GRANULOCYTE TRANSFUSIONS IN THE TREATMENT OF SEVERE INFECTIONS DURING PROLONGED NEUTROPENIA: SINGLE CENTER EXPERIENCE IN YEARS 2005 - 2014

Background
Use of granulocyte transfusions (GT) in patients with hematologic malignancy and prolonged neutropenia complicated with severe infection represents a strategy which positive and negative aspects are discussed.

Aims
To evaluate the efficacy and safety of GT applied over the last ten years period (2005-2014).  

Methods
A single center retrospective analysis was performed. GT were collected after stimulation with 40mg i.v. Solu-Medrol from unrelated AB0 and Rh compatible donors. HLA compatibility was not evaluated and family donors were not used. Separation was performed at Cobe Spectra - Caridian BCT blood separator. GT were stored at room temperature and given to the patients on the day of collection after irradiation of the packs with 32 Gy using Gammacell 3000 Elan blood irradiator (Cs¹³⁷). Decisions to give GT in individual patients were made collectively after agreement minimally of 3 physicians (usually patients´ physician, head of the ward and head of Department). Decisions to stop GT treatment were taken according to clinical response to GT and degree of hematologic reconstitution. All patients were pre-medicated with Hydrocortison 100mg i.v. given immediately prior transfusion.

Results
GT were given to 41 patients (15 female and 26 male) at age from 22 to 69 years (median 45.5). There were 26 cases of acute leukemia, 7 patients with myelodysplastic syndrome, 5 patients with chronic lymphocytic leukemia and 3 patients with lymphoma. In most patients disease was active at the time of GT initiation (30; 73.2%), only 11 patients were in hematologic remission. 30 patients were after chemotherapy while 3 patients were after allogeneic hematopoietic stem cell transplantation. Duration of severe neutropenia (less than 0.5x10⁹/l) was from 4 to 80 days (median 19 days). Antibiotics were applied in all patients for 1 to 126 days (median 14 days) before initiation of GT. The main clinical indications were soft-tissue inflammations (26 cases) and pneumonias (16). 14 patients have suffered from proven invasive fungal infections (9 aspergilosis and 5 candidiasis) while coincident Gram-positive or Gram-negative sepsis was present in 9 and 16 cases, respectively, complicated in 12 patients with septic shock. Together 191 GT were given – in a single patient from 1 to 17 GT (median 3.5). GT contained from 0.5 to 3.0x10¹⁰ granulocytes per one transfusion unit (median 1.3x10¹⁰). No side-effects both in donors and patients were recorded. Decrease of fever, complete resolution of infection and clinical improvement after GT was observed in 36 (87.8%), 29 (72.5%) and 34 (82.9%) of patients, respectively. Clinical deterioration occurred in 6 (14.6%) patients (4 – 9.8% – of these were fatalities). In six patients immediately after GT treatment allogeneic stem cell transplantation was performed. We have not observed any significant clinical consequences of GT in these patients after transplantation, one patient transplanted with active disease died early after relapse of acute leukemia while all other patients achieved full donor chimerism with remission of hematologic disorder.

Summary
We can conclude, that in our hands GT harvested from unrelated donors after stimulation with steroids and transfused in selected patients with severe infections during prolonged neutropenia have a high efficacy and safety and enabled not only successful management of infections in most cases but also safe proceeding to allogeneic stem cell transplantation leading to cure in a significant proportion of our patients. Acknowledgement: Grant of IGA LF UP 01-2015.

Keyword(s): Granulocyte transfusion

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