Therapeutic Granulocyte Transfusions in Neutropenic Patients with Invasive Pulmonary Aspergillosis,

Granulocyte transfusions (GTX) are used as an additional therapeutic option in patients with severe neutropenia following chemotherapy constituting an increased risk for life-threatening bacterial and fungal infections. We hypothesized that interventional GTX would provide a clinical benefit for neutropenic patients with invasive pulmonary aspergillosis (IPA). Methods: We reviewed the clinical outcome of 44 patients with severe neutropenia (46 cases) and underlying hematological malignancies suffering from IPA unresponsive to standard antifungal therapy. They received a total of 181 human recombinant granulocyte colony-stimulating factor (rh G-CSF) stimulated GTX at Freiburg University medical center from 1996 – 2009. Neutropenias were caused by conventional chemotherapy (n=38), conditioning chemotherapy for allogeneic (n=4) and autologous (n=2) hematopoietic cell transplantation (HCT), aplastic anemia (n=1) and by intense immunosuppressive (n=1). Donors were exclusively relatives and acquaintances of the recipients. IPA was diagnosed by clinic, computed tomography (CT) scan, serological or microbiological measures. Response of GTX was evaluated by repeated CT, decreasing C-reactive protein (CRP) levels, hematopoietic regeneration and clearance of serum galactomannan antigen. Results: A median of 3 GTX (range 1–25) containing a median total of 59.4×10⁹ (range 3–170) white blood cells per GTX were administered. All but five (3%) transfusions were well tolerated. Median duration of neutropenia proceeding GTX was 15.5 d (range 4–70). Resolution of infection or clinical improvement was achieved in 29 (63%) patients with IPA and haematopoietic recovery has been assumed within 10 days after the last GTX in 34 patients (74%). Thirty-three (72%) patients were alive one month after the first GTX. Overall, progressive malignant disease was the main cause of death. Patients not responding to GTX died without on septic complications despite appropriate antibacterial and antifungal treatment. Nine out of 26 neutropenic patients receiving GTX after conventional chemotherapy underwent allogeneic HCT later on after control of IPA. Conclusions: Rh G-CSF stimulated GTX are a safe and effective therapeutic tool for patients with hematological malignancies suffering from profound neutropenia and antifungal-therapy resistant IPA. GTX may serve as a bridging therapy in severe neutropenic patients with IPA scheduled for allo-HCT.

Bertz:GILEAD: Research Funding; MSD: Membership on an entity's Board of Directors or advisory committees.