Granulocyte transfusions from G-CSF-stimulated donors for the treatment of severe infections in neutropenic pediatric patients with onco-hematological diseases

From March 1994 to January 2001, 15 courses of granulocyte transfusion (GTX) were administered to 13 neutropenic patients (6 male and 7 female patients; median age 7 years, range 3 months to 14 years) affected by: acute lymphoblastic leukemia (ALL) in 6 cases, acute myeloid leukemia (AML) in 5, very severe aplastic anemia in 1, and familial erythrophagocytic lymphohistiocytosis (FEL) in 1. Infections were classified as microbiologically defined and clinically defined infections in 8 and 7 episodes, respectively. Before the GTX transfusions, broad-spectrum antibacterial and antifungal therapy had been administered for a median of 12 (range 5-28) and 8 days (range 2-50), respectively, with no improvement. G-CSF was administered prior to GTX in 9 episodes of infection, with a median of 9 days of treatment (range 4-30). Leukapheresis was obtained from 15 related donors (father, 10; mother, 3; sister, 1; aunt, 1) after s.c. stimulation with G-CSF, 300 micro g daily, starting from day -3 (where day 0 was the day of the first granulocyte collection) and continuing throughout the period of GTX treatment. The donors' median white blood cell (WBC) count at leukapheresis was 31.6 x 10(9)/l (range 12-56), and the median yield was 31.39 x 10(9) WBC (range 2.96-64.73 x 10(9)), with a proportion of PMN of 90-95%. Overall, 70 GTX were administered, with a median of 4 GTX per episode of infection (range 2-11). The combination of GTX with antimicrobial therapy led to complete or partial recovery in 6 and in 3 of 15 episodes (60%), respectively. Priming of the donor with G-CSF was well tolerated, the most common side-effects being bone pain, malaise and paresthesia. All donors are alive and well after a median of 4.5 years (range 0.8-7.7) from donation. We conclude that GTX is potentially useful when the severity of the infection and the host's immunodeficiency make any other antimicrobial treatment ineffectual. Long-term safety data on the stimulation of donors with G-CSF have been reassuring to date. Further controlled studies are needed to assess the exact role of GTX in the outcome of neutropenic patients with severe infection and any criteria for patient selection and the timing of GTX administration.