Content
Special Groups
Immunocompromised Patiens
Table 21.6 Immunisation for Patients with Acute Leukemia, Lymphoma, Multiple Myeloma and Solid Tumors
cGvHD ; chronic graft versus host disease
Footnote:
The risk of severe infection is influenced by the underlying malignancy and the cancer specific therapies.
Immune response to the vaccine is reduced during chemotherapy therefore, vaccination should be avoided during treatment. Patients given inactivated vaccines >14 days before antineoplastic treatment do not require revaccination, unless vaccination status is incomplete or refresher vaccination is indicated. Patients vaccinated during chemotherapy should be revaccinated ≥ 3 months after completion of chemotherapy and ≥ 6 months after anti-B cell antibodies
Live vaccines, e.g. against MMR, yellow fever and varicella, are generally contraindicated during chemotherapy [including maintenance therapy with monoclonal antibodies or immunomodulatory agents, e.g. lenalidomide, as well as conditions with significant immunosuppression]. After completion of immunosuppressive therapy, live vaccines against MMR and varicella might be considered after assessment of antibody titres.
a – Administer inactivated influenza vaccine (IIV) annually to patients with hematological malignancies (strong, moderate) or solid tumor malignancies (strong, low) except those receiving anti-B-cell antibodies such as rituximab or alemtuzumab (weak, low). The Infectious Diseases Society of America also suggests that IIV be avoided in patients receiving intensive chemotherapy such as for induction or consolidation therapy for acute leukemia (weak, low). However, we favor giving an inactivated influenza vaccine to such patients given the need for annual administration to protect against circulating seasonal strains of influenza. Administration of inactivated vaccines other than IIV, which are routinely recommended for healthy children in the annually updated United States Centers for Disease Control and Prevention (CDC) recommendations, can be considered for children with malignancies who are receiving maintenance chemotherapy (weak, low). However, vaccines administered while receiving cancer chemotherapy should not be considered valid doses (strong, low). Administration of indicated inactivated vaccines 2 or more weeks prior to chemotherapy is preferred. IIV can be administered ≤ 3 months after chemotherapy, but response rate may be low. Two doses of influenza vaccine may be more immunogenic than one and are well tolerated in children and young adults. VACANCE trial suggest a second administration of influenza vaccine in cancer patients as this increased seroconversion from 44% to 73%. It is also recommended that family members and caretakers also receive annual inactivated influenza vaccination if there is contact with those who are immunosuppressed. The observed side effects of the inactivated influenza vaccine are similar in all populations in that they are generally mild and may include soreness or pain around the injection site, fever, fatigue, or myalgia.
^^ If pretreatment vaccination is not feasible, we recommend vaccination after the first chemotherapy cycle and repetition 3 months after chemotherapy, PCV13 is more immunogenic than PPV23. Due to a lower immunogenic response, patients receiving treatment for multiple myeloma, Hodgkin and non-Hodgkin lymphomas, and cGVHD, as well as those who have undergone total-body irradiation, should be vaccinated with PCV13 instead of PPV23. For patients aged ≥ 19 years who have received PPV23, PCV13 should be administered after an internal of ≥ 1 years after the last PPV23 dose (weak, low).
$ Adult patients with malignancies are at increased risk for HiB infections, particularly HiB-induced pneumonia.
***HBV vaccine should not be given while patients are on immunosuppressive therapy. As immune-response for HBV-vaccine was shown to be impaired in this population [23], patients with AL should receive several doses (AIII) vaccination against HBV is recommended in lymphoma, myeloma patients in case of incomplete vaccination status or if a vaccination refreshing is required (BII). Inadequate immune-response should always be considered and in individual patients, passive immunisation against HBV could offer short-term protection.
Assessing titres of diphtheria, tetanus and HBV might be useful after chemotherapy.
# These live viral vaccines should not be administered during chemotherapy unless indicated based on CDC recommendations AND the patient is not immunosuppressed AND there will be an interval of ≥ 4 weeks prior to initiation of chemotherapy. Adult cancer patients seronegative for VZV show increased rates of complications (e.g. dissemination, mortality), if primarily infected. Only one study investigated immunity and safety of VZV vaccine in (pediatric) leukemia patients and showed benefits regarding immunity against chickenpox for at least 3 years.
§ Although MMR vaccine has been given safely three months after completion of chemotherapy, data on the safety, immunogenicity, and efficacy of varicella or zoster vaccine after completion of chemotherapy are not available.
