Neutrophil (Granulocyte) Transfusions

Chapter 466 Neutrophil (Granulocyte) Transfusions

Guidelines for granulocyte transfusion (GTX) are listed in Table 466-1 on the Nelson Textbook of Pediatrics website at www.expertconsult.com. Although GTX has been used sparingly in the past, the ability to collect markedly higher numbers of neutrophils from donors stimulated with recombinant granulocyte colony-stimulating factor (G-CSF) plus dexamethasone has led to renewed interest, particularly for recipients of hematopoietic progenitor cell transplantation. GTX should be reconsidered at institutions where neutropenic patients continue to die of progressive bacterial and fungal infections or to suffer substantial morbidity despite the optimal use of antimicrobial agents (i.e., “antibiotics”) and recombinant myeloid growth factors.

The role of GTX added to antibiotics for patients with severe neutropenia (blood neutrophil count <0.5 × 10⁹/L) due to bone marrow failure is similar for adults and children. Infected neutropenic patients usually show response to antibiotics alone, provided that bone marrow function recovers early during the infection. Because children with newly diagnosed leukemia show rapid response to induction chemotherapy, they are rarely candidates for GTX. In contrast, infected children with sustained bone marrow failure (malignant neoplasms resistant to treatment, aplastic anemia, and hematopoietic progenitor cell transplant recipients) may benefit when GTX is added to antibiotics. The efficacy of GTX for bacterial sepsis unresponsive to antibiotics in patients with severe neutropenia (blood neutrophil count <0.5 × 10⁹/L) is supported by many controlled studies, whereas GTX’s efficacy for yeast and fungal infections remains unproven despite some encouraging reports.

Children with qualitative neutrophil defects (neutrophil dysfunction) usually have adequate numbers of blood neutrophils but are susceptible to serious infections, because their cells kill pathogenic microorganisms inefficiently. Neutrophil dysfunction syndromes are rare, and no definitive studies have established the efficacy of GTX. However, several patients with progressive life-threatening infections have shown striking improvement with the addition of GTX to antimicrobial therapy. These disorders are chronic, and because of the risk of inducing alloimmunization, GTX is recommended only when serious infections are clearly unresponsive to antimicrobial drugs.

Neonates are unusually susceptible to severe bacterial infections, and a number of defects of neonatal body defenses may be contributing factors. These abnormalities are accentuated in sick premature neonates, and it is logical to consider GTX. Neonates exhibiting fulminant sepsis, relative neutropenia (blood neutrophil count < 3.0 × 10⁹/L during the 1st wk of life and < 1.0 × 10⁹/L thereafter), and a severely diminished neutrophil marrow storage pool (with < 10% of nucleated marrow cells postmitotic neutrophils) are at particularly great risk of dying if treated only with antibiotics. Although some studies have shown a significant benefit from GTX, it is rarely used today because it is difficult to obtain in a timely fashion. Instead, some neonatologists consider alternative therapies, including IV immunoglobulin and recombinant myeloid growth factors (G-CSF or granulocyte-macrophage colony-stimulating factor [GM-CSF]). Results of studies evaluating IV immunoglobulin have been mixed, but a meta-analysis found significant benefit for neonates with proven sepsis. Current data are insufficient to determine whether recombinant myeloid growth factors have a role in treating these neonates, despite the fact that both G-CSF and GM-CSF have been demonstrated to enhance myelopoiesis and raise neutrophil counts in infants. Importantly, G-CSF is efficacious for the long-term treatment of several types of severe congenital neutropenia.

Once the decision to provide GTX has been made, an adequate dose of fresh leukapheresis cells must be transfused. Neonates and infants weighing < 10 kg should receive 1-2 × 10⁹/kg neutrophils per GTX. Larger infants and children should receive a total dose of at least 1 × 10¹⁰ neutrophils per GTX; the preferred dose for adolescents is 5-8 × 10¹⁰ per GTX, a dose requiring donors to be stimulated with G-CSF plus dexamethasone. GTX should be given daily until either the infection resolves or the blood neutrophil count is sustained above 1.0 × 10⁹/L for a few days.