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Prevention of infections in hematopoietic cell transplant recipients

Prevention of infections in hematopoietic cell transplant recipients
Author:
John R Wingard, MD
Section Editor:
Eric Bow, MD
Deputy Editor:
Milana Bogorodskaya, MD
Literature review current through: Jan 2024.
This topic last updated: Dec 01, 2023.

INTRODUCTION — Allogeneic hematopoietic cell transplant (HCT) recipients are at increased risk for a variety of infections based upon their degree of immunosuppression and exposures. Autologous HCT recipients are also at increased risk for infection, although to a lesser degree than those who have undergone allogeneic HCT.

The term "hematopoietic cell transplantation" will be used throughout this topic review as a general term to cover transplantation of hematopoietic cells from any source (eg, bone marrow, peripheral blood, umbilical cord blood). (See "Hematopoietic cell transplantation (HCT): Sources of hematopoietic stem/progenitor cells".)

Patients can develop a range of bacterial, fungal, viral, and/or parasitic infections following HCT. Infection in HCT recipients is associated with high morbidity and mortality. Thus, prevention of infection is a major goal, which involves determination of risk, careful selection of donors, prophylactic and/or pre-emptive antimicrobial therapy, immunization, and additional measures (eg, infection control).

The prevention of certain infections in HCT recipients will be discussed here; prophylaxis of bacterial infections, invasive fungal infections, and viral infections are discussed in greater detail separately. The evaluation for infection before HCT and an overview of infections following HCT are also presented separately. (See "Prophylaxis of infection during chemotherapy-induced neutropenia in high-risk adults" and "Prophylaxis of invasive fungal infections in adult hematopoietic cell transplant recipients" and "Prevention of viral infections in hematopoietic cell transplant recipients" and "Evaluation for infection before hematopoietic cell transplantation" and "Overview of infections following hematopoietic cell transplantation".)

EVALUATION BEFORE HCT — The pretransplantation evaluation is designed to prevent posttransplant infections by excluding unsuitable donors and defining specific infection control policies and antimicrobial prophylaxis and therapy, which will be necessary after transplantation. Laboratory testing for evidence of past infectious exposures is performed to detect asymptomatic infection in the HCT donor or candidate. Some tests are recommended for all HCT donors and candidates, whereas others are appropriate in selected individuals with epidemiologic risk factors (table 1) [1,2]. Serologic testing is used as an indicator of significant past exposures.

The evaluation for HCT candidates is discussed in greater detail separately. (See "Evaluation for infection before hematopoietic cell transplantation".)

Donor selection is discussed below. (See 'Donor selection' below.)

TIMELINE FOR INFECTIONS — The types of infections to which HCT recipients are most vulnerable can be roughly divided based upon the time elapsed since transplantation. The three periods are:

Pre-engraftment – From transplantation to approximately day 30

Early postengraftment – From engraftment to day 100

Late postengraftment – After day 100

In general, allogeneic HCT recipients are at risk for infection during all three periods (figure 1), whereas autologous HCT recipients are typically only vulnerable to infection during the pre- and immediate postengraftment periods (figure 2). During each of these time periods, patients can develop bacterial, fungal, viral, and/or parasitic infections, although certain pathogens tend to cause disease during some of these periods more than others (table 2).

This division into time periods is artificial, but it is helpful in the management of HCT recipients. The timing and length of interval of each of these phases may vary according to the source of stem cells, degree of human leukocyte antigen (HLA) and minor histocompatability antigen match, type and intensity of conditioning regimen used, and any manipulation the graft has had prior to transplant, immunosuppressive therapy (especially glucocorticoids), and the presence of graft-versus-host disease.

The timeline for infections is discussed in greater detail separately. (See "Overview of infections following hematopoietic cell transplantation", section on 'Timeline for infections'.)

HIGH-RISK PATIENTS — It is important to identify the population at high risk for infections and also the magnitude of and the period of maximum risk in order to identify those patients likely to benefit from prophylaxis (table 3).

There are three factors that interact to determine the risk of infection in HCT recipients (figure 3):

The patient's net state of immunosuppression

The patient's exposure to pathogens

The presence of organ damage

GENERAL STRATEGIES TO REDUCE RISK — This section discusses general strategies to reduce the risk of infection following HCT. An overview of the risk of infection following HCT is presented separately. (See "Overview of infections following hematopoietic cell transplantation", section on 'Risk of infection'.)

