Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) in Stem Cell Transplant Recipients: Response to Immune Enhancement in Early Versus Late Serious Post-Transplant Infections

Background: The impact of GM-CSF therapy in SCT recipients with serious infection is not clear. We evaluated feasibility of GM-CSF therapy in transplant patients.

Methods: Forty-seven patients with severe infections who had received 7 or more doses of GM-CSF between 2000 and 2006 were evaluated. Response was considered at the end of GM-CSF therapy in patients with complete or partial response (CR/PR). All values are given as median ± s.d. Serious infections were defined as systemic/invasive infections requiring hospitalization.

Results: Age was 39 ± 18 years; 83% received allogeneic SCT, and 70% had leukemia. GVHD was noted in 36%; 60% of SCT recipients had cancer recurrence and 11% had graft failure. The APACHE II score was 15 ± 4. GM-CSF was given for 13 ± 12 (range, 7–57) doses. In only 1 of 5 patients with GM-CSF related adverse events (AEs), growth factor was discontinued due to persistent bone pain. Patients who received GM-CSF during late (>180 days) infections had higher CR/PR versus cytokine therapy for patients with early post-transplant infections (63% vs 35%, respectively; P = 0.06). Factors associated with treatment failure included: prior high-dose steroids (43% vs 4% in CP/PR; P = 0.01) multiple concurrent infections (65% vs 33% in CR/PR; P = 0.03), critical care unit stay (44% vs 5% in CR/PR; P = 0.001), mechanical ventilation (35% vs 4% in CR/PR; P = 0.01), serum bilirubin > 2mg/dL (30% vs 0%) in CR/PR; P = 0.004) and neutropenia (50% vs 17% in CR/PR: P = 0.02). Neutropenia was 25 ± 19 days in responders vs 34 ± 42 days in patients who failed treatment (P = 0.08). By logistic regression analysis, presence of multiple concurrent infections was associated with higher probability of death within 12 weeks of infection diagnosis (odds ratio, 4.76; 95% confidence interval, 1.1–20.5; P = 0.03).

Conclusions: Treatment with GM-CSF was tolerated without serious AEs and may improve outcomes in patients with late post transplant infections.