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Improved surveillance, prophylaxis suggested for CMV in pediatric bone marrow transplantation
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Improved surveillance and pre-emptive therapies may be required to better manage late-onset cytomegalovirus infections among pediatric bone marrow transplant patients.
“Among allogeneic and autologous blood and marrow transplant recipients, infectious mortality accounts for 20% and 8% of all cases, respectively,” Hisham Abdel-Azim, MD, of the Children’s Hospital Los Angeles and the University of Southern California, and colleagues wrote. “There have been recent calls to develop new strategies to overcome the limitations of current antimicrobial regimens, particularly as this relates to viral complications following bone marrow transplant.”
To assess clinical practice patterns regarding infectious diseases among accredited pediatric bone marrow transplant centers, and the extent to which infection prevention guidelines have been implemented, researchers conducted an anonymous email survey of 64 bone marrow transplant center program directors. Selected program directors were asked to identify their clinical practices by choosing among listed options.
The researchers categorized the responses as complete and partial, with complete responses defined as 80% or more of questions answered. A partial response was defined as more than 50% and less than 100% of questions answered. The overall response rate was 56% with 24 complete responses and 12 partial responses.
Reported clinical practices were similar in terms of intravenous globulin administration, treatment of viral complications and environmental precautions.
However, researchers observed variations in clinical practice regarding the surveillance of late-onset cytomegalovirus (CMV) surveillance, with less than 50% reporting screening transplant recipients for CMV more than 100 days after transplant in cases of low CD4 count, seropositive recipients with a seronegative donor, recipients of unrelated, haploidentical or T-cell depleted grafts and recipients of umbilical cord blood grafts.
“A recent survey of CMV management among pediatric bone marrow transplantation programs, support our own finding that further attention to late-onset CMV surveillance strategies may be indicated,” Abdel-Azim and colleagues wrote. “Confusion regarding best practice for appropriate CMV surveillance strategies and whether pre-emptive therapy is associated with late-onset CMV disease, suggest that prospective studies are needed to promote a more harmonized management approach.”
Seventy percent of respondents (CI, 49%-84%) reported the use of voriconazole for antifungal prevention for transplant patients with a suspected or confirmed history of aspergillosis. Despite this practice, 56% (CI, 33%-77%) did not report therapeutic drug monitoring for the prophylactic use of voriconazole.
“Prospective studies are needed to address variability in screening for late onset CMV and to harmonize best practice,” the researchers wrote. “Variability in therapeutic drug monitoring of antimicrobials should be addressed.”
Disclosure: The researchers report no relevant financial disclosures.
Perspective
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Michael A. Pulsipher, MD
Abdel-Azim and colleagues report results of a survey conducted of infectious disease practices amongst Foundation for the Accreditation for Cellular Therapy-accredited pediatric HSCT programs in the United States. With consensus guidelines on various infection prevention and treatment practices in place, one would expect fairly consistent practice across centers. Looking deeper, however, it is not surprising that these investigators report variation in practice in many key areas; most of the variation noted occurs where the “consensus” is unclear. For example, it is not surprising that investigators are split between starting therapy for adenovirus at any level or a level in the blood plus confirmation from a different source when the recommendation is that no specific level shows just when to begin therapy. The fact that IV cidofovir is toxic therapy should certainly give practitioners pause before embarking.Similarly, with cytomegalovirus (CMV), 44% responded that they will confirm a positive response before initiating therapy. Given side effects with current therapy and the rapidity of verification sample turnaround, this may be more prudent than starting whenever CMV is detected, as is implied by the recommendations. The more interesting dilemma with CMV is when to continue screening for late-onset CMV infection. The recommendation to follow all patients “considered to be at risk for late CMV disease” means many things to may centers. Almost everyone agrees that patients with chronic graft-versus-host disease (cGVHD) need screening, but what about those with minimal cGVHD not on steroid therapy? Only half agreed to monitor when patients are on long-term steroid usage, likely because the dose of steroids was not specified, and patients on physiological steroid doses can be on them for extended periods of time, and likely don’t need CMV screening. Much more careful study should be done to understand when patients are immunologically at risk — CD4 count alone is not sufficient.
Another interesting observation made by the survey concerns the use of palivizumab (Synagis; MedImmune, AstraZeneca) for respiratory syncytial virus prophylaxis. Nearly half of centers do this in spite of no recommendation in the guidelines and little support in the literature. This is a study begging to be performed. Finally, a similar lack of sync with practice and recommendations is the use of antibiotic prophylaxis early after HSCT. More than a third of centers do this in spite of a recommendation stating that no prophylactic regimens are “recommended” in children, though some “experts” use levofloxacin (Levaquin, Janssen). Is this a recommendation? You don’t need it, but “experts” use it? An ongoing Children’s Oncology Group randomized trial is studying this issue, and results of the trial will be much more convincing than the untested opinions of a few “experts.”
Many of the differences between practice and recommendations come from variations in experience and training of transplant physicians, as well as differences in types of patients transplanted at a given center. But a lot of differences stem from inadequate study of these issues in children. Pediatric transplants are uncommon procedures, thus studies require significant cost for multicenter groups to perform. This paper reminds us that not only would it be useful to consider breaking out of old habits in the face of new recommendations, it is also a call for more study in areas where a scientifically sound answer may improve safety and reduce risk for transplant-related mortality in children undergoing HSCT.
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