Styczynski, J., Gil, L.; & EBMT Paediatric Diseases Working Party. (2008). Prevention of infectious complications in pediatric HSCT. Bone Marrow Transplantation, 42, S77–S81.

To analyze the current guidelines and recommendations for the prevention of infectious complications in adults and children undergoing hematopoietic stem cell transplantation (HSCT).

This resource is a guideline.  A mini-review of evidence-based recommendations was conducted on the prevention of infections after HSCT in children.  These recommendations were rated based on the strength of the recommendation and supporting evidence quality.  The evidence-based system (A-E, I-III) was used to establish the strength of the recommendations and the quality of the supporting evidence.

Databases searched were not stated.  The authors stated that they reviewed current guidelines, but the guidelines were not specifically identified.

Search keywords were prophylaxis, infection, hematopoietic SCT, strategy, and vaccination.

Studies were included in the review if they reported adults and children undergoing HSCT.  The exclusion criteria were not reported.

The study has clinical applicability for pediatrics.

In the hospital environment, cleaning all surfaces to prevent dust accumulation, separating patient wards from outside air, and housing patients in rooms with high-efficiency particulate absorption filters were category AII recommendations.  Having patients wear masks when going to unprotected areas and providing rooms with positive pressure were category BIII recommendations.  Hand washing to minimize hospital-acquired candidal and bacterial infections was rated AIII.  Antibacterial prophylaxis for all patients from conditioning through engraftment was strongly recommended (AI), with ciprofloxacin, levofloxacin, and amoxicillin-clavulanate.  Fungi prophylaxis was recommended with fluconasole, voriconazole, posaconazole, or (BII) itraconazole for all patients. Cytomegalovirus prophylaxis with ganciclovir was recommended (AI) for high-risk patients.  Herpes simplex virus prophylaxis for IgG-positive patients was recommended (AI) with valacyclovir. Varicella-zoster virus prophylaxis was recommended for IgG-positive patients.  Vaccinations were not supported by any AI recommendations.  Annual inactivated influenza viral vaccine and conjugated Streptococcus pneumonia vaccine for all patients undergoing HSCT both received a category AII recommendation.  Viral polio inactivated, hepatitis B, bacterial conjugated Haemophilus influenzae B, toxoid tetanus, toxoid diphtheria, and polysaccharide S. pneumonia vaccines all received category recommendations.  (See Table 1 for the evidence-based rating.)

Table 1 (as shown in the article)

“Category definition to determine strength of recommendation:

• (A)  Should always be offered
• (B)  Should generally be offered
• (C)  Optional
• (D)  Should generally not be offered
• (E)  Should never be offered

Category definitions to determine quality of supporting evidence

• (I)  Evidence from at least one properly randomized and controlled trial
• (II)  Evidence from at least one well-designed clinical trial without randomization, from cohort or case-controlled analytic studies (preferably from more than one center), or from multiple time series or dramatic results from uncontrolled experiments
• (III)  Evidence from opinions of respected authorities based on clinical experience, descriptive studies or reports of expert committees.”

Table 2 provides antimicrobial prophylaxis type, indication, first and second recommendation using A-E, I–III ratings, and when to begin and end therapy.  Table 3 lists recommendations for vaccinations after HSCT by delineating viral and bacteria vaccines, type of vaccine, time to begin, number of doses, indications, and recommendations using A-E, I–III categories.

Conflict of Interest: Jan Styczynski and Lidia Gil have received speakers’ fees from Medagro and MSD.

Cotrimoxazole or quinolones antibacterial prophylaxis has demonstrated efficacy for patients with cancer who are neutropenic and after autologous HSCT (category AI), but well-designed clinical trials specifically for patients undergoing allogeneic HSCT are not available.  Studies with mostly adults receiving fluoroquinolones for HSCT were analyzed to deem the safety for children.  Using fluoroquinolones safely in children is based on one double-blind, placebo-controlled, randomized pediatric clinical trial using amoxicillin clavulanate, and patients undergoing HSCT were not included. High- and intermediate-risk patients should be offered antifungal prophylaxis.  Fluconazole, micafungin (both category AI), and itraconazole (category BI) are recommended during pre-engraftment for antifungal prophylaxis.  In adults with severe acute or extensive chronic graft-versus-host disease, oral posaconazole has been shown to be effective in reducing invasive mycoses.  No data on dose and schedule were reported for pediatric dosing.  Oral valganciclovir has been shown to be effective when compared to intravenous ganciclovir, but no pediatric data were available, and the drug was not available in liquid suspension, which is often desirable for children.  Vaccination against influenza and S. pneumoniae for HSCT was strongly recommended (category AII for both).  Live tuberculosis should never be offered (EII).  Other vaccinations have the potential for decreasing post-HSCT risks for vaccine-preventable infections.  High quality supporting evidence used in this guideline was based on as little as one randomized, controlled trial, with no discussion of sample size, risk of bias, etc., making this a relatively low threshold for highly rated evidence.