Clinical Efficacy and Tolerability of Granulocyte Transfusions for the Treatment of Febrile Neutropenia in the Patients with Hematologic Malignancies.

Bacterial or fungal infections in prolonged neutropenia are related to high mortality in patients with hematologic malignancies despite vigorous antibiotic and antifungal treatment. Granulocytes transfusions (GTs) have been used as an adjunctive to improve survival. However, the efficacy and safety of GTs are still controversial and reliable prognostic factors remain to be defined. This study aims to evaluate the clinical efficacy and tolerability of GTs and to assess the prognostic factors associated with survival outcome in the patients with neutropenia and severe infection.

This study used prospectively collected comprehensive database, institutional leukapheresis registry. Adult patients (18 ≥ years) with hematologic malignancies who had received at least 3 times of GTs in each episode of febrile neutropenia (absolute neutrophil count < 0.5 × 10⁹/L) were eligible.

Between Jan 2004 and Jun 2009, a total of 892 GTs in 119 episodes of 112 patients were identified. The median age was 45 years (range: 18 to 90 years). Primary diagnosis was acute leukemia (n = 87, 73.1%), lymphoma (n = 17, 14.3%), aplastic anemia (n = 9, 7.6%), myelodysplastic syndrome (n = 3, 2.5%), and multiple myeloma (n = 3, 2.5%). The cause of neutropenia was conventional chemotherapy (n = 95, 79.8%), stem cell transplantation (n = 12, 10.1%), and primary disease itself (n = 12, 10.1%). Microorganisms were isolated from blood culture in 54 episodes (53.8%). Isolated organisms were single species of bacteria (n = 40, 33.6%), multiple species of bacteria (n = 19, 16.0%), and fungus with bacteria (n = 5, 4.2%). Fifty-six episodes (47.1%) were under use of vasopressors, and 25 episodes (21.0%) were treated an in intensive care unit. The median time from initiation of neutropenia to start of GTs was 18 days (range: 1 to 645 days). The median of 6 GTs per episode (range: 3 to 38) were administered, containing a median total of 36.65×10¹⁰ leukocytes per episode. Control of infection was achieved in 57 episodes (47.9%). The 28-day and 100-day survival rate was 64.2±0.04% and 23.4±0.04%, respectively. Adverse reactions were tolerable including fever (n = 29, 24.4%), rigor (n = 9, 7.6%), hypotension (n = 9, 7.6%), and rash (n = 3, 2.5%). Life-threatening respiratory complications were rare including massive hemoptysis (n = 6, 5.0%) and respiratory failure (n = 6, 5.0%). Planned GTs could not be completed in 5 episodes (4.2%) due to intolerability. In a univariate analysis, episodes after stem cell transplantation were significantly related to worse survival (median 32 vs 111 days, P = 0.005); 11 out of 12 stem cell transplanted patients died within 100-days. Additionally, elderly cases (≥ 65 years) showed tendency to have worse survival (median 21 vs 90 days; P = 0.053).

Granulocyte transfusions are tolerable and efficacious option for the treatment of infectious complications during prolonged neutropenia. Old age, previous stem cell transplantation should be considered as a poor prognostic marker for survival.

No relevant conflicts of interest to declare.