PF807 TREATMENT OF SEVERE INFECTIONS IN NEUTROPENIC PATIENTS WITH GRANULOCYTE TRANSFUSIONS: A SINGLE CENTRE EXPERIENCE IN 57 PATIENTS TREATED WITH 603 TRANSFUSIONS
Authors: Zima N. , Cukjati M. , Zver S. 
Published: June 2019

Background:

Life threathening infections among neutropenic patients treated with intensive chemotherapy or haematopoetic stem cell transplantation (HSCT) are frequent cause of morbidity and mortality. In the past decade granulocyte transfusions (GT) from donors stimulated with G‐CSF were increasingly used as a therapeutic modality and as preventive measure of such infections.

Aims:

To evaluate the efficacy and safety of GT and to evaluate possible correlation between the increase of the neutrophil count in peripheral blood and the neutrophil concentration in a single transfusion.

Methods:

We retrospectively analysed data of severly neutropenic patients that presented with severe infections and were treated with GT between 2012 and 2019. Primary end point was patients survival from infections. Secondary endpoints included the increase in neutrophil count in peripheral blood after one GT and to establish a cut off value for the neutrophil count in single apheresis product that is still clinically effective.

Results:

We included 57 patients, Female/Male ratio was 39%/61%, mean age 52y, and together received 603 GT. The majority (n = 47,82%) had acute leukemia and all of them were treated with intensive chemotherapy or underwent HSCT. They were all severely neutropenic (mean value of neutrophils at GT onset was 0,22x109/L) and had life threatening infection (mean CRP = 202) that wasn’t managable despite wide spectrum of antimicrobal and antifungal drugs. Some of them (n = 16,28%) had pulmonary infiltrates that were highly suspicious for invasive fungal infection. Patients received median of 8 GT with mean volume of 361 ml. Average time of treatment was 16 days. Mean neutrophil count per apheresis was 4,84x1010(135,5x109/L). We analysed the increment of neutrophils after 24 h and the average increase was 0,79x109/L(peak 14,50x109/L). The only GT toxicity we observed was respiratory distress in one patient (n = 1, 1,8 %). Overall mortality related to infections was 36,7% (n = 18). Among later, 6 patients (10,5%), achieved transient infection improvement on their clinical course but at the end died due to progression of haematological malignancy.

Summary/Conclusion:

The use of GT in neutropenic patients is safe with good survival rate and may reduce mortality rate due to severe infections. The results are consistent with previous literature data. As depicted on the graph (Graph 1), we couldn’t confirm the correlation between the increase of peripheral blood neutrophil count and the neutrophil concentration in a single aphaeresis unit. Consequentially, we couldn’t establish clear numeric cut value for clinical effectiveness of GT. This is likely due to the fact that it is hard to evaluate the dynamic of increase in neutrophils. Namely increases were higher towards the end of GT treatment, being associated with reestablished bone marrow regeneration. In some cases no increase was observed due to engraftment failure in HSTC recipients or because of hematologic malignancy progression. We also have to take in to consideration the ability of the transfused neutrophils to migrate to the site of inflamation and consequently, despite high apheresis concentration of neutrophils, disproportional values in peripheral blood. Although GT may offer effective and possible life saving therapeutic modality, it is difficult to confirm it's effectiveness, because of nonuniform patients population and lack of control group.

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