Immunizations in hematopoietic cell transplant candidates, recipients, and donors

INTRODUCTION — Hematopoietic cell transplant (HCT) candidates and recipients are highly susceptible to many typical and opportunistic infectious organisms due to their profoundly impaired immune system. Since antimicrobial therapy is typically less effective in this patient population than in the immunocompetent host, infections in these patients often results in excessive morbidity and mortality [1]. Strategies to prevent infection in this patient population includes the use of vaccines and/or passive immunization (ie, immune globulin) as well as pre-exposure and postexposure prophylaxis.

The approach and rationale for immunizing HCT candidates and recipients are reviewed here. This topic also discusses the approach and rationale for immunizing household contacts of HCT recipients and the limited role for HCT donor immunizations.

In the context of this topic, HCT recipients are defined as patients who are still considered immunocompromised due to their HCT. HCT recipients are no longer considered immunocompromised (and thus can resume immunization schedules as per the general population) once they are ≥2 years post-transplant, no longer have graft-versus-host disease (GVHD), and have not received any immunosuppressive therapy for at least six months.

Pre-exposure prophylaxis and other issues related to infections in HCT candidates and recipients is discussed elsewhere. (See "Evaluation for infection before hematopoietic cell transplantation" and "Prevention of infections in hematopoietic cell transplant recipients" and "Prophylaxis of invasive fungal infections in adult hematopoietic cell transplant recipients" and "Prevention of viral infections in hematopoietic cell transplant recipients" and "Overview of infections following hematopoietic cell transplantation".)

Issues related to immunizations in patients who have had or are waiting for a solid organ transplant (SOT), who have undergone chemotherapy for treatment of hematologic malignancies or solid tumors, or who have other immunocompromising conditions are also discussed elsewhere. (See "Immunizations in solid organ transplant candidates and recipients" and "Immunizations in adults with cancer" and "Immunizations in autoimmune inflammatory rheumatic disease in adults" and "Immunizations in persons with HIV".)

GENERAL PRINCIPLES — The general principles driving approach to immunization in hematopoietic cell transplant (HCT) candidates and recipients are based upon the underlying scientific principles of immunogenicity and the degree of immunosuppression and the risk of infection in this patient population. Surveys performed in Europe and the United States have shown that immunization practices after HCT vary widely [2,3].

●Degree of immunosuppression — The risk of acquiring infection and the inability to prevent infection by immunization are directly related to the patient's "net state of immunosuppression" (figure 1). The greater the degree of immunosuppression, the less likely the patient is to respond to immunization. Although vaccines may provide some benefit to the immunocompromised patient, an adequate response cannot be assumed.

The degree of immunosuppression after HCT varies with the type of underlying condition and type of transplant (table 1). Both types of HCT recipients initially have profound humoral and cell-mediated immunodeficiency but gradually recover to the point of capable functional B and T cell responses [4], although the immunosuppression associated with allogeneic HCT is generally more intense and lasts for a longer period of time [5-7].

•Allogeneic HCT – After allogeneic HCT, the immune system of the recipient is replaced by the immune system of the donor. Factors contributing to the patient's "net state of immunosuppression" are complex and include the conditioning regimen for HCT, the presence of graft-versus-host disease (GVHD), the immunosuppressive agents administered before and after transplantation, as well as the patient's underlying disease and comorbidities (table 1).

•Autologous HCT – Since there is no immunologic disparity between graft and host after autologous HCT, the factors contributing to the "net state of immunosuppression" are primarily the chemotherapy (both for the underlying malignancy as well as in preparation for the HCT), radiotherapy administered before transplantation, and the underlying disease itself (table 1).

●Risk of infection — Both autologous and allogeneic HCT recipients are at risk of developing infectious complications during the period of immune reconstitution. The risk for certain infectious organisms based on the time since transplant is presented in the following figures for recipients of allogeneic HCT (figure 2) and autologous HCT (figure 3). (See "Overview of infections following hematopoietic cell transplantation".)

●Principles of immunization and immunity — 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. Hence, we employ passive immunization and prophylactic antimicrobials to protect the patient during their most vulnerable time immediately post-transplant. The goal is to maintain protective immunity through this period of profound immunosuppression when the recipient is unable to respond to immunization by focusing on transferring, maintaining, and eventually eliciting protective immunity. (See "Prevention of infections in hematopoietic cell transplant recipients" and "Prophylaxis of invasive fungal infections in adult hematopoietic cell transplant recipients" and "Prevention of viral infections in hematopoietic cell transplant recipients".)

●Safety of vaccines – Inactivated vaccines are generally safe and acceptable in HCT candidates and recipients. Most live virus vaccines are avoided altogether during the first 24 months following HCT, as immunization with live virus vaccines may result in unchecked proliferation of attenuated strains. (See 'Live virus vaccines' below.)

PRE-TRANSPLANT — There is very limited data to help guide timing of vaccination in hematopoietic cell transplant (HCT) candidates. Prior to HCT, it is reasonable for HCT candidates to receive the vaccines that are indicated for all individuals based upon age (figure 4 and figure 5 and figure 6), comorbidities (figure 7), vaccination history, and exposure history [8]. However, although some HCT candidates who undergo reduced intensity conditioning regimens may maintain some protection from vaccinations, most HCT candidates are already immunocompromised and are unlikely to mount a substantial immune response to the vaccines. Additionally, all HCT candidates will require revaccination after their transplant, regardless of their vaccine status prior to transplant.

When vaccines are administered, inactivated vaccines should be administered ≥2 weeks prior to the initiation of the conditioning regimen. HCT candidates who are not immunocompromised can also receive live virus vaccines; live vaccines should be administered ≥4 weeks prior the initiation of the conditioning regimen. HCT candidates who are already immunocompromised (eg, underlying immunocompromising medical condition, chemotherapy) should generally avoid live virus vaccines.

Detail on COVID-19 vaccines and timing for HCT candidates is discussed separately. (See "COVID-19: Vaccines" and "COVID-19: Considerations in patients with cancer", section on 'COVID-19 vaccination'.)

Vaccination of adults with cancer is discussed in detail separately. (See "Immunizations in adults with cancer".)

POST-TRANSPLANT

Timing and administration of vaccines — The optimal timing of immunization following hematopoietic cell transplant (HCT) requires a balance between the ability to induce adequate immune responses, which increases over time, and the importance of providing protection during the highest risk period. As an example, the median time for developing invasive pneumococcal and Haemophilus influenzae type b (Hib) disease was about nine months after transplantation in one study [9].

The approach to immunization and timing in autologous HCT recipients (table 2) and allogeneic HCT recipients (table 3) is summarized in the tables.

