INTRODUCTION — Prevention of infection is of paramount importance to the ever-increasing population of patients who have impaired immunity. Infection in these patients often results in excessive morbidity and mortality, and antimicrobial therapy is often less effective than in the unimpaired host [1]. Although immunization appears to be an obvious way to prevent infection, many patients with impaired immunity are unable to mount a protective immune response to active vaccination. Furthermore, immunization with live-virus vaccines may result in unchecked proliferation of attenuated strains.

The risk of acquiring infection and the inability to prevent infection by immunization are directly related to the patient's "net state of immunosuppression" or severity of disease. The greater the degree of immunosuppression, the less likely the patient is to respond to immunization. Although certain existing vaccines provide some benefit to the immunocompromised patient, a vaccine response cannot be assumed. Successful protection of the immunocompromised adult may require the use of vaccines and/or passive immunization (ie, immune globulin) as well as adjunctive measures, such as antiviral drug prophylaxis during influenza A outbreaks. (See "Prevention of seasonal influenza with antiviral drugs in adults" and "Seasonal influenza in children: Management".)

The rationale for immunizing adults who have undergone chemotherapy for treatment of hematologic malignancies and solid tumors or who have other immunocompromising conditions will be reviewed here. Issues related to immunizations in patients who have had hematopoietic cell transplants or solid organ transplants or who are infected with HIV as well as in healthy children and adults are discussed separately. (See "Immunizations in hematopoietic cell transplant candidates and recipients" and "Immunizations in solid organ transplant candidates and recipients" and "Immunizations in patients with HIV" and "Standard immunizations for nonpregnant adults" and "Standard immunizations for children and adolescents: Overview".)

GENERAL APPROACH — Adults with cancer are at increased risk of serious infection, although the degree of risk varies based on underlying malignancy and type of immunosuppressive treatments used. Many of these infections are vaccine preventable. Patients with hematologic malignancies tend to be more immunocompromised than those with solid tumors. However, patients with solid tumors are also at risk of infection on the basis of debility, malnutrition, and, in some cases, anatomic obstruction (eg, lung masses obstructing bronchial drainage).

Vaccines are important for patients with cancer, but ideally should not be given during periods of immunosuppression from chemotherapy immunotherapy because, at such times, they may not be effective and live vaccines may result in vaccine-derived infections. The timing of immunizations in patients with cancer is discussed below. (See 'Timing of immunizations' below.)

Treatment for many cancers has intensified greatly in recent years, resulting in improved patient outcomes, but few studies of immunity and vaccination have been published during this time period. Immunization recommendations for immunocompromised patients in the United States have been developed by the Infectious Diseases Society of America (IDSA) [2]. The United States Advisory Committee on Immunization Practices (ACIP) also includes recommendations for immunocompromised patients in their guidelines (figure 1) [3]. Our recommendations are generally in keeping with those of the IDSA and the ACIP.

When both inactivated and live formulations of a given vaccine are available, the inactivated formulation is preferred in patients with cancer.

TIMING OF IMMUNIZATIONS — The timing of administration of immunizations in patients with cancer is summarized as follows [2,3]:

●Immunizing prior to chemotherapy – All indicated vaccines should be given to adult cancer patients before initiation of chemotherapy, before therapy with other immunosuppressive drugs, and before radiation or splenectomy, when feasible (figure 1). Indicated inactivated vaccines should be given ≥2 weeks prior to chemotherapy, and indicated live-virus vaccines should be given ≥4 weeks prior to chemotherapy.

●Avoidance of live vaccines during chemotherapy – Patients with cancer receiving chemotherapy or other immunosuppressive therapy should not receive live-virus vaccines because of the risk of vaccine-derived infections.

●Inactivated immunizations during chemotherapy – Inactivated vaccines should generally be avoided in patients with cancer receiving chemotherapy or other immunosuppressive therapy because they may not be effective. 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. Detailed recommendations about the timing of influenza vaccination administration are presented below. (See 'Influenza vaccine' below.)

