Randomized phase III study of granulocyte transfusions in neutropenic patients

Despite antibiotics, antifungals and haematopoietic growth factors, infections remain a major threat to neutropenic patients. To determine the role of granulocyte transfusions (GTs) in anti-infective therapy during neutropenia, GT administration was randomized in 74 adults with haematological or malignant diseases, febrile neutropenia and pulmonary or soft-tissue infiltrates after conventional or high-dose chemotherapy, a majority of them after allo-SCT (n = 39). Neutrophil reconstitution was equal in the treatment and control arm. GT toxicity was minimal. The probability of 28-day survival after randomization was > 80% in both groups, and no effect of GT on survival until day 100 could be detected in patients with fungal (n = 55), bacterial or unknown infection (n = 17) and various levels of neutropenia (ANC < 500 vs >500 x 10(6)/l). These findings can be attributed primarily to procedural obstacles, such as long delay from randomization to first GT, low cell content and slow sequence of GT, difficulties in randomizing a safe and potentially life-saving treatment in severely endangered individuals, and a large proportion of rapidly recovering patients in both arms. The requirement of another trial in a more specific patient population with daily transfusions of sufficient numbers of granulocytes to support or refute the empirically acknowledged benefits of GT is discussed.