In the context of this topic, HCT recipients are defined as patients who are still considered immunocompromised due to their HCT. HCT recipients are no longer considered immunocompromised (and thus can resume immunization schedules as per the general population) once they are ≥2 years post-transplant, no longer have graft-versus-host disease (GVHD), and are no longer receiving any immunosuppressive therapy for at least six months.

Specific recommendations for each vaccine are presented below. Most live virus vaccines are avoided altogether during the first 24 months following HCT. (See 'Live virus vaccines' below.)

Select circumstances may require alteration of the typical immunization schedule. Examples are provided below:

●Timing of vaccines may be delayed in certain circumstances when the patient is significantly immunocompromised, such as in the case of chronic GVHD. (See "Clinical manifestations, diagnosis, and grading of acute graft-versus-host disease" and "Treatment of chronic graft-versus-host disease".)

●Timing of vaccination in patients receiving intravenous immunoglobulin (IVIG) and other blood products is discussed in detail elsewhere. (See "Overview of intravenous immune globulin (IVIG) therapy", section on 'Vaccination of patients receiving IVIG'.)

●Patients who undergo a second HCT should re-initiate post-HCT vaccinations after their second HCT as the immunity obtained from vaccination after the first HCT has likely waned considerably [10].

Recommended non-live vaccines — The following vaccines are recommended for all HCT recipients. The timing for administration of each vaccine differs.

COVID-19 — We agree with recommendations from United States Centers for Disease Control and Prevention Advisory Committee on Immunization Practices (ACIP) that all HCT recipients ≥6 months of age should receive coronavirus disease 2019 (COVID-19) vaccination (table 2 and table 3) [11].

●Initial vaccination – All HCT recipients should undergo COVID-19 vaccination at least three months after transplantation, regardless of whether they were vaccinated prior to transplant. We typically administer a messenger ribonucleic acid (mRNA) vaccine when available, because there is more evidence on the efficacy and safety of this vaccine formulation in this population, including potential use of additional doses, to try to improve immunogenicity [12]. The mRNA vaccines are administered as a three-dose series in HCT recipients. Dosing intervals should follow the recommended schedule for each specific vaccine.

●Booster doses for individuals vaccinated after transplant – Patients who have already received a primary series post-transplant should receive additional doses as recommended by the ACIP [11]. Since immunocompromised individuals have a diminished response to vaccination, the United States Centers for Disease Control and Prevention (CDC) guidelines allow for additional doses of vaccine in immunocompromised patients, at clinician discretion [13]. Details on dosing are discussed elsewhere. (See "COVID-19: Vaccines", section on 'Immunocompromised individuals'.)

HCT recipients have a suboptimal immunogenic response after receiving a single dose of an mRNA vaccine [14,15]. Administration of additional doses of an mRNA vaccine increases the likelihood of patients achieving a protective antibody response to COVID-19 [16,17]. In an open-label study of 88 allogeneic HCT recipients who received two doses of the BNT162b2 mRNA vaccine, 59 percent of individuals had anti-SARS-CoV-2 immunoglobulin (Ig)G titers indicative of vaccine protection [14]. Receipt of systemic immunosuppressive agents within the past three months and an absolute lymphocyte count <1000 cells/microL were associated with suboptimal antibody response. There were no cases of symptomatic COVID-19 detected at 84 days of follow-up. In another study of 42 patients who received an allogeneic HCT at least three months previously, who did not achieve a protective antibody response after the second dose of BNT162b2 mRNA vaccine, and proceeded to receive a third dose, 48 percent developed a protective immunogenic response [16].

COVID-19 mRNA vaccines are considered safe in HCT recipients ≥3 months post-transplant. While there is very rare risk for myopericarditis in healthy adolescent and young adult patients that usually occurs after receiving the second dose of an mRNA vaccine close to the first dose, it is unknown whether patients receiving cardiotoxic chemotherapeutics (eg, anthracyclines) or additional mRNA vaccine doses have an increased risk for cardiotoxicity [18]; the risks of cardiac complications from true infection likely outweigh the very small risk from vaccination. For those concerned about the risks associated with mRNA vaccines, other vaccine formulations are reasonable alternatives (eg, protein subunit SARS-CoV-2 vaccine [Novavax]).

Further details on COVID-19 vaccines are discussed separately. (See "COVID-19: Vaccines".)

Streptococcus pneumoniae — Pneumococcal vaccination is important because HCT recipients are at increased risk for invasive disease from encapsulated bacteria such as Streptococcus pneumoniae [19-26].

●Vaccine administration – In accordance with the ACIP, we vaccinate all HCT recipients against S. pneumoniae [27]. We continue to administer the pneumococcal vaccines on the schedule recommended by the 2013 Infectious Diseases Society of America (IDSA) guideline for vaccination of the immunocompromised host [8]. Patients residing in countries outside of the United States should be vaccinated against S. pneumoniae according to their country's national guidelines.

•Initial three doses – We administer three doses of a pneumococcal conjugate vaccine at one-month intervals starting three to six months following transplantation (table 2 and table 3) [4,8]. The 20-valent pneumococcal conjugate vaccine (PCV20) is preferred because it covers the most serotypes, but the 15-valent pneumococcal conjugate vaccine (PCV15) or 13-valent pneumococcal conjugate vaccine (PCV13) are reasonable alternatives if PCV20 is not available (table 4).

•Fourth dose

-For patients without GVHD who received PCV-20 for the first three doses, we administer a fourth PCV20 dose at least six months after the third dose and at least 12 months after transplant.

-For patients without GVHD who received PCV-10, PCV-13, or PCV-15 for the first three doses, we administer PCV20 (if available) or PPSV23 at 12 months after transplant to help broaden the immune response to more pneumococcal serotypes [8].

-For patients with GVHD, we administer a fourth dose of a pneumococcal conjugate vaccine at 12 months following HCT instead of PPSV23 since such patients respond particularly poorly to polysaccharide antigens. We prefer to administer PCV20 (if available) to maximize immunogenicity against a broad variety of pneumococcal serotypes. If PCV20 is not available, PCV15 (or another pneumococcal conjugate vaccine formulation) is a reasonable alternative.

It is no longer recommended to perform serologic testing for pneumococcal serotypes after completing the pneumococcal vaccination series in all HCT recipients.

