [8] Centers for Disease Control and Prevention. WHO Collaborating Center for the Surveillance, Epidemiology and Control of Influenza. Concepts and procedures for laboratory-based influenza surveillance. U.S.
[15]
[16]
[17]
[18]
[19]
[20]
[21]
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