Donor selection — Donor selection is critical to reducing the risk of complications that increase the risk for infections following allogeneic HCT including graft-versus-host disease (GVHD), graft failure, and delayed immune reconstitution [3]. Transplantation of stem cells from donors who are not fully histocompatible by high-resolution matching for human leukocyte antigen (HLA) gene donor cells at the A, B, C, and DR loci is more frequently associated with graft failure and GVHD [4]. Donor selection is discussed in greater detail separately. (See "Donor selection for hematopoietic cell transplantation".)

Donor/recipient cytomegalovirus (CMV) serostatus – The risk of posttransplant CMV infection and CMV disease is significantly influenced by both donor and recipient CMV serostatus, and the serostatus should determine the appropriate prophylaxis or pre-emptive strategy. A recipient who is CMV seropositive and receives a graft from a donor who is CMV seronegative (CMV D-/R+) is at greatest risk for the development of CMV disease after transplant. These issues are discussed separately. (See "Prevention of viral infections in hematopoietic cell transplant recipients", section on 'Cytomegalovirus' and "Donor selection for hematopoietic cell transplantation", section on 'CMV status'.)

Donor/recipient hepatitis B virus serostatus – Active hepatitis can occur after transplant if either the donor or recipient is seropositive. Monitoring and prophylaxis strategies are discussed separately. (See "Prevention of viral infections in hematopoietic cell transplant recipients", section on 'Hepatitis B virus' and "Hepatitis B virus reactivation associated with immunosuppressive therapy".)

Pre-HCT testing — To protect the HCT recipient from acquiring various infections from the donor, both the donor and recipient must undergo a history and physical examination as well as screening tests prior to HCT (table 1). This is discussed in detail separately. (See "Evaluation for infection before hematopoietic cell transplantation".)

Conditioning regimen and dose of hematopoietic cells — Because persistence of host T cells or natural killer cells may cause graft rejection (and hence increase the risk for infection), an effective conditioning regimen should be used. The infusion of an adequate number of stem cells is critical for prompt hematopoietic recovery in both autologous and allogeneic HCT recipients, especially in patients receiving reduced intensity conditioning and patients receiving grafts from mismatched donors. (See "Preparative regimens for hematopoietic cell transplantation" and "Hematopoietic cell transplantation (HCT): Sources of hematopoietic stem/progenitor cells" and "Hematopoietic support after hematopoietic cell transplantation".)

Avoidance of excessive immunosuppression and myelosuppression — Glucocorticoids are generally avoided as prophylaxis for GVHD. When needed to treat GVHD, the lowest possible dose of glucocorticoids should be used followed by a rapid taper, and every effort should be made to ensure the proper diagnosis of GVHD prior to commencing glucocorticoids. (See "Treatment of acute graft-versus-host disease" and "Treatment of chronic graft-versus-host disease" and "Prevention of graft-versus-host disease", section on 'Introduction'.)

It is also important to avoid the prolonged use of potentially myelosuppressive drugs, when possible, and to adjust their doses carefully when used. Examples of such drugs are linezolid, ganciclovir, valganciclovir, trimethoprim-sulfamethoxazole, mycophenolate mofetil, methotrexate, and, occasionally, the H2 blockers and intravenous vancomycin.

ANTIMICROBIAL PROPHYLAXIS OR PRE-EMPTIVE THERAPY

Definitions — Approaches to the prevention of infection in HCT recipients include primary prophylaxis, secondary prophylaxis, and pre-emptive therapy.

Primary prophylaxis – Primary prophylaxis involves the administration of an antimicrobial drug to prevent infection in patients at increased risk.

Secondary prophylaxis – Secondary prophylaxis involves the administration of prophylactic doses of an antimicrobial drug to prevent recurrent infection.

Pre-emptive therapy – Pre-emptive therapy involves starting antimicrobial therapy based upon screening with a sensitive assay (eg, polymerase chain reaction [PCR]) in an attempt to detect early infection. The goal of pre-emptive therapy is to avoid progression to invasive disease. Pre-emptive therapy may be favored over prophylaxis when the antimicrobial therapy is particularly toxic (eg, for cytomegalovirus). (See "Prevention of viral infections in hematopoietic cell transplant recipients", section on 'Pre-emptive therapy'.)

