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Prevention and therapy of fungal infections in bone marrow transplantation

Leukemia volume 17, pages 1038–1041 (2003)Cite this article

Prevention and treatment of invasive fungal infections (IFI) in bone marrow transplantation (BMT) are essential to successful outcome. Unfortunately, preventative therapies for fungal infections are often toxic and fungal infections are usually detected at an advanced stage, thus increasing the challenge for successful treatment. Critical issues in managing these infections are identifying them as early as possible and treating them aggressively with a multimodality approach (eg augmentation of host immunity, utilization of growth factors, control of permissive viral copathogens, and antimicrobial therapy). There are several important advances in this field, which will be discussed: (1) approach to prophylaxis in BMT patients, (2) antifungal susceptibility testing, (3) novel diagnostic strategies, and (4) new therapeutic approaches.

Understanding who is at risk and when the risk occurs is critical. With this in mind, there are three principles that are important to consider in the approach to fungal disease in this patient population. The first is pathogen exposure: colonization precedes disease. Colonization with Candida sp. is common and typically does not elicit any overt clinical response nor does it demand a therapeutic intervention, as Candida sp. may be part of the normal gastrointestinal and/or vaginal flora. Aspergillus colonization is extremely worrisome in the neutropenic patient and almost always requires an intervention. The second principle is host susceptibility, or the net state of immunosuppression. In the allogeneic vs autologous BMT patient, the duration of neutropenia, the development and treatment of graft-versus-host disease (GvHD), the administration of growth factors, and the presence of immunomodulating viruses (cytomegalovirus CMV, HHV-6) all have serious repercussions on the immune system. It is difficult to calculate immune impairment, so the timing and deployment of antimicrobials will be different for each patient. Previously, prolonged neutropenia imparted the greatest risk for IFI. Now the greatest risk in BMT patients may not be during neutropenia, but months later associated with the occurrence of GvHD. These patients need a modified pre-emptive approach to infection.1 Another issue to consider are the effects of novel immunotherapies (eg new conditioning regimens, monoclonal antibody therapy) (Marty FM et al. 42nd ICAAC, 2002; Abstract M-1234). As the implications of these new therapies emerge, we will have to modulate our preventative approach accordingly. A major challenge in developing diagnostics for detecting and therapeutics for treating IFIs is the limitations of the current gold standard case definition: a consensus panel defining proven, probable, and possible IFI based on clinical, radiographic, microbiologic, and histopathologic criteria.2 Recognizing the reservoir of patients colonized with epidemiologically important pathogens and proper identification of the period(s) of increased host susceptibility, will facilitate the development of rational preventative strategies for IFI.

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Authors and Affiliations

  1. Brigham and Women's Hospital, Dana-Farber Cancer Institute, Boston, MA, USA

    L R Baden

  2. Harvard Medical School, Boston, MA, USA

    L R Baden

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Baden, L. Prevention and therapy of fungal infections in bone marrow transplantation. Leukemia 17, 1038–1041 (2003). https://doi.org/10.1038/sj.leu.2402949

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