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Difficulties with Fungal Infections in Acute Myelogenous Leukemia Patients: Immune Enhancement Strategies

The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA

Key Words. Invasive fungal infection • Immune enhancement • Granulocyte-macrophage colony-stimulating factor • Interferon-gamma

Correspondence: Correspondence: Amar Safdar, M.D., F.A.C.P., Department of Infectious Diseases, Infection Control, and Employee Health, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 402, Houston, Texas 77030, USA. Telephone: 713-792-0825; Fax: 713-794-4351; e-mail: asafdar{at}mdanderson.org

Disclosure: A.S. has acted as a consultant to Berlex and has a financial interest in Merck.

Invasive fungal infection in severely immunosuppressed patients with acute myelogenous leukemia (AML) remains a serious challenge because (a) of the higher rates of non–drug susceptible fungal sinopulmonary disease; (b) despite advances in diagnostic fungal assays, the correct identification of causative organism(s) is difficult, and antifungal drug susceptibility data are seldom available during clinical decision making; and (c) the increasing frequencies of zygomycosis, scedosporiosis, and highly virulent Candida tropicalis infection have undermined the gains attributed to effective anti-Aspergillus drug therapy. Recombinant cytokines, such as recombinant human (rh)GM-CSF and interferon (IFN)-, have been explored to augment host antifungal immune responses. These cytokines promote activation and recruitment of granulocyte and mononuclear phagocytic effector cells. Prophylaxis with rhGM-CSF was associated with significantly fewer life-threatening and serious (grade 3) infections, especially in older patients undergoing treatment for AML. The limited experience with rhGM-CSF for the treatment of invasive fungal infections in combination with antifungal drug(s) was associated with a favorable outcome, and in contrast to Escherichia coli–derived rhGM-CSF, the new preparation (sargramostim) was well tolerated and rarely associated with serious systemic toxicities. Similarly, IFN- has been successfully used in patients with antimicrobial drug–refractory and/or disseminated fungal infection. Most patients tolerate the T-helper type 1 protagonist cytokine without serious adverse events. In difficult-to-treat fungal infections, the addition of cytokines appears to improve outcome and may be considered early in severely immunosuppressed patients with AML.