References
- Arrowood, J. R., & Hayney, M. S. (2002). Immunization recommendations for adults with cancer. Annals of Pharmacotherapy, 36(7-8), 1219-1229.
- Ljungman, P. (2012). Vaccination of immunocompromised patients. Clinical Microbiology and Infection, 18, 93-99.
- Practices, A. C. o. I. (2012). Recommended adult immunization schedule: United States, 2012. Annals of internal medicine, 156(3), 211.
- Rieger, C., Liss, B., Mellinghoff, S., Buchheidt, D., Cornely, O., Egerer, G., Heinz, W., Hentrich, M., Maschmeyer, G., & Mayer, K. (2018). 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). Annals of Oncology, 29(6), 1354-1365.
- Sandherr, M., Hentrich, M., von Lilienfeld-Toal, M., Massenkeil, G., Neumann, S., Penack, O., Biehl, L., & Cornely, O. A. (2015). Antiviral prophylaxis in patients with solid tumours and haematological malignancies—update of the Guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO). Annals of Hematology, 94(9), 1441-1450.
- Tsang, V. (2012). Vaccination Recommendations for the Hematology and Oncology and Post–Stem Cell Transplant Populations. Journal of the Advanced Practitioner in Oncology, 3(2), 71.
Relationship between Monoclonal Antibodies, Kinase Inhibitors and Immune Checkpoint Blockade and Vaccination
Monoclonal antibodies against CD20 result in near complete B cell depletion for up to 6 months after therapy. Although the majority of patients show complete recovery of B cells 1 year after therapy, prolonged B cell depletion and hypogammaglobulinemia may occur, making vaccination strategies challenging.
As a functioning B cell compartment is required for an adequate immune response, vaccination within the first 6 months after anti-CD20 therapy is generally discouraged.
Within the first year after anti-CD20 therapy, assessment of antibody titers and revaccination if indicated might be an effective strategy to achieve protective antibody levels despite a diminished immune response. Particularly in case of seasonal influenza vaccine after anti-CD20 therapy, administration of a second booster vaccine has been shown to significantly increase humoral immune response.
While most data on vaccination strategies have been obtained with the oldest anti-CD20 antibody rituximab, it is generally accepted that these recommendations be transferable to other anti-CD20 antibodies such as ofatumumab or obinutuzumab as well as to other temporarily B cell depleting therapies such as the anti-CD3xCD19 bispecific T-cell engager blinatumomab.
Due to the different pathways affected, the effect of kinase inhibitors on immune response to vaccination is entirely dependent on the drug in question. In a small study of patients with metastatic renal cell carcinoma treated with the tyrosine kinase inhibitors sorafenib or sunitinib, no significant difference regarding protective antibody responses after influenza vaccination could be observed compared with healthy controls. Another small study with chronic lymphocytic leukemia patients treated with ibrutinib showed seroprotective titers against common influenza virus strains after vaccination in up to 74% of patients. Therefore, decisions on vaccination need to be made on a case-by-case basis. In patients receiving kinase inhibitors, assessment of antibody titers and revaccination (if necessary) is recommended for adequate seroprotection.
Due to their novelty, data on vaccination strategies in patients treated by immune checkpoint inhibitors, such as anti-PD1, anti-PD-L1 or anti-CTLA4 antibodies, are limited. However, considering their mechanism of action, immune checkpoint inhibitors are likely to enhance rather than diminish immune response and have even been safely explored as vaccine adjuvants. As patients receiving immune checkpoint inhibitors are still at increased risk of infections due to their underlying malignancy, they should receive all appropriate vaccines at the earliest convenience to avoid infectious complications or delay in therapy.
References
- Cabanillas, F., Liboy, I., Pavia, O., & Rivera, E. (2006). High incidence of non-neutropenic infections induced by rituximab plus fludarabine and associated with hypogammaglobulinemia: a frequently unrecognized and easily treatable complication. Annals of Oncology, 17(9), 1424-1427.
- Chiou, W.-Y., Hung, S.-K., Lai, C.-L., Lin, H.-Y., Su, Y.-C., Chen, Y.-C., Shen, B.-J., Chen, L.-C., Tsai, S.-J., & Lee, M.-S. (2015). Effect of 23-valent pneumococcal polysaccharide vaccine inoculated during anti-cancer treatment period in elderly lung cancer patients on community-acquired pneumonia hospitalization: a nationwide population-based cohort study. Medicine, 94(26).
- de Lavallade, H., Garland, P., Sekine, T., Hoschler, K., Marin, D., Stringaris, K., Loucaides, E., Howe, K., Szydlo, R., & Kanfer, E. (2011). Repeated vaccination is required to optimize seroprotection against H1N1 in the immunocompromised host. Haematologica, 96(2), 307-314.
