Granulocyte transfusions as adjunctive treatment of invasive fungal diseases in neutropenic patients

Objectives: The degree and duration of neutropenia are crucial prognostic factors in hematological patients (pts) with invasive infections. Since the introduction of granulocyte colony stimulating factor (G-CSF), there has been a renewal of interest in granulocyte transfusions (GTX). Aim of the study was to evaluate feasibility, efficacy and safety of GTX as adjunctive treatment of infections in neutropenic pts unresponsive to antimicrobial therapy. Methods: Retrospective analysis on adult patients with hematolog- ical malignancies (HM) and fever during neutropenia (ANC<500 · 106/l and anticipated duration >7 days) who received GTX after no clinical response to antimicrobial therapy. Volunteer donors received G-CSF 12 h before the first of two consecutive collection procedures (5 l gkg –1 ). All of them had signed an informed consent for G-CSF administration and leukapheresis. Results: During a 7 years period (2004–10) 46 courses of GTX were administered. Patients were suffering from acute leukemia (30 myeloid and five lymphoid), lymphoma (9), multiple myeloma (2). Overall, 209 GTX were administered, with a median of four GTX per episode of infection (range 1–20). Infections causing fever were identified in 41 episodes: the majority of them (24/41, 59%) were IFDs (including 1 case of mixed bacterial/fungal sepsis), while 17 cases were bacterial sepsis (17 cases). Remaining five episodes were classified as fever of unknown origin (FUO) (five cases). IFDs included 16 cases of pulmonary aspergillosis (proven/probable), five candidemia, one inva- sive zygomycosis, one invasive fusariosis and one infection due to Blastoschizomices capitatus. Donors’ mean white blood cell (WBC) count at first leukapheresis was 27 · 109/l (range 13–45); at second procedure WBC count was lower (15 · 109/l, range 8–33), as expected. The mean yield was 25.6 · 109 PMN (range 3.5–75.8) at first procedure and 11.1 · 109 PMN at the second one (range 0.6–42.4). Mean transfused dose was 3.7 · 109/kg at first day (range 0.6–9.6) and 1.4 · 109/kg at second day (range 0.1–4.7). The combination of antimicrobial therapy with GTX led to a favourable clinical response in 33 of 46 valuable pts (72%); the acute infection-attributable mortality rate at 30th day after the last GTX was 22% for IFDs, 29% for bacterial sepsis, and 40% for FUO. Conclusions: At preliminary analysis GTX may be safe and effica- cious in HM with severe infection to bridge the period of deep neutropenia, when antimicrobial therapy has failed. Controlled studies are needed to confirm this datum, and to define the proper role of this procedure and the optimal schedule for HM