●Rationale and efficacy – Pneumococcal vaccination is important because HCT recipients are at increased risk for invasive disease from encapsulated bacteria such as Streptococcus pneumoniae [19-26]. The risk is higher for allogeneic than autologous transplant recipients [25], and it is highest among allogeneic transplant recipients with GVHD [21-23]. In one prospective survey, invasive pneumococcal infection occurred in 20.8 per 1000 with chronic GVHD, 8.23 per 1000 allogeneic HCT recipients, and 3.8 per 1000 autologous HCT recipients [28]. (See "Overview of infections following hematopoietic cell transplantation".)

Inducing immunity against pneumococcus is challenging in HCT recipients because the PPSV23 is poorly immunogenic in this population, whereas pneumococcal conjugate vaccines (eg, PCV13, PCV15, PCV20) are more immunogenic but cover fewer serotypes. In one open-label study, 251 allogeneic HCT recipients received three doses of PCV13 at one-month intervals starting three to six months post-transplant, a fourth dose six months later, and one dose of PPSV23 one month after that [29]. Geometric mean fold rises of IgG geometric mean concentrations increased significantly from baseline to one month after the third dose of PCV13 for all PCV13 serotypes but declined over the following six months. An increase in antibody titers was seen again one month after the fourth dose of PCV13. There was little change following PPSV23 administration. The fourth dose of PCV13 was associated with increased local and systemic reactogenicity, but the overall safety profile was considered acceptable. Newer pneumococcal conjugate vaccine formulations appear to be as effective and safe as the older ones. In a phase-3 randomized trial of 274 allogeneic HCT recipients, those who received PCV15 had comparable immune responses and similar safety profiles to those who received PCV13 [30].

Further discussion of pneumococcal vaccines is found elsewhere. (See "Pneumococcal vaccination in adults".)

Influenza — Influenza vaccination remains the primary method for preventing influenza.

●Administration of vaccine – We administer an inactivated formulation of the influenza vaccine to all HCT candidates and recipients ≥6 months of age every year. Vaccination should be given beginning six months following transplantation. If there is a community influenza outbreak, the vaccine can be given as early as four months following transplantation; in these situations, a second dose should be administered at least four weeks after the initial early dose to provide additional protection against influenza (table 2 and table 3) [4,8]. Individuals <9 years of age who have not previously been vaccinated against influenza should receive two doses of the influenza vaccine, approximately one month apart. The live attenuated (intranasal) formulation should not be given to HCT recipients. (See 'Live virus vaccines' below and "Seasonal influenza vaccination in adults" and "Seasonal influenza in children: Prevention with vaccines", section on 'Target groups'.)

●Adjunctive strategies to prevent influenza – Adjunctive strategies for protection of HCT recipients involve immunizing close contacts and hospital staff as well as chemoprophylaxis of HCT recipients in some cases. (See 'Household contacts' below and "Seasonal influenza vaccination in adults" and "Infection control measures for prevention of seasonal influenza" and "Seasonal influenza in adults: Role of antiviral prophylaxis for prevention" and "Seasonal influenza in children: Prevention with vaccines", section on 'Target groups' and "Prevention of viral infections in hematopoietic cell transplant recipients", section on 'Chemoprophylaxis' and "Seasonal influenza in children: Prevention with antiviral drugs".)

●Rationale and efficacy – Influenza A and B infections can be life-threatening in HCT recipients [31-34]. In one series, 5 to 6 percent of HCT recipients admitted with a respiratory illness had influenza and, in more than half, upper respiratory tract infection progressed to pneumonia (invasive influenza or secondary bacterial or fungal disease), resulting in a 50 percent mortality rate [34]. (See "Seasonal influenza in adults: Clinical manifestations and diagnosis".)

Vaccine-elicited antibody titers are lower early after HCT (during the first six months) and in patients with GVHD [35,36]. Nonetheless, some protection can be elicited. As an example, in a cohort study of 136 allogeneic HCT recipients, trivalent influenza vaccination was associated with a lower prevalence of influenza infection, slower progression to lower respiratory tract disease, and lower risk of hospitalization [37]. Compared with standard-dose trivalent inactivated vaccine, the high-dose vaccine elicited higher protective antibody titers in HCT recipients and was well tolerated except for injection-site reactions, which were mostly mild and resolved [38].

Timing of vaccine administration predicts the response. In one study, the response rate to influenza vaccine after HCT was zero if given in the first six months after transplant, 25 percent between months 6 and 24, and more than 60 percent after month 24 [39]. More recent data showed that influenza immunization at least six months after HCT was 80 percent effective in preventing influenza [40] and that influenza-specific T cell responses that might modify the course of infection could be elicited in patients vaccinated three to six months after HCT [41].

Tetanus, diphtheria, and pertussis — We agree with the 2013 IDSA guidelines for vaccination of the immunocompromised host to administer three doses of tetanus- and diphtheria-containing vaccine six months following HCT (table 2 and table 3) [8].

●Vaccine administration – We administer three doses of diphtheria, tetanus, and pertussis (DTaP) vaccine spaced one to three months apart starting six months following HCT [8,42]. For patients ≥7 years of age, an alternative schedule includes one dose of tetanus, diphtheria, and pertussis (Tdap) vaccine followed by either two doses of diphtheria and tetanus (DT) vaccine or two doses of tetanus and diphtheria (Td) vaccine.

DT contains full doses of both diphtheria toxoid and tetanus toxoid, whereas Td contains a full dose of tetanus toxoid and a reduced dose of diphtheria toxoid. In the United States, DT and DTaP are not approved by the US Food and Drug Administration (FDA) for individuals >6 years due to adverse effects [8]. However, a study in adult HCT recipients suggests that such individuals have a lower risk of adverse effects with DT administration compared with immunocompetent adults [43]. It is not known whether the immune response to Td is equivalent to the response to DT. There are also data suggesting that the response to Tdap is poor in autologous HCT recipients [44], suggesting that it should be used as a booster rather than as part of the primary series. For this reason, the IDSA states that a three-dose series of DTaP should be considered for initial vaccination following HCT regardless of patient age [8].

●Rationale – Tetanus and diphtheria are rare in resource-rich settings. However, tetanus remains common in resource-limited settings and sporadic cases continue to occur in resource-rich settings as well. Large epidemics of diphtheria have occurred in states of the former Soviet Union, and the disease remains endemic in some parts of the world. (See "Tetanus" and "Epidemiology and pathophysiology of diphtheria", section on 'Burden of disease'.)

The incidence of pertussis has been increasing in the United States and worldwide due largely to waning immunity among adolescents and adults. HCT recipients are particularly vulnerable to pertussis infection because of pulmonary damage due to chemotherapy and/or total body irradiation. In one study, only 13.5 percent of HCT recipients had protective titers against pertussis after transplantation and only 2 of the 28 patients developed a twofold or greater response to vaccination with Tdap [43]. (See "Pertussis infection: Epidemiology, microbiology, and pathogenesis", section on 'Epidemiology'.)