Timing of antimicrobial prophylaxis — Antimicrobial prophylaxis should be initiated at the beginning of the risk period, typically with the conditioning regimen or at the time of stem cell infusion (to avoid deleterious interactions with the conditioning regimen) but, in case of myelosuppressive antimicrobials, such as trimethoprim-sulfamethoxazole, at the time of engraftment and should be continued throughout the period at risk for infection.

Antibacterial prophylaxis

Before engraftment — Antibacterial prophylaxis with a fluoroquinolone has been shown in randomized trials and meta-analyses to reduce all-cause mortality, infection-related mortality, fever, and infections in high-risk neutropenic patients, including allogeneic HCT recipients.

Myeloablative allogeneic HCT – Based upon the available data, we suggest fluoroquinolone prophylaxis for patients undergoing allogeneic HCT who have received myeloablative conditioning regimens. If a fluoroquinolone is contraindicated, a third-generation cephalosporin, such as cefpodoxime, can be used although there are few studies supporting its use [5]. Generally, trimethoprim-sulfamethoxazole is avoided during the pre-engraftment period due to the concern for myelosuppression.

Reduced-intensity and nonmyeloablative conditioning allogeneic HCT – This type of HCT is generally associated with a short period of neutropenia and, therefore, there is typically no need for antibiotic prophylaxis.

Autologous HCT – Antibacterial prophylaxis is sometimes given to autologous HCT recipients transplanted for hematologic malignancies who receive intensive conditioning regimens, but the degree of mucosal injury of many of the conditioning regimens is less severe and the shorter time to engraftment make the need for prophylaxis less clear than for allogeneic HCT recipients. Autologous HCT recipients who have received or will receive immunosuppressive therapies increasing the risk for bacterial infections may also be given antibacterial prophylaxis. The decision of whether to give antibacterial prophylaxis to autologous HCT recipients should be made on a case-by-case basis.

There are several potential downsides to using fluoroquinolone prophylaxis, including toxicities and the potential for promoting resistance.

The evidence to support antibacterial prophylaxis in HCT recipients is discussed in detail separately. (See "Prophylaxis of infection during chemotherapy-induced neutropenia in high-risk adults", section on 'Antibacterial prophylaxis'.)

After engraftment — Antibiotic prophylaxis should generally be stopped at neutrophil engraftment. However, allogeneic HCT recipients who develop chronic graft-versus-host disease (GVHD) are at substantial risk for serious infection with encapsulated bacteria, especially Streptococcus pneumoniae, and they should receive prolonged antibiotic prophylaxis [1]. The optimal duration of prophylaxis against S. pneumoniae and other encapsulated bacteria is not clear. We continue it for as long as the patient is receiving active immunosuppressive therapy (ie, treatment for GVHD), whereas some centers continue it for a longer period beyond cessation of active immunosuppressive therapy. Antibiotics with activity against encapsulated bacteria include penicillin, trimethoprim-sulfamethoxazole (TMP-SMX), and levofloxacin, but rates of resistance to these agents vary in different geographic regions. The choice of antibacterial drug should be based upon local resistance patterns. In areas with a low rate of resistance to penicillin, we favor penicillin.

Antifungal prophylaxis — Both yeasts and molds cause serious invasive fungal infections in HCT recipients. Prior to the routine use of antifungal prophylaxis, Candida spp accounted for the majority of fungal infections that occurred during the pre-engraftment period of HCT, followed by Aspergillus spp. HCT recipients are at highest risk for Candida infections during the pre-engraftment period (figure 1). Aspergillus is the most common mold pathogen in HCT recipients, occurring most commonly during the postengraftment period in allogeneic HCT recipients with severe GVHD.

Antifungal prophylaxis targeting either Candida spp alone or Candida spp plus molds is generally recommended in all HCT recipients. The evidence to support this practice and specific recommendations about antifungal prophylaxis are presented separately. (See "Prophylaxis of invasive fungal infections in adult hematopoietic cell transplant recipients".)

Pneumocystis prophylaxis — For allogeneic HCT recipients, we recommend that prophylaxis against Pneumocystis jirovecii (formerly P. carinii) pneumonia (PCP) be started after neutrophil engraftment and continued for as long as immunosuppressive therapy is given [1]. The typical duration of PCP prophylaxis is six months in allogeneic HCT recipients but is longer in those requiring treatment for GVHD. Early discontinuation of PCP prophylaxis in allogeneic HCT recipients has been associated with PCP [6].

