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

Abstract

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.

Acute Invasive Fungal Rhinosinusitis in Children With Hematologic Malignancies: Outcome of Surgical Treatment

“…Conservative treatment of AIFR includes reversing the underlying immunosuppression (i.e., cessation of steroid and chemotherapy, and administration of granulocyte colony-stimulating factor) in addition to providing systemic antifungal medication [6]. The use of hyperbaric oxygenation as an adjunctive modality has been reported, with uncertain therapeutic effects [7].…”

Treatment Options in Invasive Aspergillosis

“…Nevertheless, in a retrospective human study of 66 neutropenic patients who received GM-CSF, Safdar et al noted a 24 higher odds of antifungal treatment failure in the 15% receiving high-dose corticosteroids, but IFI-related deaths was significantly lower among GM-CSF responders (9%) compared with non-responders (94%) ( p =0.0001), based on clinical and/or radiographic progression. No serious toxicities were reported, though increased capillary permeability issues had been suggested previously [69]. …”

Promising immunotherapy against fungal diseases

“…66 patients with hematological malignancies or HSCT received rhGM-CSF as immune therapeutic adjuvant to treat IFIs [54]. GM-CSF administration turned out to be safe and well tolerated, but contrary to the experiments in mice, the addition of GM-CSF during high-dose corticosteroid therapy resulted in treatment failure.…”

“…GM-CSF administration turned out to be safe and well tolerated, but contrary to the experiments in mice, the addition of GM-CSF during high-dose corticosteroid therapy resulted in treatment failure. A significantly better outcome occurred in more than 50% of the patients upon administration of GM-CSF during antineoplastic therapy [54]. It needs further studies to evaluate GM-CSF efficiency and exact mode of action in IFI treatment of immunosuppressed individuals.…”

“…Further, a retrospective study investigated the usage of granulocyte-macrophage colony-stimulating factor (GM-CSF) [54] as GM-CSF alone or in combination with IFN-γ improved the fungicidal activity of innate phagocytic cells in animal studies [55]. 66 patients with hematological malignancies or HSCT received rhGM-CSF as immune therapeutic adjuvant to treat IFIs [54].…”