If other inactivated vaccines are given during chemotherapy, they should not be considered valid doses unless protective antibodies are documented. In such patients, vaccines should be readministered after the recovery of immune competence. Revaccination of individuals after chemotherapy or radiation is generally unnecessary if the prior vaccination occurred before chemotherapy, with the exception of hematopoietic cell transplant recipients. (See "Immunizations in hematopoietic cell transplant candidates and recipients".)

●Immunizing following completion of chemotherapy – Patients with leukemia, lymphoma, or other malignancies whose disease is in remission, who haven't received anti-B cell antibodies (eg, rituximab, alemtuzumab), and whose chemotherapy has been terminated for at least three months may receive inactivated vaccines as well as live-virus vaccines such as the vaccines for varicella; measles, mumps, rubella; measles, mumps, rubella, and varicella; and zoster according to age-specific recommendations. In patients who have received anti-B cell antibodies, administration of inactivated and live vaccines should be delayed for at least six months.

INACTIVATED VACCINES

Tetanus toxoid, diphtheria toxoid, and pertussis vaccines — Many oncology patients receiving chemotherapy are not protected against tetanus, diphtheria, and pertussis. In one report, for example, only 59 percent of patients being treated for acute leukemia were protected against tetanus [4]. Little is known about response to tetanus and diphtheria immunization in the heterogeneous population of cancer patients, although, in one study, children on maintenance chemotherapy had an immune response similar to that observed in healthy children [5].

Tetanus and diphtheria booster immunizations should be considered for all patients with cancer. In addition, adults who have not been vaccinated with the acellular pertussis vaccine should receive the vaccine containing tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap). Tetanus and diphtheria toxoid (Td) or Tdap should ideally be given before starting treatment and preferably not during cycles of intensive chemotherapy. Pertussis vaccination in children is discussed separately. (See "Tetanus-diphtheria toxoid vaccination in adults" and "Pertussis infection in adolescents and adults: Treatment and prevention" and "Diphtheria, tetanus, and pertussis immunization in children 7 through 18 years of age" and "Diphtheria, tetanus, and pertussis immunization in children 6 weeks through 6 years of age", section on 'Schedules'.)

Polio vaccine — The inactivated polio vaccine is the only poliovirus vaccine recommended for immunodeficient individuals and their household contacts [6]. However, a protective immune response cannot be assured in patients who are immunodeficient at the time of vaccination. (See "Poliovirus vaccination".)

Pneumococcal vaccine — Pneumococcal vaccine should be administered to oncology patients prior to starting treatment and should be avoided particularly during cycles of intense chemotherapy because a poor response can be anticipated. (See 'Timing of immunizations' above.)

The 23-valent pneumococcal polysaccharide vaccine (PPSV23; Pneumovax) has been recommended for immunocompromised adults in the United States for many years, but in 2012 the United States Advisory Committee on Immunization Practices (ACIP) began also recommending the 13-valent pneumococcal conjugate vaccine (PCV13; Prevnar 13) for individuals aged 19 or older with certain high-risk conditions, including cancer (table 1) [7]. The Infectious Diseases Society of America (IDSA) guidelines for vaccination of the immunocompromised hosts endorse this approach [2].

In accordance with the ACIP and the IDSA, we recommend that adults with cancer receive PCV13 in addition to PPSV23 as follows (algorithm 1 and table 1) [2,7]:

●For patients who have not previously received either PCV13 or PPSV23, a single dose of PCV13 should be given, followed by a dose of PPSV23 at least eight weeks later.

●For patients who have previously received one or more doses of PPSV23, a single dose of PCV13 should be given one or more years after the last PPSV23 dose was received.

●For patients who require additional doses of PPSV23, the first such dose should be given no sooner than eight weeks after PCV13 and at least five years after the most recent dose of PPSV23.

Pneumococcal vaccination in adults is discussed in greater detail separately. (See "Pneumococcal vaccination in adults".)