Among autologous HCT recipients, PCP prophylaxis should be considered for those with underlying hematologic malignancies such as lymphoma, myeloma, or leukemia, those receiving myeloablative conditioning regimens, those with graft manipulations (eg, CD34 selection), those receiving high-dose glucocorticoids, and those who have recently received a purine analog (eg, fludarabine, cladribine). In autologous HCT recipients, when PCP prophylaxis is indicated, it is typically continued for three to six months following transplantation (or longer for those requiring immunosuppressive drugs).

TMP-SMX is the preferred regimen because it appears to be the most efficacious; breakthrough PCP infections occur more frequently with other agents [1,7]. TMP-SMX also has activity against Toxoplasma gondii, Nocardia spp, Listeria monocytogenes, and various respiratory and enteric pathogens. Because of the concern about myelosuppression and the low risk of PCP during the first month after HCT, TMP-SMX is generally started after engraftment. It is continued until immunosuppressive therapy is completed.

PCP prophylaxis is discussed in greater detail separately. (See "Treatment and prevention of Pneumocystis pneumonia in patients without HIV", section on 'Prophylaxis'.)

Toxoplasma gondii prophylaxis — Toxoplasmosis is an uncommon (<1 percent) but potentially fatal opportunistic parasitic infection that can occur in HCT recipients, particularly in endemic areas [8,9]. Most cases of toxoplasmosis occur due to reactivation in allogeneic HCT recipients, particularly in those with GVHD or in umbilical cord transplant recipients [10-16]. Rare cases of donor-derived infections have been reported [17].

Although toxoplasmosis has been reported following autologous HCT [18], the risk is very low unless CD34 selection is performed or additional T cell immunosuppressive therapies are given [19,20].

As noted above, allogeneic HCT recipients should receive TMP-SMX for PCP prophylaxis from engraftment until immunosuppressive therapy is discontinued; TMP-SMX is also effective prophylaxis for toxoplasmosis. For patients who cannot take TMP-SMX, alternative (but less well-studied) prophylaxis regimens include clindamycin, pyrimethamine plus leucovorin, pyrimethamine plus sulfadiazine, or pyrimethamine and sulfadoxine plus leucovorin [1,21].

For patients who cannot take TMP-SMX, an alternative to using a prophylactic regimen other than TMP-SMX is to screen high-risk (GVHD, umbilical cord blood graft) Toxoplasma-seropositive patients with quantitative PCR following transplantation [1,15,22], with initiation of pre-emptive therapy in patients who have a positive PCR assay.

Tuberculosis prophylaxis — Prophylaxis against tuberculosis (TB) in HCT recipients should be reserved for patients identified as high risk during the pretransplant evaluation. (See "Evaluation for infection before hematopoietic cell transplantation", section on 'Screening for tuberculosis'.)

Although there are no data regarding the efficacy of prophylaxis of TB in HCT recipients, prophylaxis is recommended for individuals at increased risk for TB reactivation given the risk of reactivation following HCT [1,23].

We suggest isoniazid (INH) prophylaxis in the HCT candidates or recipients who [1]:

Have been exposed to an individual with active sputum smear-positive pulmonary or laryngeal TB, regardless of the HCT candidate’s or recipient’s tuberculin skin test (TST) or interferon-gamma release assay (IGRA) status or

Have a positive TST result, regardless of prior Bacille-Calmette Guérin (BCG) status, without previous treatment for latent TB and with no evidence of active TB or

Have a positive IGRA result, without previous treatment for latent TB and with no evidence of active TB

INH prophylaxis should generally be initiated at the completion of the conditioning regimen; in some patients, it can be initiated prior to conditioning if the agents in the conditioning regimen do not have significant interactions with INH and if the patient is thought to be at particularly high risk of TB reactivation [1]. Drug interactions, especially with the mold-active azoles, can lead to significant toxicity, and concomitant administration should be avoided. The treatment of latent TB is discussed in greater detail separately. (See "Treatment of tuberculosis infection (latent tuberculosis) in nonpregnant adults without HIV infection".)

Details about specific interactions may be obtained by using the drug interactions program included within UpToDate.

Strongyloides prophylaxis — HCT candidates with pretransplant screening tests positive for Strongyloides stercoralis or those with unexplained eosinophilia and a travel or residence history suggesting exposure to S. stercoralis should receive empiric treatment prior to HCT with ivermectin (200 mcg/kg per day orally daily for two consecutive days, repeat after two weeks) [1].