- Madan, R. A., Mohebtash, M., Arlen, P. M., Vergati, M., Rauckhorst, M., Steinberg, S. M., Tsang, K. Y., Poole, D. J., Parnes, H. L., & Wright, J. J. (2012). Ipilimumab and a poxviral vaccine targeting prostate-specific antigen in metastatic castration-resistant prostate cancer: a phase 1 dose-escalation trial. The lancet oncology, 13(5), 501-508.
- McLaughlin, P., Grillo-López, A. J., Link, B. K., Levy, R., Czuczman, M. S., Williams, M. E., Heyman, M. R., Bence-Bruckler, I., White, C. A., & Cabanillas, F. (1998). Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program. Journal of clinical oncology, 16(8), 2825-2833.
- Mulder, S. F., Jacobs, J. F., Nordkamp, M. A. O., Galama, J. M., Desar, I. M., Torensma, R., Teerenstra, S., Mulders, P. F., Vissers, K. C., & Punt, C. J. (2011). Cancer patients treated with sunitinib or sorafenib have sufficient antibody and cellular immune responses to warrant influenza vaccination. Clinical Cancer Research, 17(13), 4541-4549.
- Rieger, C., Liss, B., Mellinghoff, S., Buchheidt, D., Cornely, O., Egerer, G., Heinz, W., Hentrich, M., Maschmeyer, G., & Mayer, K. (2018). 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). Annals of Oncology, 29(6), 1354-1365.
- Sun, C., Gao, J., Couzens, L., Tian, X., Farooqui, M. Z., Eichelberger, M. C., & Wiestner, A. (2016). Seasonal influenza vaccination in patients with chronic lymphocytic leukemia treated with ibrutinib. JAMA oncology, 2(12), 1656-1657.
Table 21.7 Immunisation For Blood And Marrow Transplant Recipients (Allogeneic And Autologous)
Footnote:
a if not specified, otherwise, the interval between dose is 1 month,
b the interval between dose is 1-2 month,
c Check titres 4-8 weeks after last dose of post-transplant vaccine; if anti-HBs is < 10 mIU/ml, an additional 3 doses should be considered, but the benefit of this second series of vaccination is uncertain. A high dose formulation is preferred for these booster doses.
cGvHD; chronic graft versus host disease.
NOTES
- Vaccination schedules are similar for allogeneic and autologous HCT recipients, but grading of recommendation changes for some vaccines.
- Live attenuated vaccines (MMR, varicella) should not be given within the first 2 years after HSCT during active Graft versus host disease (GvHD) (DIII). Limited data regarding safety and efficacy.
- Inactivated vaccine can be given if the patient has chronic GVHD.
- Inactivated Polio form (IPV) and oral Polio vaccine (OPV) are not interchangeable.
- In patients receiving prednisone ≥ 0.5 mg/kg bodyweight per day as part of a combination therapy or a three-agent immunosuppressive treatment is given, vaccination may be postponed until immunosuppression is reduced to a double combination or prednisone < 0.5 mg/ kg bodyweight daily in order to achieve a better vaccine response (BIII).
- Following a complete revaccination program, regular assessment of seroprotection against diphtheria, poliomyelitis, tetanus, measles and HBV every 4-5 years is recommended in patients after HSCT (BIII).
- Pneumococcal vaccine: There are 2 types of pneumococcal vaccine – conjugate vaccine (PCV13) and polysaccharide vaccine (PPV23). PCV13 is used for the primary series because the immunological response to conjugate vaccines is generally more immunogenic than polysaccharide vaccines but, the spectrum of protection is narrower and therefore the subsequent dose of PPV23 is given to broaden the immune response. The PPV23 covers 23 strains but is less immunogenic and may elicit inadequate response. It may be beneficial to use PPV23 as the fourth dose to broaden the immune response.