Pneumococcal conjugate vaccines that contain a different number of serotypes (eg, PCV10) are used in some countries in Europe and elsewhere. Patients should be vaccinated against pneumococcus according to their national guidelines.

Pneumococcal infections are an important cause of morbidity and mortality in oncology patients [8]. Responses to PPSV23 vary but are better (even close to normal) if the vaccine is administered prior to the onset of therapy [9-13]. Serum IgG-2 concentrations predict the ability to respond to the vaccine [14].

Response to PPSV23 is greatly diminished after chemotherapy. Vaccine responses are particularly poor after initiating cancer treatment in patients with leukemia [15] and head and neck cancers [13]. Among patients with Hodgkin lymphoma, for example, vaccine responses remain impaired for as long as seven years after treatment [10]. At least in Hodgkin lymphoma, priming with the seven-valent pneumococcal conjugate vaccine (PCV7; Prevnar 7) appears to improve the response to the subsequent administration of PPSV23 [16]. Additional evidence supporting the use of pneumococcal conjugate vaccination in high-risk adults comes from a randomized trial of PCV7 in HIV-infected patients [17,18]. (See "Immunizations in patients with HIV".)

Haemophilus influenzae vaccine — Adult cancer patients are not at significant risk of developing Haemophilus influenzae type b (Hib) disease unless they undergo hematopoietic cell transplantation (HCT). Hib immunization is therefore not routinely recommended for adult cancer patients unless they undergo HCT. (See "Immunizations in hematopoietic cell transplant candidates and recipients", section on 'Haemophilus influenzae' and "Prevention of Haemophilus influenzae type b infection", section on 'High risk of invasive Hib disease'.)

Meningococcal vaccine — Meningococcal vaccination is recommended for individuals at increased risk for meningococcal infection, such as children between 11 and 18 years of age and certain other groups (college freshmen living in dormitories, individuals traveling to countries where Neisseria meningitidis is hyperendemic or epidemic, patients with terminal complement component deficiencies or anatomic or functional asplenia, and others).

There are no specific recommendations for patients with cancer, but any adult cancer patient who has another indication for meningococcal vaccination should be vaccinated [19]. Vaccine response may be suboptimal in cancer patients [2,3]. The appropriate formulation and vaccine schedule depends upon the individual's age and underlying illness. This is discussed in detail separately. (See "Meningococcal vaccination in children and adults", section on 'Indications and schedules in the United States'.)

Influenza vaccine — Adults with cancer should receive an inactivated influenza vaccine annually [2,20,21]. An exception is patients who are receiving anti-B cell antibodies (eg, rituximab, alemtuzumab) since immunogenicity is so poor; vaccine administration should be delayed for at least six months in such patients [2]. Although inactivated vaccines are generally avoided in patients receiving intensive chemotherapy (eg, induction or consolidation chemotherapy for acute leukemia), we favor giving an inactivated influenza vaccine to such patients given the need for annual administration to protect against circulating seasonal strains of influenza. Immunization of family members and hospital staff is also strongly recommended. The recommendations do not support administration of a second dose of the influenza vaccine within the same season [21].

As the immune response to the influenza vaccine is likely to be impaired in patients receiving chemotherapy, the vaccine is optimally administered at least two weeks before chemotherapy starts or following completion of chemotherapy if the patient is expected to finish chemotherapy early in the influenza season. If neither of these options is possible, we suggest immunizing patients about a week after the start of a chemotherapy cycle. This recommendation is based upon limited data from patients with solid tumors receiving chemotherapy, suggesting that immunization on day 4 or 5 of a chemotherapy cycle is more immunogenic than on day 16 [22,23]. There have been conflicting results regarding the immunogenicity of immunization on the first day of the chemotherapy cycle, with one study showing poor immunogenicity [24] but another study showing good immunogenicity [25]. Annual immunization of all family members and other close contacts is also recommended. (See "Seasonal influenza vaccination in adults" and "Seasonal influenza in children: Prevention with vaccines" and "Infection control measures for prevention of seasonal influenza".)