Antiviral prophylaxis or pre-emptive therapy — Viruses of major importance in HCT recipients include members of the herpesvirus family (herpes simplex virus, varicella-zoster virus, cytomegalovirus, Epstein-Barr virus, and human herpes virus 6), respiratory viruses (eg, influenza, parainfluenza, respiratory syncytial virus, adenovirus, SARS-CoV-2), and BK virus. Antiviral prophylaxis or pre-emptive therapy against some of these viruses is recommended for HCT recipients; this is discussed in detail separately. (See "Prevention of viral infections in hematopoietic cell transplant recipients".)

ADDITIONAL MEASURES — Other important strategies should be employed to reduce the risk of infection in HCT recipients, including infection control measures, immunizations, and others.

Infection control measures — Effective infection control measures can reduce exposure of HCT recipients to potential nosocomial pathogens. Patients and health care workers should be educated about the risk of and methods to prevent acquisition of these organisms. The following recommendations have been adapted from the 2009 HCT guidelines; our recommendations are generally in keeping with those guidelines [1]:

Protective isolation and room ventilation – Protective isolation should be used during hospitalization for all allogenic HCT recipients, especially during the early phases after HCT, and can also be used for autologous HCT recipients, depending on the availability of rooms in which protective isolation measures can be implemented.

Generally, the following measures should be used for room ventilation when protective isolation is indicated: ≥12 air exchanges per hour, high efficiency particulate air (HEPA) filters, directed airflow (so that air intake occurs at one side of the room and air exhaust occurs at the opposite side), positive air pressure differential between the patient's room and the hallway, well-sealed rooms, continuous pressure monitoring, and self-closing doors to maintain constant pressure differentials. The use of laminar airflow remains controversial because the possible benefit remains unclear [24]; laminar airflow is not recommended for newly constructed patient rooms. However, for patients with infections that can be transmitted via airborne particles (eg, SARS-CoV-2, disseminated zoster, pulmonary tuberculosis), a negative air pressure differential should be used to help prevent transmission to other patients and hospital staff.

Construction or renovation – If construction or renovation occurs, intensified mold control measures should be put into place to minimize fungal spore counts in patient rooms.

Cleaning – HCT units should be cleaned at least daily with special attention to dust control. Selection of furnishings should focus on creating and maintaining a dust-free environment.

Isolation and barrier precautions – Published guidelines for hospital isolation should be followed to prevent health care–associated infections [25]. At a minimum, standard precautions should be used. Standard precautions include hand hygiene and appropriate personal protective equipment (gloves, surgical masks or eye and face protection, and gowns) during procedures that are likely to generate splashes or sprays of blood, body fluids, secretions or excretions, or cause soiling of clothing. We use gloves and masks during respiratory virus outbreaks and during respiratory virus season in an attempt to further reduce the risk of transmission of respiratory viruses from health care workers and visitors to HCT recipients. Some centers use gloves and masks year-round.

Most studies have failed to establish a clear benefit for masks in protecting either other patients or health care workers [26-28]. However, two studies did show a reduction in respiratory virus infections among HCT recipients when masks were worn by all individuals who had direct contact with the patients [29,30].

When an HCT recipient is suspected of having or proven to have an infection requiring additional precautions (eg, airborne, droplet, or contact precautions), they should be implemented as indicated. (See "Infection prevention: Precautions for preventing transmission of infection" and "Prevention of viral infections in hematopoietic cell transplant recipients", section on 'Infection control'.)

Although there is insufficient evidence establishing its efficacy, HCT recipients may benefit from wearing masks or N95 respirators when they are outside of their hospital rooms, especially when hospital construction or renovation is occurring.

After discharge, we advise HCT recipients to wear masks in doctors’ offices and waiting rooms (but not in homes or outdoors) during the first three months following HCT or longer if they are receiving treatment for graft-versus-host disease (GVHD). We also advise avoidance of large crowds and avoidance of dusty, windy outdoor venues. We suggest that HCT recipients shop and dine out at times when they can avoid close contact with individuals other than their caregivers. The efficacy of these measures has not been established.

