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

Objectives:\r\nThe degree and duration of neutropenia are crucial\r\nprognostic factors in hematological patients (pts) with invasive\r\ninfections. Since the introduction of granulocyte colony stimulating\r\nfactor (G-CSF), there has been a renewal of interest in granulocyte\r\ntransfusions (GTX). Aim of the study was to evaluate feasibility,\r\nefficacy and safety of GTX as adjunctive treatment of infections in\r\nneutropenic pts unresponsive to antimicrobial therapy.\r\nMethods:\r\nRetrospective analysis on adult patients with hematolog-\r\nical malignancies (HM) and fever during neutropenia (ANC<500\r\n·\r\n106/l and anticipated duration >7 days) who received GTX after no\r\nclinical response to antimicrobial therapy. Volunteer donors received\r\nG-CSF 12 h before the first of two consecutive collection procedures\r\n(5\r\nl\r\ngkg\r\n–1\r\n). All of them had signed an informed consent for G-CSF\r\nadministration and leukapheresis.\r\nResults:\r\nDuring a 7 years period (2004–10) 46 courses of GTX were\r\nadministered. Patients were suffering from acute leukemia (30 myeloid\r\nand five lymphoid), lymphoma (9), multiple myeloma (2). Overall, 209\r\nGTX were administered, with a median of four GTX per episode of\r\ninfection (range 1–20). Infections causing fever were identified in 41\r\nepisodes: the majority of them (24/41, 59%) were IFDs (including 1\r\ncase of mixed bacterial/fungal sepsis), while 17 cases were bacterial\r\nsepsis (17 cases). Remaining five episodes were classified as fever of\r\nunknown origin (FUO) (five cases). IFDs included 16 cases of\r\npulmonary aspergillosis (proven/probable), five candidemia, one inva-\r\nsive zygomycosis, one invasive fusariosis and one infection due to\r\nBlastoschizomices capitatus.\r\nDonors’ mean white blood cell (WBC) count at first leukapheresis\r\nwas 27\r\n·\r\n109/l (range 13–45); at second procedure WBC count was\r\nlower (15\r\n·\r\n109/l, range 8–33), as expected. The mean yield was\r\n25.6\r\n·\r\n109 PMN (range 3.5–75.8) at first procedure and 11.1\r\n·\r\n109\r\nPMN at the second one (range 0.6–42.4). Mean transfused dose was\r\n3.7\r\n·\r\n109/kg at first day (range 0.6–9.6) and 1.4\r\n·\r\n109/kg at second\r\nday (range 0.1–4.7).\r\nThe combination of antimicrobial therapy with GTX led to a\r\nfavourable clinical response in 33 of 46 valuable pts (72%); the acute\r\ninfection-attributable mortality rate at 30th day after the last GTX was\r\n22% for IFDs, 29% for bacterial sepsis, and 40% for FUO.\r\nConclusions:\r\nAt preliminary analysis GTX may be safe and effica-\r\ncious in HM with severe infection to bridge the period of deep\r\nneutropenia, when antimicrobial therapy has failed. Controlled studies\r\nare needed to confirm this datum, and to define the proper role of this\r\nprocedure and the optimal schedule for HM