Patients with acute leukemia undergoing induction chemotherapy are at greatest risk of morbidity and mortality associated with influenza [26]. Most infections in such patients are acquired nosocomially [26]. Reported seroconversion rates to the inactivated influenza vaccine in patients with cancer have ranged between 24 and 78 percent [27-29]; a two-dose regimen does not appear to improve the response [30,31]. In a 2012 meta-analysis, seroconversion and seroprotection rates following influenza vaccination in patients with cancer were approximately one-third of those observed in immunocompetent patients [32]. The likelihood of response is affected by the intensity and type of chemotherapy and the timing of vaccine administration in the chemotherapy cycle.

The anti-CD20 monoclonal antibody, rituximab, has become a standard part of the treatment of CD20-positive B cell lymphomas. Since this agent depletes normal B cells, there is concern that it will attenuate the response to vaccines. In a study of lymphoma patients who had received a rituximab-containing treatment regimen within the previous six months, none of 67 patients developed seroprotective titers following administration of an adjuvanted inactivated pandemic H1N1 influenza A vaccine [33]. In contrast, 42 of 51 healthy controls (82 percent) developed seroprotective titers following vaccination.

Although an intranasally administered live attenuated influenza vaccine (LAIV) exists, it is not recommended in immunocompromised individuals. LAIV is considered safe for healthy nonpregnant individuals between 2 and 49 years of age [2,21]. Either the inactivated influenza vaccine or LAIV can be used in household contacts and health care workers caring for patients with cancer; However, only the inactivated influenza vaccine should be used among contacts of HCT recipients within two months of transplant and of HCT recipients with graft-versus-host disease [21]. (See "Seasonal influenza vaccination in adults", section on 'Choice of vaccine formulation' and "Immunizations for health care providers", section on 'Recommendation' and "Immunizations in hematopoietic cell transplant candidates and recipients", section on 'Household contacts' and "Seasonal influenza vaccination in adults".)

Antiviral prophylaxis should be considered for those undergoing the most intense chemotherapy under certain circumstances, such as within the first 48 hours following an exposure in an unvaccinated individual or when there is a poor match between the vaccine and circulating viruses. Detailed recommendations regarding antiviral prophylaxis are presented separately. (See "Prevention of seasonal influenza with antiviral drugs in adults", section on 'Postexposure prophylaxis' and "Seasonal influenza in children: Prevention with antiviral drugs", section on 'Outpatient settings'.)

Human papillomavirus vaccine — Cancer patients with an indication for human papillomavirus (HPV) vaccination should be immunized, unless they have a known hypersensitivity to any part of the vaccine or to yeast. However, cancer patients may have a suboptimal antibody response and lower vaccine efficacy [34]. Patients with thrombocytopenia are at risk of developing a hematoma after the intramuscular injection of the vaccine. Indications for HPV vaccination are discussed separately. (See "Human papillomavirus vaccination".)

Hepatitis B vaccine — Cancer patients who request the hepatitis B vaccine (regardless of whether or not they have a risk factor for developing hepatitis B) and all unvaccinated cancer patients who have any risk factor for hepatitis B should receive the hepatitis B vaccine [35]. As with other vaccines, cancer patients and HCT recipients may have suboptimal response to the hepatitis B vaccine. Regimens that include doubling the standard antigen dose or administering additional doses may increase response rates but, given the limited data with these alternative regimens, this approach cannot be routinely recommended. Hepatitis B and hepatitis A vaccines may be coadministered to cancer patients. (See "Hepatitis B virus immunization in adults".)

Hepatitis A vaccine — Cancer patients who have any risk factors for developing hepatitis A should receive the hepatitis A vaccine, probably in combination with the hepatitis B vaccine since many of the risk factors for hepatitis A and B overlap. As above, vaccine efficacy may be compromised in cancer patients. (See "Hepatitis A virus infection: Treatment and prevention".)