Hand hygiene – Hand hygiene is the mainstay of infection prevention in the hospital and is an essential element of standard precautions for all patients, including HCT recipients. Hand hygiene involves the use of alcohol-based hand rubs and/or handwashing with soap and water. In the absence of visible soiling of hands or contact with spore-forming organisms (eg, Clostridioides difficile), the preferred method of hand hygiene is with an alcohol-based hand rub because of its superior microbicidal activity, reduced drying of the skin, and convenience. When hands are visibly dirty or when the patient has infection with a spore-forming organism, they should be washed thoroughly using soap and water. (See "Clostridioides difficile infection: Prevention and control", section on 'Hand hygiene' and "Infection prevention: Precautions for preventing transmission of infection", section on 'Hand hygiene'.)

Care of intravascular catheters – Health care workers should follow established protocols for preventing intravascular catheter-associated infections. (See "Routine care and maintenance of intravenous devices".)

Avoidance of plants and flowers – Plants and dried or fresh flowers should not be allowed in hospital rooms during conditioning or after HCT to reduce possible exposure to mold and bacteria.

Disinfection of toys and play areas – Toys and play areas should be cleaned and disinfected frequently according to published recommendations.

Food safety – Although not well studied, we suggest that HCT recipients receive a diet less likely to expose HCT recipients to microbes than a usual diet. Examples of foods to avoid include raw or undercooked meat, poultry, fish, game, tofu; unpasteurized or raw milk; milk products made from unpasteurized or raw milk; and raw fruits and vegetables.

Herbal/naturopathic supplements – We advise that HCT recipients avoid herbal/naturopathic supplements, in part because they are often contaminated with molds and other pathogens and they have been associated with invasive mold infections in HCT recipients [31,32].

Infection control measures for HCT recipients, including recommendations for safe living following hospital discharge after HCT, are discussed in greater detail in the 2009 HCT guidelines.

Chlorhexidine bathing — Bathing patients daily with chlorhexidine gluconate, an antiseptic agent with broad-spectrum activity against many organisms, has been shown to be an effective method of decreasing both hospital-acquired infections and colonization with drug-resistant organisms, primarily among patients in the intensive care unit (ICU). Benefit has also been shown in HCT recipients [33]. We suggest chlorhexidine bathing for all HCT recipients.

In a trial that included over 7000 patients in both ICU and HCT units, there was a 23 percent reduction in the overall rate of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) acquisition with daily bathing with 2% chlorhexidine-impregnated washcloths compared with non-impregnated washcloths (5.1 versus 6.6 cases per 1000 patient-days, respectively) as well as a 28 percent reduction in the rate of hospital-acquired bloodstream infections (4.8 versus 6.6 cases per 1000 patient-days, respectively) [33]. The effect was greater among patients with a longer length of hospital stay and was predominantly driven by reduction in VRE rather than MRSA acquisition. Of note, the reduction in bloodstream infections with chlorhexidine use was greatest for coagulase-negative staphylococci and fungal infections; there was not a significant reduction in the incidence of central venous catheter–associated bloodstream infections involving gram-negative organisms, VRE, or MRSA.

Chlorhexidine bathing in ICU patients is discussed in detail separately. (See "Nosocomial infections in the intensive care unit: Epidemiology and prevention", section on 'Patient bathing/decolonization'.)

Blood products — To prevent transfusion-transmitted cytomegalovirus (CMV) disease in CMV-seronegative recipients whose donor is also CMV seronegative, blood products that are either obtained from CMV-seronegative donors or leukocyte-depleted should be used [34].

Iron overload, which may be caused by large numbers of red blood cell (RBC) transfusions, adversely affects the survival of HCT recipients, increasing the likelihood of infections and acute GVHD [35,36]. Transfusion of RBCs should therefore be minimized when possible. Several retrospective studies suggest iron overload may be associated with increased risk for posttransplant fungal and bacterial infection.

Immunomodulation — Various colony-stimulating factors (CSFs) and cytokines have been evaluated to improve the host's immune defenses. These agents include granulocyte colony-stimulating factor (G-CSF), granulocyte/macrophage colony-stimulating factor (GM-CSF; sargramostim), macrophage colony-stimulating factor (M-CSF), and interferon-gamma-1b. Of these, we suggest only the use of CSFs and only in selected patients, as discussed below. (See "Strategies for immune reconstitution following allogeneic hematopoietic cell transplantation", section on 'Therapeutic strategies to improve immune reconstitution'.)

Colony stimulating factors — We typically give G-CSF at a dose of 5 mcg/kg per day only to autologous HCT recipients who receive a suboptimal stem cell dose (eg, <5 million CD34+ cells/kg) and to allogeneic or autologous HCT recipients who have delayed neutrophil engraftment or whose white blood cell counts drop because of drugs (eg, ganciclovir) or infection.