●Efficacy – A significant proportion of HCT recipients lack immunity to tetanus, diphtheria, and pertussis after transplantation [43-47]. Titers of both tetanus and diphtheria antibodies vary by age at transplantation, underlying diagnosis, dose intensity, duration of treatment before transplantation, and the transplantation conditioning regimen. Approximately 50 percent of allogeneic HCT recipients and 19 percent of autologous HCT recipients who had protective levels of tetanus antibody before transplantation become seronegative within one year of transplantation [45,46]. Only 36 percent of HCT recipients retain immunity to diphtheria [48].

Vaccination against tetanus, diphtheria, and pertussis is discussed in greater detail separately. (See "Diphtheria, tetanus, and pertussis immunization in children 6 weeks through 6 years of age" and "Diphtheria, tetanus, and pertussis immunization in children 7 through 18 years of age" and "Pertussis infection in adolescents and adults: Treatment and prevention", section on 'Vaccination' and "Tetanus-diphtheria toxoid vaccination in adults".)

Haemophilus influenzae — We administer three doses of Haemophilus influenzae type b (Hib) conjugate vaccine, each four weeks apart, to all HCT recipients, starting at 6 to 12 months following transplantation (table 2 and table 3) [4,8,42,49].

After the first six months following transplantation, HCT recipients are at increased risk for invasive disease from encapsulated bacteria, such as Haemophilus influenzae type b (Hib) [19,21,22,24,50]. The risk is higher for allogeneic than autologous transplant recipients [25], and it is highest among allogeneic transplant recipients with GVHD [21-23]. The incidence of Hib infections is not well established in HCT recipients, although fatal infections due to this pathogen are rare. (See "Overview of infections following hematopoietic cell transplantation".)

The increased susceptibility to encapsulated organisms is caused by low serum anticapsular antibody concentrations following transplantation [23,26]. In one study, for example, less than 30 percent of HCT recipients had protective antibodies against Hib one year after transplantation [50]. Immunization with all unconjugated polysaccharide vaccines (pneumococcus, Hib, and meningococcus) does not increase anticapsular polysaccharide antibody concentrations because HCT recipients respond poorly to T cell-independent polysaccharide antigens [26,51]. Fortunately, the polysaccharide-conjugate vaccine against H. influenzae is an effective alternative to the unconjugated vaccines and is well tolerated and immunogenic in HCT recipients [52-54].

Vaccination against H. influenzae is discussed in greater detail elsewhere. (See "Prevention of Haemophilus influenzae type b infection".)

Hepatitis B — Hepatitis B is a well-recognized cause of morbidity and mortality in transplant recipients. Hepatitis B vaccination is particularly important for HCT recipients who are positive for hepatitis B core antibody (HBcAb) because vaccination may reduce the risk of hepatitis B reactivation [4]. The risk of acquiring hepatitis B after transplantation remains low unless the recipient has well-known risk factors, such as receiving hemodialysis.

●Administration – We administer a three-dose series of hepatitis B vaccine 6 to 12 months following HCT (table 2 and table 3); we prefer to wait until 12 months when possible to optimize immunity from the vaccine [8]. Dosing intervals depends on the specific hepatitis B vaccine formulation used. There is no preference for one hepatitis B vaccine formulation over another. (See "Hepatitis B virus immunization in adults" and "Hepatitis B virus immunization in infants, children, and adolescents".)

●Follow up serologic testing – We test hepatitis B serology ≥1 month following the third dose to assess the response to vaccine [4]. In patients with anti-HBs concentrations <10 milli-international units/mL (known as non-responders), we administer a second three-dose series. For adolescents and adults who did not respond to the first vaccination series, we administer either a high dose of the vaccine (40 mcg) or the adjuvanted vaccine (Heplisav) to optimize immunogenicity. For children, either the standard dose or the high dose can be given [4]. In those with an obvious reason for a poor response, such as chronic GVHD, it is preferable to wait until the underlying issue has improved. (See "Hepatitis B virus immunization in adults", section on 'Postvaccination testing' and "Hepatitis B virus immunization in infants, children, and adolescents", section on 'Postvaccination serology'.)

●Efficacy – Autologous HCT recipients immunized close to transplantation and allogeneic recipients immunized after transplantation with recombinant hepatitis B vaccine had variable and suboptimal responses [55,56]. In a study of 292 allogeneic transplant recipients not receiving immunosuppression and considered immune competent, 64 percent seroconverted following immunization with recombinant hepatitis B vaccine [57]. In a multivariate analysis, factors significantly associated with a poor immunologic response included age >18 years and previous chronic GVHD.

Recombinant herpes zoster vaccine — We vaccinate against herpes zoster (shingles) in HCT recipients ≥18 years of age with recombinant (nonlive) zoster vaccine (RZV) [58]. Timing of administration depends on whether the patient received an autologous or an allogeneic HCT. The live attenuated zoster vaccine (ZVL) is not recommended while they are immunocompromised. Further information on the differences between the two zoster vaccines is discussed separately. (See "Vaccination for the prevention of shingles (herpes zoster)".)

●Autologous HCT recipients – In autologous HCT recipients, we administer the first dose 50 to 70 days following transplant and the second dose one to two months later (table 2) [59].

Our recommendations are based on the results of a large international multicenter observer-blinded phase III trial in which 1846 adult autologous HCT recipients were randomly assigned to receive two doses of RZV or placebo 50 to 70 days following HCT and one to two months later [60]. After a median of 21 months of follow-up, the vaccinated group had a lower incidence of herpes zoster compared with the placebo group (incidence 30 and 94 per 1000 person-years, respectively; incidence rate ratio [IRR] 0.32, 95% CI 0.22-0.44; 68.2 percent vaccine efficacy). Vaccination was also associated with a reduction in postherpetic neuralgia (IRR 0.11, 95% CI 0.00-0.78), other herpes zoster-associated complications (IRR 0.22, 95% CI 0.04-0.81), herpes zoster-associated hospitalization (hazard ratio [HR] 0.15, 95% CI 0.03-0.68), and duration of severe worst herpes zoster-associated pain (HR 0.62, 95% CI 0.42-0.89). Injection site reactions were reported in 86 percent of vaccine recipients and 10 percent of placebo recipients. Unsolicited and serious adverse effects, potentially immune-mediated diseases, and underlying disease relapses were similar between groups. Because of concerns of immunogenicity from the novel adjuvant contained in RZV, development of immune-mediated diseases was monitored in the trial. During the year following the second dose, 13 vaccine recipients and 8 placebo recipients reported at least one potentially immune-mediated disease; this difference was not statistically significant. The most frequently reported events in vaccine recipients were psoriasis and interstitial lung disease (in two vaccine recipients for each event).

