Background 
Patients with severe aplastic anemia (SAA) develop high-risk infections. Prior data suggest efficacy and safety of granulocyte transfusion (GT) as an infection management tool in this population. A multicenter randomized control trial of GT in patients with severe neutropenia of varying etiologies did not reveal a significant difference in overall survival (OS) or microbial response but was limited by low enrollment and variable granulocyte dose. In this study of SAA patients who received GTs at our institution, we characterize patients’ clinical and survival outcomes and the role of GTs as a bridge to curative therapy. 

Methods 
SAA patients treated with immunosuppressive therapy who received GTs between 2011 and 2020 are included in our analysis. The primary outcomes are survival from first GT, including OS, and number of patients surviving to discharge and HSCT in patients awaiting HSCT. Secondary outcomes include evaluation of response at 30 days after initiation of GTs based on clinical, microbiological, and radiographical criteria. Cox proportional-hazards model was utilized to determine impact of neutrophil response and infection type on survival. Kaplan-Meier was used to assess OS. 

Results 
Twenty-eight SAA patients of median age 20 years (range 6-65 years) underwent 30 GT courses of median 8 products per course (range 1-39 products), over median 23.5 days (range 3-103 days), with a per-dose median 1.28 x 10^9 granulocyte cells/kg (range 0.45-4.52 x 10^9). Infection type included bacterial (n=15), fungal (n=12), and mixed (n=3). OS from initial GT was 50% with a median length of follow up at 550.5 days (range 2-4213 days). 18 of 28 (64.3%) patients survived to hospital discharge. Of the 21 patients awaiting HSCT during granulocyte therapy, 18 (85.7%) received HSCT. Patients achieving complete, partial or stable response at 30 days had significantly improved OS compared to non-responders (p=0.00004). Sex, type of infection, or % of days with ANC >200 cells/mcL during the granulocyte course, were not predictive of survival (p=0.52, p=0.7, p=0.28 respectively). 

Conclusion 
GTs of adequate dose and course duration are a valuable adjunctive therapy to manage severe infections in SAA patients and may be particularly valuable as a bridge to undergoing curative treatment with HSCT.

The Clinical Role of Granulocyte Transfusions in Severe Aplastic Anemia

Clinical and Translational Research 2

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