COVID-19 vaccine — Patients with cancer are generally eligible for coronavirus disease 2019 (COVID-19) vaccination. Although the immunogenicity and efficacy of COVID-19 vaccines are uncertain in patients receiving chemotherapy and other immunomodulatory agents, the potential for benefit from vaccination likely outweighs these uncertainties for most. (See "COVID-19: Vaccines" and "COVID-19: Considerations in patients with cancer".)

ZOSTER VACCINE — The US Advisory Committee on Immunization Practices (ACIP) recommends vaccination against herpes zoster for immunocompetent individuals ≥50 years of age [36]. Although the US Food and Drug Administration has approved the recombinant zoster vaccine (RZV) for immunocompromised individuals who are ≥18 years of age [37], the ACIP has not issued recommendations for its use in moderately to highly immunocompromised hosts, such as patients with cancer.

For all patients, the RZV is preferred over the live attenuated zoster (ZVL) vaccine; ZVL is contraindicated in those who are receiving moderate- to high-dose immunosuppressive therapy, such as cancer chemotherapy. ZVL is no longer available in the United States. Detailed information and a description of the differences between the two vaccines is discussed elsewhere (see "Vaccination for the prevention of shingles (herpes zoster)"). Timing of vaccine administration relative to cancer treatment is discussed above. (See 'Timing of immunizations' above.)

Patients with hematologic malignancies and solid tumors are at increased risk of developing herpes zoster (shingles) [38]. The incidence varies by type of cancer and treatment. Patients with Hodgkin disease are at particularly high risk for developing zoster, with rates approaching 30 percent during illness or its treatment [39].

Vaccination with RZV has been shown to be effective in eliciting humoral and cell-mediated immune responses against herpes zoster in patients with solid and hematologic cancers. In a randomized trial of 262 patients ≥18 years of age with solid tumors who received RZV (given as two doses one to two months apart) or placebo either before or during chemotherapy, RZV was safe and immunogenic; both humoral and cell-mediated immune responses persisted one year after vaccination [40]. Although all patients receiving RZV developed humoral immune response, those who received the vaccine prior to initiation of chemotherapy had higher immune responses compared with those who received the vaccine during chemotherapy. In a randomized trial of 569 patients ≥18 years of age with hematologic malignancies who received RZV (given as two doses one to two months apart) versus placebo, 80.4 percent of the vaccinated group developed a humoral immune response to herpes zoster compared with 0.8 percent in the unvaccinated group [41]. The immune response persisted through 13 months of follow up. No difference in adverse events was detected between the two groups. There are insufficient data at this time to make a recommendation for repeat doses of RZV and there may eventually be different recommendations for patients with hematologic versus solid tumor malignancies.

The recommendation is that for individuals who received ZVL prior to the oncologic diagnosis and treatment, vaccination with RZV is recommended. It may be reasonable to wait until the patient has completed chemotherapy, providing that they are not on other moderate to high-dose immunosuppressive therapies. ZVL remains effective for older patients with cancer who were previously vaccinated. In a cohort study of individuals ≥60 years of age receiving myelosuppressive chemotherapy for solid tumors (4710 of whom had previously received ZVL and 16,766 of whom had not), the adjusted hazard ratio for herpes zoster among previously vaccinated individuals was 0.58 (95% CI 0.46-0.73) [42]. No vaccinated and six unvaccinated patients were hospitalized for herpes zoster.

The risk of ZVL in patients who have received immunosuppressive chemotherapy was illustrated by a fatal case of vaccine-derived disseminated varicella zoster infection reported in a 79-year-old man with chronic lymphocytic leukemia [43]. He had received ZVL six months after completing six cycles of fludarabine, cyclophosphamide, and rituximab; his remission status was not reported. The long-lasting immune effects of fludarabine and rituximab therapy as well as his advanced age may have predisposed this patient to disseminated infection.