●Allogeneic HCT recipients – Hematopoietic transplant programs at academic centers vary with regard to timing of administering the RZV to allogeneic HCT recipients. We suggest the recombinant zoster vaccine when the patient meets the following criteria (table 3) [61]:

•At least 12 months has passed since HCT

•Off immunosuppressive therapy for at least 8 months

•No recent GVHD flares

The second dose should be administered two to six months after the first dose. We generally try to administer the first dose of RZV at least a month prior to cessation of antiviral prophylaxis therapy [49]. Since data on efficacy and safety of RZV in allogeneic HCT recipients are scarce, antiviral prophylaxis (eg, acyclovir) is used to prevent herpes zoster infection early after transplant. (See "Prevention of viral infections in hematopoietic cell transplant recipients".).

Data on the efficacy and safety of RZV in allogeneic HCT recipients are scarce. In one single-center prospective cohort study of allogeneic HCT recipients on antiviral prophylaxis (30 percent with acute GVHD at time of vaccination) who received the first dose of RZV between 9 to 24 months post-HCT and the second dose at least two months later, there was no difference in GVHD incidence post-vaccination compared with the incidence rate in unvaccinated HCT recipients [62]. Of the 34 patients who discontinued antiviral prophylaxis during the study follow-up, four developed HZ with one fatal case. Although the data are promising, further studies on safety and efficacy are needed prior to recommending RZV vaccination earlier than two years post-HCT.

Poliovirus — We administer the inactivated poliovirus vaccine to all HCT recipients. The vaccine is given as a three-dose series and should be initiated 6 to 12 months following transplantation (table 2 and table 3) [4,8]. The doses can be administered one to three months apart [42]. The live oral poliovirus vaccine should not be given to HCT recipients, their household contacts, or their health care providers. HCT recipients should be counseled of the risk of exposure to poliovirus via oral-fecal route during travel to areas where the live oral polio vaccine is still given, as it could revert back to wild type-like virus and cause vaccine-associated paralytic poliomyelitis [63]. Vaccination against poliovirus is discussed in greater detail elsewhere. (See "Poliovirus vaccination".)

Postvaccination serology should be checked approximately four to five years after vaccination for those at higher risk of exposure (eg, residing in or traveling to areas with poliovirus transmission). If negative, we repeat the three-dose vaccination series. Approximately 33 percent of allogeneic HCT recipients lose protective antibody to all three poliovirus vaccine types two to three years after transplantation [64], whereas 20 percent of autologous transplant recipients become seronegative to at least one poliovirus vaccine type within the first transplant year [65]. In different studies, the inactivated poliovirus vaccine was moderately to highly immunogenic among HCT recipients [64,66].

Vaccines for select HCT recipients — The following vaccines are only recommended for certain subpopulations of HCT recipients, based on age and/or other risk factors.

Non-live vaccines — Indications for the following vaccines are the same as for general population. They should all be given starting at six months post-transplant (table 2 and table 3).

●Hepatitis A – Patients with chronic liver disease (eg, GVHD, concurrent infection with other hepatitis viruses) and those planning travel to endemic regions may benefit from hepatitis A vaccine [67]. A small study in allogenic stem cell transplant recipients showed a markedly diminished response to two doses of vaccine at only 33 percent seroconversion [68], with the first dose at a median of 333 days after HCT. No booster effect was seen in those with prior immunity. (See "Hepatitis A virus infection: Treatment and prevention", section on 'Indications'.)

●Human papillomavirus – Limited data suggest the quadrivalent vaccine is immunogenic following transplant [69]. Human papillomavirus infection (HPV) vaccine is recommended for individuals aged 9 to 26 years. (See "Human papillomavirus vaccination", section on 'Indications and age range'.)

●Respiratory syncytial virus (RSV) – HCT patients are at high risk for respiratory syncytial virus (RSV) disease. In 2023, two RSV vaccines were approved for people 60 years of age and over, and the ACIP made a recommendation for them to be given under shared clinical decision making (table 5) [70]. In accordance with the ACIP, we offer the RSV vaccine to all HCT recipients who are ≥60 years of age at least 6 months after transplantation [71]. Although not studied in HCT recipients, given the high risk of disease, we believe the benefits outweigh the potential risks. Vaccination against RSV is discussed in greater detail elsewhere. (See "Respiratory syncytial virus infection in adults", section on 'Vaccination'.)

●Neisseria meningitidis — In accordance with the IDSA guidelines on immunization of HCT recipients, we administer meningococcal vaccines to those at increased risk for meningococcal disease, based on age and comorbidities as for the general population. Other guidelines, including the United Kingdom guidelines [10] and Australia guidelines [72] recommend two doses of the MenB vaccine two months apart starting at six months post-transplant and two doses of the meningococcal conjugate vaccine (MenACWY) two months apart, starting six [72] to eight [10] months post-transplant. If immunization against all five meningococcal groups is indicated, the pentavalent meningococcal conjugate vaccine (MenABCWY) can be administered, if available.

Although there have been few studies evaluating the immunogenicity of meningococcal vaccination in HCT recipients [73,74], it is plausible that the conjugate vaccine is more immunogenic than the polysaccharide vaccine in this population since polysaccharide vaccines are known to generally be less immunogenic in HCT recipients than conjugate vaccines. Meningococcal vaccination (including indications, schedules, and need for revaccination) are outline in the following tables (table 6 and table 7) and discussed in detail separately. (See "Meningococcal vaccination in children and adults", section on 'Immunization of persons at increased risk'.)

●Mpox virus — HCT recipients at risk for mpox exposure (eg, males who have sex with males and have multiple sex partners or have been diagnosed with an sexually transmitted infection [STI] in the past six months) should receive the live, nonreplicating, modified vaccinia Ankara (MVA) vaccine, which has been shown to be safe for immunocompromised people. The replication-competent smallpox vaccine (ACAM2000) is contraindicated in HCT recipients. (See "Treatment and prevention of mpox (monkeypox)", section on 'Pre-exposure prophylaxis with orthopoxvirus vaccines'.)

Live virus vaccines — Live virus vaccines are generally avoided in HCT recipients, particularly during the first two years post-transplant and in HCT recipients with active GVHD and/or ongoing immunosuppression [8]. In certain circumstances, certain live vaccines (measles, mumps, and rubella [MMR]; varicella) may be indicated. A list of live vaccines is provided in the following table (table 8).