G-CSF and GM-CSF shorten time to engraftment, especially when the stem cell content of the graft is suboptimal after autologous HCT [37-39]. In a meta-analysis, CSFs were associated with a small reduction in the risk of documented infections but did not affect infection-related mortality or treatment-related mortality [40]. At least one trial in allogeneic HCT recipients suggested decreased survival in patients who received G-CSF [41]. Thus, the use of growth factors is controversial in the setting of allogeneic HCT. (See "Hematopoietic support after hematopoietic cell transplantation", section on 'Growth factor support'.)

Intravenous immune globulin — We do not recommend the routine use of intravenous immune globulin (IVIG) in HCT recipients [1], as a meta-analysis of randomized trials did not show a benefit in terms of survival, infection prevention, or other transplant complications [42].

We check immunoglobulin G (IgG) levels in allogeneic HCT recipients with bacteremia or recurrent sinopulmonary infections and administer IVIG to those with low serum IgG levels (eg, <300 to 500 mg/dL) [1]. The dose and frequency needed to maintain adequate levels (eg, >500 to 700 mg/dL). Thresholds for IVIG treatment also varies among institutions and experts. The half-life of IVIG in HCT recipients is shorter (approximately 1 to 10 days) than in other patients (approximately 18 to 23 days) [1,43-45].

The efficacy of IVIG is best illustrated by reports of patients with common variable immunodeficiency (CVID). As an example, in a retrospective study of patients with CVID receiving IVIG, there was a higher incidence of serious infections (particularly pneumonia) in patients with IgG trough levels <400 mg/dL than in those with higher levels [46]. IVIG is discussed in greater detail separately. (See "Overview of intravenous immune globulin (IVIG) therapy" and "Intravenous immune globulin: Adverse effects" and "Treatment and prognosis of common variable immunodeficiency", section on 'Immune globulin replacement therapy'.)

Immunization

Active immunization — 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 following the return of immune competence (table 4). Other strategies for preventing infections in HCT recipients include pretransplant vaccination of HCT candidates with the usual vaccines that are indicated based upon age, vaccination history, and exposure history; and vaccination of household contacts. These issues are discussed in detail separately. (See "Immunizations in hematopoietic cell transplant candidates and recipients".)

Passive immunization — Use of IVIG or virus-specific immunoglobulins (eg, varicella-zoster immune globulin; VariZIG) for passive immunization against individual viruses is discussed separately. (See "Prevention of viral infections in hematopoietic cell transplant recipients", section on 'VZV postexposure prophylaxis' and "Prevention of viral infections in hematopoietic cell transplant recipients", section on 'CMV prevention' and "Prevention of viral infections in hematopoietic cell transplant recipients", section on 'Respiratory syncytial virus' and "Prevention of viral infections in hematopoietic cell transplant recipients", section on 'Hepatitis B virus' and "Hepatitis A virus infection: Treatment and prevention", section on 'Protection following exposure' and "Measles, mumps, and rubella immunization in adults", section on 'Post-exposure prophylaxis'.)

COVID-19 prevention — Pre-exposure prophylaxis, postexposure prophylaxis, vaccination, and other measures to prevent COVID-19 are discussed in detail separately. (See "COVID-19: Vaccines" and "COVID-19: Epidemiology, virology, and prevention", section on 'Prevention' and "COVID-19: Considerations in patients with cancer".)

SUMMARY AND RECOMMENDATIONS

Donor selection − Donor selection is critical for reducing the risk of complications that increase the risk for infections following allogeneic hematopoietic cell transplantation (HCT) including graft-versus-host disease (GVHD), graft failure, and delayed immune reconstitution (table 2). (See 'Donor selection' above.)

Immunosuppressive regimen − The posttransplant immunosuppressive regimen after allogeneic HCT should be chosen to strike a balance between sufficient immunosuppression to prevent graft rejection and GVHD as well as to avoid excessive immunosuppression or myelosuppression. In particular, glucocorticoids should be used judiciously because of their profound effect on both innate and acquired immunity, and, when used, doses should be tapered as rapidly as possible to minimize a high risk for infection. (See 'Avoidance of excessive immunosuppression and myelosuppression' above.)