LIVE-VIRUS VACCINES — Patients with cancer receiving chemotherapy should not receive live-virus vaccines (table 2) [2]. Recommendations regarding the timing of administration of live vaccines are discussed above. (See 'Timing of immunizations' above.)

Measles, mumps, and rubella vaccines — Cancer patients who are infected with measles have a high mortality rate [44]. Recommendations regarding the timing of administration of live vaccines are discussed above. (See 'Timing of immunizations' above.)

The 2013 United States Advisory Committee on Immunization Practices (ACIP) recommendations state that severely immunocompromised patients who have been exposed to measles should receive 400 mg/kg of intravenous immune globulin, regardless of vaccination or immunologic status [45]. Severely immunocompromised cancer patients include those receiving treatment for acute lymphoblastic leukemia until at least six months after completing therapy. (See "Measles, mumps, and rubella immunization in adults", section on 'Postexposure prophylaxis'.)

Varicella vaccine — Primary varicella is associated with high rates of morbidity and mortality in seronegative adults with cancer. Recommendations regarding the timing of administration of live vaccines are discussed above. (See 'Timing of immunizations' above.)

The varicella vaccine may be administered to susceptible household and other close contacts of cancer patients because transmission of varicella vaccine is rare [2,3]. If the household contact develops a rash after vaccination, the household contact should avoid direct contact with the immunocompromised cancer patient [46]. (See "Vaccination for the prevention of chickenpox (primary varicella infection)", section on 'Contacts of immunocompromised hosts'.)

One study evaluated the efficacy of the varicella vaccine in children in remission after treatment for leukemia [47]. The seroconversion rate was 88 and 98 percent after the first and second dose, respectively. There were few side effects, and breakthrough vaccine disease was effectively treated with acyclovir. Based upon this study, it is reasonable to immunize susceptible adult oncology patients with the varicella vaccine after completion of chemotherapy.

A case of disseminated fatal infection due to the vaccine strain of varicella was reported in an adult with recurrent diffuse large B cell lymphoma who was vaccinated four years following autologous hematopoietic cell transplantation (HCT); the patient had not received chemotherapy for several years but had new diffuse large B cell lymphoma in abdominal lymph nodes [48].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Immunizations in adults".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Beyond the Basics topic (see "Patient education: Vaccines for adults (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Prevention of infection is of paramount importance to the ever-increasing population of patients who have impaired immunity. Infection in these patients often results in excessive morbidity and mortality, and antimicrobial therapy is often less effective than in the unimpaired host. (See 'Introduction' above.)

●Although immunization appears to be an obvious way to prevent infection, many patients with impaired immunity are unable to mount a protective immune response to active vaccination. Furthermore, immunization with live-virus vaccines may result in unchecked proliferation of attenuated strains. (See 'Introduction' above.)

●All indicated vaccines should be given to adult cancer patients before initiation of chemotherapy, before therapy with other immunosuppressive drugs, and before radiation or splenectomy, when feasible. Indicated inactivated vaccines should be given ≥2 weeks prior to chemotherapy, and indicated live-virus vaccines should be given ≥4 weeks prior to chemotherapy. (See 'Timing of immunizations' above.)

●Patients with cancer receiving chemotherapy or other immunosuppressive therapy should not receive live vaccines and should generally not receive inactivated vaccines. 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. Patients with leukemia, lymphoma, or other malignancies whose disease is in remission, who have not received anti-B cell antibodies (eg, rituximab, alemtuzumab), and whose chemotherapy has been terminated for at least three months may receive live-virus vaccines, such as the vaccines for measles, mumps, rubella, and varicella according to age-specific recommendations. In patients who have received anti-B cell antibodies, administration of inactivated and live vaccines should be delayed for at least six months. (See 'Timing of immunizations' above.)

●The United States Advisory Committee on Immunization Practices immunization schedule for adults with medical conditions is presented in the following figure (figure 1). (See 'General approach' above.)