Measles, mumps, and rubella — Although measles, mumps, and rubella are vaccine-preventable diseases, outbreaks of measles and mumps continue to occur due to incomplete vaccination of the population. Measles can cause severe disease in immunocompromised patients as evidenced by an epidemic in HCT recipients that occurred in Brazil [75]. In addition, protection against rubella is important for female patients who may become pregnant. (See "Measles: Clinical manifestations, diagnosis, treatment, and prevention" and "Mumps" and "Rubella".)

●Administration – Optimizing immunity to measles, mumps, and rubella in HCT populations includes checking serology in select patients and immunizing those who are seronegative at a safe interval after transplant [4]:

•Check serology in select patients – Titers for measles, mumps, and rubella should be checked 24 months after HCT in:

-Pediatric patients

-Adults who received the MMR vaccine while immunosuppressed or within eight weeks prior to the initiation of immunosuppression

-Patients who may become pregnant

Patients who have received intravenous immunoglobulin (IVIG) in the past 12 months may have false positive titers.

For those who were vaccinated prior to transplant, antibody titers to measles, mumps, and rubella decrease over time in HCT recipients [76-78]. In one report, for example, 24, 49, and 58 percent of allogeneic HCT recipients had lost antibody to measles, mumps, and rubella, respectively, one to two years after transplantation [76]. Those who had natural infection are much less likely to become seronegative after transplant than those who were previously immunized with MMR.

•Immunize seronegative patients – We administer a two-dose series of the MMR vaccine to all measles and rubella seronegative pediatric and adult HCT recipients who meet all of the following criteria (table 2 and table 3) [4,8]:

-24 months has passed since transplantation

-Recipient does not have active GVHD

-Recipient is not receiving any immunosuppression

-Last dose of IVIG was administered more than 8 to 11 months ago

●Efficacy and safety – MMR appears to be safe and effective in both autologous and allogeneic HCT recipients [52,76,79,80]. In a study of 38 pediatric autologous or allogeneic HCT recipients, all patients developed protective antibodies to measles following vaccination [52]. A survey of 129 adult HCT recipients (75 autologous and 54 allogeneic) who were vaccinated 300 to 729 days (median, 718 days) after HCT, found only one significant reaction (centrifugal maculopapular rash, confirmed to be from vaccine strain rubella in a patient who underwent allogeneic HCT 542 days before vaccination); 39 (30 percent) of these were vaccinated earlier than 23 months post-transplant. Although MMR is safe for HCT recipients who are at least two years out from transplant and are not receiving immunosuppression, very rare cases of vaccine-associated measles among HCT recipients have been reported [81]. Furthermore, a study from Canada showed that MMR was contraindicated in a large proportion of patients; 80 percent of autologous HCT and 45 percent of allogeneic HCT recipients were on a contraindicated medication two years after transplant [82].

Vaccination against measles, mumps, and rubella is discussed in greater detail elsewhere. (See "Measles, mumps, and rubella immunization in infants, children, and adolescents" and "Measles, mumps, and rubella immunization in adults".)

Varicella — The varicella vaccine is a live attenuated vaccine that prevents chickenpox [4].

•Administration – Optimizing immunity to varicella in HCT populations includes checking serology in select patients and immunizing those who are seronegative at a safe interval after transplant [8,83]:

•Check serology in select patients – Varicella serology should be checked at least 24 months after HCT in:

-Pediatric patients (regardless of whether they received a varicella vaccine prior to transplant)

-Adults who did not receive the RZV vaccine post-transplant

Patients who have received IVIG in the past 12 months may have false positive titers.

•Immunize seronegative patients – In accordance with the Infectious Diseases Society of America (IDSA), we administer a two-dose series of the varicella vaccine to all seronegative patients who meet all of the following criteria [8,84]:

-24 months has passed since transplantation

-Recipient does not have active GVHD

-Recipient is not receiving any immunosuppression

-Last dose of IVIG was administered more than 8 to 11 months ago

Dosing schedule for children (figure 4 and figure 5) and adults (figure 6) is similar to the general population.

The live attenuated zoster vaccine is not recommended, due to its much higher viral titers compared with varicella vaccine. Although the RSV vaccine could theoretically provide protection against varicella, there are no clinical data to demonstrate its efficacy in this setting and the United States Center for Disease Control and Prevention (CDC) does not recommend RSV vaccine for those who are non-varicella immune as a way to protect against varicella.

●Efficacy and safety – The safety and efficacy of live attenuated varicella vaccine, either before or after transplantation, are not well established. The live attenuated varicella vaccine was evaluated in 15 pediatric HCT recipients immunized 12 to 23 months after autologous or allogeneic transplant [85]. The vaccine was well tolerated and humoral immune responses were elicited in eight of nine patients, with persistence of responses in six patients after two years.

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 with the live attenuated varicella vaccine four years following autologous HCT; the patient had not received chemotherapy for several years but had new diffuse large B cell lymphoma in abdominal lymph nodes [86]. Death from the vaccine strain of varicella is extremely rare.

Vaccination against varicella is discussed in greater detail elsewhere. (See "Vaccination for the prevention of chickenpox (primary varicella infection)".)

Contraindicated vaccines — Some live virus vaccines are contraindicated in HCT due to safety concerns. The following vaccines are contraindicated in HCT recipients: Bacillus Calmette-Guérin vaccine, oral poliovirus vaccine, intranasal influenza vaccine, live cholera vaccine, live replication-competent smallpox/mpox vaccine (ACAM2000), oral typhoid vaccine, live herpes zoster vaccine, yellow fever vaccine, chikungunya vaccine (VAL1553), and rotavirus vaccine [4,8].

The live virus vaccines that are indicated following HCT (eg, MMR; varicella) must be given only to those who meet specific criteria for timing and/or immune function. (See 'Measles, mumps, and rubella' above and 'Varicella' above.)

Travel-related vaccines — Certain vaccines (rabies, tick-borne encephalitis, inactivated Japanese encephalitis, yellow fever) can be considered for travelers to endemic areas or for those at increased risk of exposure [4]. However, there are few data regarding the safety and efficacy of these vaccines in HCT recipients and the decision of whether to administer them should be based upon the individual's risk of infection and the potential adverse effects. Of these vaccines, only the yellow fever vaccine is a live virus vaccine; it should only be given to HCT recipients who underwent transplantation >24 months earlier, do not have active GVHD, and are not receiving immunosuppression.

Immunizations in immunocompromised travelers are discussed in detail separately; the use of the different vaccines in HCT recipients must be considered in relation to the issues described in this topic. (See "Travel advice for immunocompromised hosts".)

