Granulocyte transfusions in severe aplastic anemia: an eleven-year experience

Abstract

Background: Infections, particularly those caused by invasive fungi, are a major cause of death in patients with severe aplastic anemia. The purpose of this study was to analyze our experience with granulocyte transfusions in such patients.

Design and methods: A retrospective analysis was performed on all patients with severe aplastic anemia who had received granulocyte transfusions between 1997 and 2007 in our institute. Survival to hospital discharge was the primary outcome. Secondary outcomes included microbiological, radiographic and clinical responses of the infection at 7 and 30 days after initiating granulocyte therapy, and post-transfusion absolute neutrophil count, stratified by HLA alloimmunization status.

Results: Thirty-two patients with severe aplastic anemia underwent granulocyte transfusions; the majority had received horse antithymocyte globulin and cyclosporine A. One quarter of patients had demonstrable HLA alloimmunization prior to the initiation of granulocyte therapy. Infections were evenly divided between invasive bacterial and fungal infections unresponsive to maximal antibiotic and/or antifungal therapy. The median number of granulocyte components transfused was nine (range, 2-43). The overall survival to hospital discharge was 58%. Survival was strongly correlated with hematopoietic recovery. Among the 18 patients who had invasive fungal infections, 44% survived to hospital discharge. Response at 7 and 30 days correlated with survival. The mean post-transfusion absolute neutrophil count did not differ significantly between response groups (i.e. patients grouped according to whether they had complete or partial resolution of infection, stable disease or progressive infection). There was also no difference in mean post-transfusion absolute neutrophil count between the patients divided according to HLA alloimmunization status.

Conclusions: Granulocyte transfusions may have an adjunctive role in severe infections in patients with severe aplastic anemia. HLA alloimmunization is not an absolute contraindication to granulocyte therapy.

Figure 1.

(A) Relationship between ANC increment and granulocyte dose transfused for the first five non-alloimmunized patients who received 69 granulocyte concentrates. R²=0.26, p<0.01. (B) ANC over time for one patient who developed de novo HLA antibodies during the course of granulocyte therapy. Arrows denote granulocyte transfusions.

Figure 2.

Effect of splenomegaly and positive HLA antibody screen on absolute WBC increments 0–4 h post-transfusion. Ends of boxes represent 25% and 75% of data. End bars represent 5% and 95% of data. Dashed line inside box is the mean. Solid line inside the box is the median. Open circles represent outliers. Numbers on the x-axis refer to granulocyte transfusion episodes.