Antibacterial prophylaxis following HCT

Allogeneic HCT with myeloablative conditioning − We suggest fluoroquinolone prophylaxis for allogeneic HCT recipients who have received myeloablative conditioning regimens (Grade 2A). Levofloxacin (500 or 750 mg orally once daily) and ciprofloxacin (500 or 750 mg orally twice daily) have been studied most extensively, and levofloxacin is favored in patients with increased risk for oral mucositis-related Streptococcus viridans infection.

Allogenic HCT with reduced-intensity conditioning − Reduced-intensity and nonmyeloablative conditioning allogeneic HCT is generally associated with a short period of neutropenia and, therefore, there is typically no need for antibiotic prophylaxis.

Autologous HCT − Antibiotic prophylaxis with a fluoroquinolone should be considered for autologous HCT patients transplanted for hematologic malignancies using conditioning regimens that cause significant mucosal injury or in patients who have received or will receive immunosuppressive therapies increasing the risk for bacterial infections. The decision of whether to give antibacterial prophylaxis to autologous HCT recipients should be made on a case-by-case basis. (See 'Before engraftment' above and "Prophylaxis of infection during chemotherapy-induced neutropenia in high-risk adults", section on 'Antibacterial prophylaxis'.)

Chronic GVHD − For HCT recipients with chronic GVHD, we suggest antibacterial prophylaxis with an agent active against Streptococcus pneumoniae (Grade 2C). We continue it for as long as the patient is receiving active immunosuppressive therapy (ie, treatment for GVHD). The choice of antibacterial drug should be based upon local resistance patterns. In areas with a low rate of resistance to penicillin, we favor penicillin. (See 'After engraftment' above.)

Pneumocystis prophylaxis

Allogeneic HCT recipients − For allogeneic HCT recipients, we recommend that prophylaxis against Pneumocystis jirovecii (formerly P. carinii) pneumonia (PCP) with trimethoprim-sulfamethoxazole (TMP-SMX) be started after engraftment and continued for as long as immunosuppressive therapy is given (Grade 1A). (See 'Pneumocystis prophylaxis' above.)

Autologous HCT recipients − We also recommend PCP prophylaxis for selected autologous HCT recipients, including those with underlying hematologic malignancies such as lymphoma, myeloma, or leukemia, those receiving myeloablative conditioning regimens, those with graft manipulations (eg, CD34 selection), and those who have recently received a purine analog (eg, fludarabine or cladribine) (Grade 1A). (See 'Pneumocystis prophylaxis' above and "Treatment and prevention of Pneumocystis pneumonia in patients without HIV".)

An additional benefit of TMP-SMX prophylaxis is that it prevents toxoplasmosis. (See 'Toxoplasma gondii prophylaxis' above.)

Prevention of viral and fungal infections − Strategies to reduce infections from fungi and viruses are important and are discussed in more detail separately. (See "Prevention of viral infections in hematopoietic cell transplant recipients" and "Prophylaxis of invasive fungal infections in adult hematopoietic cell transplant recipients".)

Infection control − Infection control measures, especially hand hygiene and the use of high efficiency particulate air (HEPA)-filtered patient rooms, can reduce the risk for infection and should be implemented. (See 'Infection control measures' above.)

Chlorhexidine bathing − We suggest chlorhexidine bathing for all HCT recipients (Grade 2B). (See 'Chlorhexidine bathing' above.)

Cautions with blood product use − Cytomegalovirus (CMV)-safe blood products (leukocyte filtered or from CMV-seronegative donors) should be used in CMV-seronegative allogeneic HCT recipients whose allografts came from CMV-seronegative donors. (See 'Blood products' above.)

Role of IVIG − Routine use of intravenous immunoglobulin (IVIG) has not been found to be effective in preventing infections or other HCT complications or in prolonging survival. We check immunoglobulin G (IgG) levels in allogeneic HCT recipients with bacteremia or recurrent sinopulmonary infections; we suggest administering IVIG to patients with levels <400 mg/dL (Grade 2B). (See 'Intravenous immune globulin' above.)

Vaccination − Immunizations should be given to HCT recipients following the return of immune competence to boost pathogen-specific immunity (table 4). Other strategies for preventing infections in HCT recipients include pretransplant vaccination of HCT candidates with the usual vaccines that are indicated based upon age, vaccination history, and exposure history; and vaccination of household contacts. (See "Immunizations in hematopoietic cell transplant candidates and recipients".)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Elias Anaissie, MD, who contributed to earlier versions of this topic review.

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Topic 1397 Version 37.0

References

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