Passive immunization for pre/post exposure — Passive immunization involves administering antibodies against an infectious organism to the patient without needing to induce a response from the patient's intrinsic immune system. Passive immunization is helpful in protecting a patient from infections while their immune system cannot mount an appropriate immune response to vaccines.

Respiratory syncytial virus prophylaxis — Respiratory syncytial virus (RSV) is a serious cause of pneumonitis in HCT recipients that tends to occur in outbreaks; mortality rates are between 15 and 70 percent in cohorts with and without treatment [87-91]. Passive immunization for RSV is limited to young children under the age of 4 years. It should not be necessary to use the two monoclonal antibodies in conjunction with each other in the same RSV season. (See "Respiratory syncytial virus infection: Prevention in infants and children", section on 'Immunoprophylaxis'.)

●Nirsevimab – Nirsevimab is recommended for infants aged <8 months born during or entering their first RSV season (November through April in the northern hemisphere) and for infants and children aged 8 to 19 months who are at increased risk of severe RSV disease and entering their second RSV season. Nirsevimab has not been studied in older children or adults.

●Palivizumab – Palivizumab is a humanized monoclonal antibody against the RSV F glycoprotein that is used by some HCT centers in HCT recipients <4 years of age as prophylaxis monthly during RSV season (November through April in the northern hemisphere) to prevent primary RSV pneumonitis [4], although this practice is not supported by clinical trials.

Varicella exposure — Varicella-seronegative HCT candidates undergoing conditioning for HCT and HCT recipients who underwent transplant within the previous 24 months, have chronic GVHD, or continue to require immunosuppression should be given varicella-zoster immune globulin (VariZIG) within 10 days (and ideally within 4 days) of close or household contact with a person with either chickenpox or shingles [4,92]. Close contact for adults is defined as continuous household contact, hospital contact in the same two- to four-bed room, or prolonged (more than five minutes) of face-to-face or same-room contact with an infectious person. If VariZIG is not available, postexposure valacyclovir should be given [4].

Details regarding formulation and dosing of VariZIG and antivirals are discussed separately. (See "Post-exposure prophylaxis against varicella-zoster virus infection" and "Prevention of viral infections in hematopoietic cell transplant recipients", section on 'VZV postexposure prophylaxis'.)

IVIG following hepatitis A exposure — Hepatitis A-susceptible HCT recipients (figure 8) who anticipate possible exposure to hepatitis A (eg, during travel to endemic regions, community outbreak) or who have a known exposure should receive IVIG, given the likely poor response to hepatitis A vaccine. Those already getting IVIG do not need additional doses of immune globulin [4,67]. (See "Hepatitis A virus infection: Treatment and prevention", section on 'Passive immunization'.)

IVIG following measles exposure — The United States Advisory Committee on Immunization Practices (ACIP) recommendations state that severely immunocompromised patients exposed to measles should receive intravenous immunoglobulin at a dose of 400 mg/kg regardless of vaccination or immunologic status [93]. This includes all HCT recipients who do not meet criteria for measles vaccination (eg, HCT within the past 24 months, on immunosuppressive therapy, has active GVHD, or received IVIG in the past 8 to 11 months). (See "Measles, mumps, and rubella immunization in adults", section on 'Post-exposure prophylaxis'.)

IVIG for other indications — Although the rationale for considering passive antibody immunotherapy may be clear, the cost-effectiveness of using immune globulin preparations for the prevention of infections other than varicella, hepatitis A, and measles continues to be intensely debated and investigated. The possible use of intravenous immunoglobulin and cytomegalovirus-specific immune globulin are discussed elsewhere. (See "Prevention of infections in hematopoietic cell transplant recipients", section on 'Intravenous immune globulin'.)

HOUSEHOLD CONTACTS — Household contacts should receive recommended routine vaccinations (figure 4 and figure 5 and figure 6 and figure 7). Household contacts with an indication for live vaccines should ideally receive them before the hematopoietic cell transplant (HCT) candidate undergoes transplantation provided there are no contraindications. (See "Standard immunizations for nonpregnant adults" and "Standard immunizations for children and adolescents: Overview", section on 'Routine schedule'.)

Under some circumstances, a household member of a HCT recipient may have received a live attenuated vaccine. The following precautions should be followed for preventing possible transmission of the attenuated vaccine virus to the HCT recipient when this situation arises:

●Influenza vaccine – Annual influenza vaccination is recommended for all family members and close or household contacts ≥6 months of age. Only the inactivated influenza vaccines (IIV) should be used among contacts of HCT recipients within a few months of transplant, after which time either IIV or the live attenuated influenza vaccine (LAIV) may be given to contacts of HCT recipients. Contacts who can avoid direct contact with HCT recipient for seven days after receiving the LAIV can receive the LAIV vaccine [8,94]. (See "Seasonal influenza vaccination in adults" and "Seasonal influenza in children: Prevention with vaccines", section on 'Target groups'.)

●Rotavirus vaccine – Two formulations of rotavirus vaccine, RV1 and RV5, are available. Both are live attenuated vaccines and are used in infants. Rotavirus vaccine should be given to infants who are household contacts of HCT recipients according to age-based recommendations [8]. (See "Rotavirus vaccines for infants", section on 'Routine schedule'.)

Although no cases of transmission of the attenuated vaccine virus have been reported, HCT recipients should avoid handling diapers of vaccinees for four weeks following vaccination [4,8]. When this is not possible, HCT recipients should adhere to strict hand hygiene practices after contact with the vaccinee's feces. Some HCT units prohibit infants who have received the rotavirus vaccine within the previous two to four weeks from visiting the HCT unit. (See "Rotavirus vaccines for infants", section on 'Shedding and transmission of vaccine virus'.)

●Varicella vaccine – Transmission of the live attenuated varicella vaccine virus has been reported very rarely [83]. Household members who have not had varicella infection should receive the varicella vaccine to protect the HCT recipient from potential exposure to wild-type virus, ideally before HCT has occurred [4,8]. Individuals who develop a varicella-like rash within one month of vaccination should be prohibited from visiting the HCT unit and should avoid close contact with the HCT recipient in the home setting. (See "Vaccination for the prevention of chickenpox (primary varicella infection)", section on 'Contacts of immunocompromised hosts'.)

●Measles, mumps, and rubella vaccine – Household members should receive the measles, mumps, and rubella (MMR) vaccine as indicated by age [4,8]. Individuals who develop a fever and/or rash following vaccination should be prohibited from visiting the HCT until signs and symptoms have resolved and should avoid close contact with the HCT recipient in the home setting. (See "Measles, mumps, and rubella immunization in adults" and "Standard immunizations for children and adolescents: Overview", section on 'Routine schedule'.)

