Immunomodulation Therapy for Invasive Aspergillosis: Discussion on Myeloid Growth Factors, Recombinant Cytokines, and Antifungal Drug Immune Modulation

Safdar, Amar

doi:10.1007/s12281-010-0006-x

Cited by 9 publications

(3 citation statements)

References 59 publications

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“…To improve treatment, researchers have explored the use of recombinant cytokines such as recombinant human granulocyte macrophage colony-stimulating factor (GM-CSF) and interferon-gamma (IFN-γ) to improve the hosts’ immune control of these life-threatening opportunistic infections [3]. In immunosuppressed animals, GM-CSF alone or in combination with IFN-γ has been shown to enhance the fungicidal activity of innate phagocytic cells [4, 5].…”

Section: Introductionmentioning

confidence: 99%

Granulocyte Macrophage Colony-Stimulating Factor in 66 Patients with Myeloid or Lymphoid Neoplasms and Recipients of Hematopoietic Stem Cell Transplantation with Invasive Fungal Disease

et al. 2012

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Background/Aims: Adding granulocyte macrophage colony-stimulating factor (GM-CSF) may improve the response to antifungal therapy in immunosuppressed patients with invasive fungal disease (IFD). Methods: We retrospectively assessed 66 patients in whom GM-CSF was given during antifungal therapy. Results: Severe neutropenia (77%) and refractory/relapsed cancer (65%) were common in the group. Prior to GM-CSF therapy, 15% of patients received high-dose corticosteroids for a median of 30 ± 16 days [median cumulative dose (c.d.) 1,184 ± 1,019 mg], and 9 received steroids during GM-CSF therapy for a median of 16 ± 12 days (median c.d. 230 ± 1,314 mg). Mild toxic effects were noted in 9% of patients; there were no cases of cardiopulmonary toxicity. All-cause deaths were observed in 68% of patients and 48% died of progressive IFD. High-dose corticosteroids prior to GM-CSF (OR 24; 95% CI 2.21–264.9; p ≤ 0.009), GM-CSF started in the intensive care unit (OR 10; 95% CI 1.66–63.8; p ≤ 0.01), concurrent granulocyte transfusions (OR 5; 95% CI 1.27–16.8; p ≤ 0.02) and proven/probable IFD (OR 4; 95% CI 1–16.2; p ≤ 0.05) predicted antifungal treatment failure. Conclusions: GM-CSF adjuvant therapy was tolerated without serous toxicity and antifungal treatment failure remained a challenge in patients treated with high-dose systemic corticosteroids.

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Section: Introductionmentioning

confidence: 99%

Granulocyte Macrophage Colony-Stimulating Factor in 66 Patients with Myeloid or Lymphoid Neoplasms and Recipients of Hematopoietic Stem Cell Transplantation with Invasive Fungal Disease

et al. 2012

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“…Various strategies for promoting immune defenses are currently under investigation . Examples include recombinant myeloid growth factors, Th1 cytokines, and adaptive immunotherapy . High‐dose granulocyte transfusions to mitigate severe neutropenia in patients with opportunistic fungal infections have yielded uncertain benefits …”

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confidence: 99%

Aerosolized Amphotericin B Lipid Complex as Adjunctive Treatment for Fungal Lung Infection in Patients with Cancer‐Related Immunosuppression and Recipients of Hematopoietic Stem Cell Transplantation

Safdar

Rodriguez

2013

Pharmacotherapy

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Aerosolized amphotericin B lipid complex (aeABLC) has been successfully used to prevent fungal disease. Experience with aeABLC as treatment of fungal lung disease is limited. We evaluated the safety and efficacy of aeABLC adjunct therapy for fungal lung disease in a retrospective study of 32 immunosuppressed adults. Acute leukemia (69%) and severe neutropenia (63%) were common. The median duration of aeABLC was 185 ± 424 days in patients who underwent allogeneic stem cell transplantation (56%). High-dose corticosteroids were administered during aeABLC in 28% of patients. Fungal lung disease was proven or probable in 41% of patients. Most patients (78%) received systemic antifungal therapy for a median of 14 ± 18 days before aeABLC. The median cumulative aeABLC dose was 1,050 ± 2,368 mg, and the median duration of aeABLC therapy was 28 ± 130 days. Most patients (78%) received 50 mg aeABLC twice daily. Partial or complete resolution of fungal lung disease was noted in 50% of patients. In 3 patients (9%) modest cough, mild bronchospasm, and transient chest pain with accompanying nausea and vomiting resolved completely after discontinuation of aeABLC. No patient required hospitalization for drug toxicity or had a serious (grade III or IV) drug toxicity. Treatment with aeABLC was tolerated without serious toxicity and may be considered in the setting of severe immunosuppression, cancer, and/or stem cell transplantation in patients with difficult-to-treat fungal lung disease.

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“…infection allows studying mechanisms of immune defense in these particular organs which, along with reduction in fungal burden, can provide an insight into efficacy of therapeutic tested. In view of need for immune intervention as an adjunct therapy of fungal diseases including aspergillosis and the gain in importance of immune modulating activity of some antifungal agents , the knowledge of tissue responses in systemic aspergillosis seems significant.…”

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confidence: 99%

Differential strain‐related tissue immune response to sublethal systemic Aspergillus fumigatus infection in mice

Mirkov

Glamočlija

Stošić‐Grujičić

et al. 2012

APMIS

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Using a nonlethal systemic Aspergillus fumigatus infection, we have recently shown that similarly efficient elimination of fungus from spleens of prototypic Th1 (C57BL/6) and prototypic Th2 (BALB/c) mice is associated with differential immune responses. In light of these data and given the disseminated character of infection, the aim of the present study is to explore whether there are also strain-dependent differences in antifungal responses in peripheral tissues of infected mice. Although similar efficiency of conidia removal was noted in liver and kidneys of both strains, BALB/c mice seemed more prone to tissue injury. Compared with other nonlymphoid organs, lungs proved immunologically the most responsive in systemic aspergillosis. Lower numbers of neutrophils and macrophages in the lungs of infected BALB/c mice, delayed and lower (compared with C57BL/6 mice) expression of their oxidative activity, along with late IFN-γ and upregulated IL-4 production by lung cells might be responsible for slower elimination of A. fumigatus from the lungs of this mouse strain. The data obtained imply that lungs should be viewed as mandatory organ in evaluation of immune-mediated antifungal potential of drugs in models of systemic/disseminated infection and that strain differences noted in tissue responses should be taken into account in these settings.

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Immunomodulation Therapy for Invasive Aspergillosis: Discussion on Myeloid Growth Factors, Recombinant Cytokines, and Antifungal Drug Immune Modulation

Cited by 9 publications

References 59 publications

Granulocyte Macrophage Colony-Stimulating Factor in 66 Patients with Myeloid or Lymphoid Neoplasms and Recipients of Hematopoietic Stem Cell Transplantation with Invasive Fungal Disease

Granulocyte Macrophage Colony-Stimulating Factor in 66 Patients with Myeloid or Lymphoid Neoplasms and Recipients of Hematopoietic Stem Cell Transplantation with Invasive Fungal Disease

Aerosolized Amphotericin B Lipid Complex as Adjunctive Treatment for Fungal Lung Infection in Patients with Cancer‐Related Immunosuppression and Recipients of Hematopoietic Stem Cell Transplantation

Differential strain‐related tissue immune response to sublethal systemic Aspergillus fumigatus infection in mice

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