Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor (rhu GM-CSF) as Adjuvant Therapy for Invasive Fungal Diseases.

Abstract

Background:

Sargramostim (yeast-derived, glycosylated recombinant human granulocyte-macrophage colony-stimulating factor [rhu GM-CSF]) augments innate and adaptive immune responses and accelerates hematopoietic recovery of chemotherapy-induced neutropenia. However, considerably less is known about its efficacy as adjunctive immunotherapy against invasive fungal diseases (IFDs).

Methods:

The clinical courses of 15 patients with pediatric malignancies and IFDs treated adjunctively with sargramostim at a single institution were analyzed in a retrospective cohort review. Further, a systematic review of published reports of rhu GM-CSF for IFDs was also conducted.

Results:

Among 65 cases, 15 were newly described pediatric patients and 50 were previously published cases of IFDs treated with rhu GM-CSF. Among the newly reported pediatric patients, IFDs were caused by Candida spp., Trichosporon sp., and molds (Aspergillus spp., Rhizopus sp., Lichtheimia sp., and Scedosporium sp). Twelve (80%) were neutropenic at baseline, and 12 (80%) were refractory to antifungal therapy. Among 12 evaluable patients, the overall response rate was 92% (8 [67%] complete responses, 3 [25%] partial responses, and 1 [8%] stable). Treatment is ongoing in the remaining 3 patients. Among 50 published cases (15 Candida spp., 13 Mucorales, 11 Aspergillus spp., 11 other organisms), 20 (40%) had baseline neutropenia and 36 (72%) were refractory to standard therapy before rhu GM-CSF administration. Consistent with responses in the newly reported patients, the overall response rate in the literature review was 82% (40 [80%] complete responses, 1 [2%] partial response, and 9 [18%] no response).

Conclusions:

Sargramostim may be a potential adjunctive immunomodulator for selected patients with hematological malignancies and refractory IFDs.

• Authors: Tempe K Chen, Jagmohan S Batra, David E Michalik, Jacqueline Casillas, Ramesh Patel, Maritza E Ruiz, Harneet Hara, Bhavita Patel, Meena Kadapakkam, James Ch'Ng, Catherine B Small, Panagiotis Zagaliotis, Carolyn E Ragsdale, Luis O Leal, Emmanuel Roilides, Thomas J Walsh
• Journal: Open forum infectious diseases (Open Forum Infect Dis) Vol. 9 Issue 11 Pg. ofac535 (Nov 2022) ISSN: 2328-8957 [Print] United States
• PMID: 36381625 (Publication Type: Journal Article)
• Copyright: © The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.