- For transplant patients who wish to travel abroad, immunisation may be necessary. Patients should seek advice from their respective transplantation teams. Vaccines that should be safe for blood and marrow transplant patients intending to travel include:
• Typhoid – The oral form is contraindicated
• Cholera – Not recommended because of low protective efficacy
• Hepatitis A – Both active and passive are safe
• The following vaccines are contraindicated: Yellow fever, Japanese encephalitis, oral polio vaccines - HBV
Before allogeneic HSCT, patients who are negative for all HBV markers that are transplanted with a graft from an anti-HBc positive donor should be vaccinated if possible (B III) and could additionally receive anti-HBV immunoglobulins; - 6 months after allogeneic and autologous HSCT, patients who were negative for HBV before transplantation and patients who were vaccinated before transplant but lost their immunity at 6 months should be vaccinated (6–12 months after transplantation 3 doses should be administered 0, 1, and 6 months apart), (B II t); patients infected with HBV before HSCT (HBsAg negative and anti-HBc positive) should be assessed regularly for anti-HBs antibody titres and should be vaccinated if they have unprotective titres (< 10 IU/ml) (B III); if anti-HBs titres are 10mI/ml 1-2months after the initial series of 3 vaccine doses, a second series of 3 doses should be considered (CIII). In persons that are primary non-responders, a repeat vaccine series using high-dose vaccine can be administered. If seroconversion is not achieved, counselling regarding post-exposure prophylaxis and avoidance of high-risk behavior can be provided.
- Donor vaccination may improve the immunity of patient’s post-transplant especially in the case of tetanus, pneumococcus and Hib. However, no recommendations can be made in view of the practical difficulties and ethical issues
References
- Cordonnier, C., Einarsdottir, S., Cesaro, S., Di Blasi, R., Mikulska, M., Rieger, C., de Lavallade, H., Gallo, G., Lehrnbecher, T., & Engelhard, D. (2019). Vaccination of haemopoietic stem cell transplant recipients: guidelines of the 2017 European Conference on Infections in Leukaemia (ECIL 7). The Lancet Infectious Diseases, 19(6), e200-e212.
- de la Cámara, R. (2019). Vaccinations. In E. Carreras, C. Dufour, M. Mohty, & N. Kröger (Eds.), The EBMT Handbook: Hematopoietic Stem Cell Transplantation and Cellular Therapies (pp. 207-219). Springer International Publishing. https://doi.org/10.1007/978-3-030-02278-5_29
- Ljungman, P., Cordonnier, C., Einsele, H., Englund, J., Machado, C., Storek, J., & Small, T. (2009). Vaccination of hematopoietic cell transplant recipients. Bone marrow transplantation, 44(8), 521-526.
- Rieger, C., Liss, B., Mellinghoff, S., Buchheidt, D., Cornely, O., Egerer, G., Heinz, W., Hentrich, M., Maschmeyer, G., & Mayer, K. (2018). 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). Annals of Oncology, 29(6), 1354-1365.
- Rubin, L. G., Levin, M. J., Ljungman, P., Davies, E. G., Avery, R., Tomblyn, M., Bousvaros, A., Dhanireddy, S., Sung, L., & Keyserling, H. (2014). 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clinical infectious diseases, 58(3), e44-e100.
- Ullmann, A. J., Schmidt-Hieber, M., Bertz, H., Heinz, W. J., Kiehl, M., Krüger, W., Mousset, S., Neuburger, S., Neumann, S., & Penack, O. (2016). Infectious diseases in allogeneic haematopoietic stem cell transplantation: prevention and prophylaxis strategy guidelines 2016. Annals of Hematology, 95(9), 1435-1455.
Table 21.8 Immunisation For Solid Organ Transplant Adult Recipients
Footnote:
IIV, inactivated Influenza vaccine; LAIV, Live attenuated Influenza (inactivated); IPV, Inactivated Polio Vaccine; HPV, human papilloma virus; MMR, Measles-Mumps-Rubella, MSM, men who have sex with men
HBV: High-dose vaccine should be used pre-transplant in dialysis patients and after SOT.5 In general, anti-HBs titers should be monitored post-transplant and booster doses (1–3 boosters) should be administered if titers fall below protective levels (<10 IU/mL). In persons that are primary non-responders, a repeat vaccine series using high-dose vaccine can be administered. If seroconversion is not achieved, counselling regarding post-exposure prophylaxis and avoidance of high-risk behavior can be provided.
References
- Danziger-Isakov, L., Kumar, D., & Practice, A. I. D. C. o. (2013). Vaccination in solid organ transplantation. American Journal of Transplantation, 13(s4), 311-317.
- Rubin, L. G., Levin, M. J., Ljungman, P., Davies, E. G., Avery, R., Tomblyn, M., Bousvaros, A., Dhanireddy, S., Sung, L., & Keyserling, H. (2014). 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clinical infectious diseases, 58(3), e44-e100.
- Stucchi, R. S., Lopes, M. H., Kumar, D., & Manuel, O. (2018). Vaccine recommendations for solid-organ transplant recipients and donors. Transplantation, 102(2S), S72-S80.