Principles of Neutrophil (Granulocyte) Transfusions

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Chapter 51 Principles of Neutrophil (Granulocyte) Transfusions

Ronald G. Strauss

Table 51-1 Infectious Problems in Neutropenic Patients Treated With Historical Granulocyte Transfusions in 34 Studies

Collection and Transfusion of Neutrophil Concentrates

To ensure adequate numbers and quality of polymorphonuclear neutrophils (PMNs) for transfusion, PMNs must be collected from stimulated donors by automated leukapheresis using an erythrocyte sedimenting agent, such as hydroxyethyl starch. A major limitation of granulocyte transfusion (GTX) efficacy has been the inability to transfuse adequate numbers of perfectly functioning PMNs. Under the stress of a severe bacterial infection, the marrow of an otherwise healthy adult will produce between 10¹¹ and 10¹² PMNs in 24 hours. Granulocyte concentrates collected from healthy donors who are not stimulated with corticosteroids or granulocyte colony-stimulating factor (G-CSF) will contain between 0.2 and 0.8 × 10¹⁰ PMNs—a woeful number equal to approximately 1% of a healthy marrow’s output. Hence donor stimulation is mandatory to achieve even a hope of a reasonable PMN dose per GTX.

Donor stimulation using only properly timed corticosteroids (≥24 hours before leukapheresis, NOT immediately before) will increase the yield to approximately 2 × 10¹⁰ PMNs. Stimulation with G-CSF, alone or in combination with corticosteroids, will produce higher but variable PMN yields. Yields of 4 to 8 × 10¹⁰ PMNs are achieved regularly, and posttransfusion blood PMN counts frequently increase to 1 to 3 × 10⁹/L, with PMNs detected in the recipient’s bloodstream for several hours after GTX. Currently PMN donors are optimally stimulated using 300 to 480 mcg G-CSF given subcutaneously plus 8 mg dexamethasone taken orally approximately 12 hours before beginning leukapheresis.¹ Recent reports suggest that adrenal corticosteroids might cause posterior subcapsular cataracts in PMN donors. Although these reports are not in total agreement, it seems logical to include this cautionary information in donor consent forms or to stimulate PMN donors using only G-CSF—accepting lower PMN doses with the last option.²

Each institution must assess local needs. If, despite optimal antimicrobial and other supportive therapy, neutropenic patients suffer significant morbidity or mortality from infections, GTX should be considered. Once therapeutic transfusions have been prescribed, they must be given effectively (≥2 × 10¹⁰ PMNs per dose with corticosteroid stimulation, ≥4 × 10¹⁰ PMNs per dose with G-CSF, and never <1 × 10¹⁰ PMNs per dose). Transfusions are continued until the infection has resolved or until blood PMNs have risen above 1.0 × 10⁹/L in the absence of further GTX. It seems logical that patients with evidence of alloimmunization (platelet refractoriness, leukocyte antibodies, repeated febrile transfusion reactions, or posttransfusion pulmonary infiltrates) should receive GTX collected from donors selected to be leukocyte compatible by human leukocyte antigen matching and/or leukocyte crossmatching. However, it has not been clearly shown that attempts to improve leukocyte antigen compatibility do in fact increase the success of GTX in alloimmunized patients—particularly when modern GTX from G-CSF–stimulated donors are transfused. Granulocyte concentrates should be transfused as soon as possible after collection because PMN functions begin to deteriorate rapidly. Some delay between collection and transfusion is inevitable, and granulocyte concentrates are usually stored briefly at 22° C, with little or no agitation. It is highly desirable to transfuse granulocyte concentrates within 6 hours of collection; they should not be given if more than 24 hours old.

Author’s Approach to Therapeutic Granulocyte Transfusions

Indicated for severe bacterial, yeast, or fungal infection in a neutropenic patient (<0.5 × 10⁹ polymorphonuclear neutrophils [PMNs]/µL blood) when the infection progresses despite optimal antimicrobial therapy.

Collect PMNs (4 to 8 × 10¹⁰) from allogeneic blood donors, as follows:

1. Stimulate neutrophilia by giving the donor 300 to 480 mcg of granulocyte colony-stimulating factor (G-CSF) subcutaneously 12 hours before beginning leukapheresis, with or without 8 mg dexamethasone orally 12 hours before beginning leukapheresis.

2. Process 10 L of donor blood using a continuous-flow blood separator with citrated hydroxyethyl starch solution infused throughout the collection.

Transfuse one granulocyte concentrate (4 to 8 × 10¹⁰ PMNs) daily until bone marrow recovery (blood PMNs >1.0 × 10⁹/L without granulocyte transfusion) or clinical resolution of infection.

1 Clarke K, Szer J, Shelton M, et al. Multiple granulocyte transfusions facilitating unrelated bone marrow transplantation in a patient with very severe aplastic anemia complicated by suspected fungal infection. Bone Marrow Transplant. 1995;16:723.

2 Hester JP, Dignani MC, Anaissie EJ, et al. Collection and transfusion of granulocyte concentrates from donors primed with granulocyte stimulating factor and response of myelosuppressed patients with established infection. J Clin Apheresis. 1995;10:188.

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