●Mpox vaccine – All household contacts with an indication for mpox vaccination should receive the live, non-replicated modified vaccinia Ankara (MVA) vaccine. If a household member inadvertently receives the live, replicating ACAM2000 vaccine, the household member should keep the vaccination site covered and avoid contact (eg, direct skin-to-skin contact, sharing of blankets and towels, or swimming in same body of water) with the HCT recipient until the injection site lesion has completely healed and scab has fallen off to form a scar (generally a couple of weeks) [95]. (See "Vaccines to prevent smallpox, mpox (monkeypox), and other orthopoxviruses", section on 'Contraindications and precautions'.)

●Poliovirus vaccine – All household contacts with an indication for poliovirus vaccination should receive the inactivated poliovirus vaccine rather than the oral formulation, which is a live attenuated vaccine [4]. The oral (live) polio vaccine is no longer available in the United States. If a household member inadvertently receives the oral formulation, close contact between the household member and the HCT recipient should be avoided for four to six weeks. If avoidance of close contact is not possible, then the HCT recipient should practice stringent hand hygiene after contact with the feces of the vaccinee (eg, after changing a diaper) and avoid contact with saliva from the vaccinee, including not sharing food or eating utensils. Infants and children who have recently received the oral poliovirus vaccine should not visit the HCT unit for four to six weeks after receipt of the vaccine. (See "Poliovirus vaccination".)

●Zoster vaccine – All household contacts with an indication for herpes zoster vaccination should receive the non-live recombinant herpes zoster vaccine (RZV) rather than the live herpes zoster vaccine (ZVL) [8].

Although no cases of transmission of the live-attenuated vaccine (ZVL) virus have been reported, HCT centers should prohibit visitors who develop a varicella- or zoster-like rash following vaccination with the live-attenuated ZVL vaccine from visiting. If a household member develops such a rash after vaccination with ZVL, he or she should avoid close contact with the HCT recipient and should keep the rash covered. Management of HCT recipients who have been exposed to an individual with a zoster-like rash is discussed elsewhere. (See 'Varicella exposure' above and "Vaccination for the prevention of shingles (herpes zoster)".)

●Travel vaccines – Household contacts may receive the yellow fever vaccine and the oral typhoid vaccine if indicated for travel. (See "Immunizations for travel".)

LIMITED ROLE FOR DONOR IMMUNIZATION — Donor vaccination prior to stem cell harvest is a proposed approach to protecting hematopoietic cell transplant (HCT) recipients from vaccine-preventable disease early after transplant before the HCT recipient can achieve an adequate immune response to immunizations. We agree with the 2013 Infectious Diseases Society of America (IDSA) guidelines that recommend against vaccinating the donor solely for the benefit of the recipient due to practical and ethical challenges with this approach [8]. However, donor immunization can be done prior to stem cell harvesting when the donor is related to the recipient and agrees to being vaccinated in order to enhance the immune responses of the recipient [4].

The possible benefit to HCT recipients of vaccinating donors has been shown in studies with diphtheria and tetanus toxoid vaccines, Haemophilus influenzae B conjugate vaccine, pneumococcal conjugate vaccine, and hepatitis B vaccine [96-102]. In one report, for example, donors immunized with tetanus toxoid shortly before stem cell collection transferred a larger and more diverse tetanus toxoid-specific T cell repertoire to the recipient, indicating that donor immunization allows adoptive transfer of both B cells actively synthesizing antibody as well as antigen-specific T cells [98]. In another example, donor immunization with Hib conjugate vaccine resulted in significantly higher antibody concentrations in recipients of non-T cell-depleted allogeneic transplants as early as three months post-transplant compared with recipients of unimmunized donors [99]. In a randomized study of 65 HCT recipients, those whose donors were assigned to receive a dose of the 7-valent pneumococcal conjugate vaccine (PCV7) had a much higher rate of protective antibody concentrations to all seven serotypes after the first PCV7 vaccine dose at 3 months post-transplant compared to those whose donors received no vaccine before transplantation (67 versus 36 percent; p = 0.05) [101]. However, after all HCT recipients received all three doses of PCV7, both groups had more than 60 percent had protective antibody concentrations to all seven serotypes. Although these strategies may be effective, it is unclear whether they are more cost-effective than vaccinating HCT recipients post-transplant.

There are also case reports of attempts to clear chronically infected HCT recipients by immunizing the donor with hepatitis B vaccine and immunizing the recipient with hepatitis B vaccine in the early post-transplant period [55,103]. However, there are not enough data to support this practice in the clinical setting.

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 hematopoietic cell transplant recipients".)

SUMMARY AND RECOMMENDATIONS

●Pre-transplant vaccinations – Prior to hematopoietic cell transplant (HCT), it is reasonable for HCT candidates to receive the vaccines that are indicated for all individuals based upon age (figure 4 and figure 5 and figure 6), comorbidities (figure 7), vaccination history, and exposure history. All HCT candidates will require revaccination after their transplant, regardless of their vaccine status prior to transplant. (See 'Pre-transplant' above.)

●Post-transplant vaccinations

•Timing of vaccination − Following transplantation, HCT recipients typically lose immunity to pathogens against which they were previously immunized. Thus, HCT recipients should be immunized against a number of pathogens once they are likely to mount an immune response. Live virus vaccines are avoided altogether during the first 24 months following HCT. (See 'Timing and administration of vaccines' above.)

•Vaccines recommended for all HCT recipients – We vaccinate all HCT recipients against COVID-19, S. pneumoniae, influenza, tetanus, diphtheria, pertussis, haemophilus influenzae, hepatitis B, herpes zoster, and poliovirus. Suggested timing of vaccination is presented in the tables for autologous (table 2) and allogeneic (table 3) HCT recipients. (See 'Recommended non-live vaccines' above.)

•Vaccines recommended for select HCT recipients – Certain patients will benefit from vaccination against additional pathogens, such as hepatitis A, N. meningitidis, respiratory syncytial virus (RSV), mpox, human papillomavirus (HPV), measles, mumps, rubella, and/or varicella. Indications for and timing of these vaccines are outlined in the tables for autologous (table 2) and allogeneic (table 3) HCT recipients. (See 'Vaccines for select HCT recipients' above.)

●Role of passive immunization − Passive immunization is indicated in nonimmune HCT recipients under certain circumstances, such as following exposure to an individual with varicella, measles, or hepatitis A infection. (See 'Passive immunization for pre/post exposure' above.)

●Vaccination of household contacts − Household contacts should receive recommended routine vaccinations. (See 'Household contacts' above.)