Granulocyte Transfusion
Granulocyte transfusions are usually ordered for patients with hematologic malignancies and absolute neutropenia who have a bacterial or fungal infection that is not responding to appropriate antimicrobial therapy. Recipients should meet the following criteria:
- Granulocyte count of <500/uL
- Clear evidence of a bacterial or fungal infection
- Inadequate response to definitive antimicrobial therapy
Most recipients have a hematologic malignancy being treated with aggressive chemotherapy and /or undergone hematopoietic stem cell transplant. Recipients not expected to recover marrow function generally should not be considered candidates for granulocyte transfusion.
Granulocyte transfusions may also be ordered for neonates with sepsis, who develop neutropenia from storage pool depletion. Evidence for their efficacy in this setting is of low quality.
The Resolving Infection in Neutropenia with Granulocytes (RING) study was a 5-year (2008-2013) randomized controlled trial sponsored by the NHLBI Transfusion Medicine/Hemostasis Clinical Trials Network. Subjects with severe neutropenia (ANC< 500/mL) and bacterial and/or fungal infections were randomized to two groups. One group received standard antimicrobial therapy alone, while the second group received standard antimicrobial therapy in combination with daily granulocyte transfusions from donors stimulated with granulocyte colony stimulating factor (G-CSF) and dexamethasone.
The study's dose of granulocytes (40 x 109 granulocytes/unit) was four times higher than the dose required by AABB Clinical Standards (10 x 109 granulocytes/unit). Primary endpoints were overall survival and response to infection at 42 days. Investigators were unable to detect statistical differences in antimicrobial response rates or overall survival between arms. Post hoc secondary analyses suggested that higher doses were effective. The efficacy of granulocyte transfusion remains unknown.
Granulocytes are collected from a single donor by apheresis. The donor is stimulated the day before collection with an injection of granulocyte colony stimulating factor (G-CSF) and an oral dose of dexamethasone. Stimulation increases the yield of granulocytes collected to 4.0 x 1010 granulocytes or more. Collection by apheresis generally takes 2.5 to 3 hours; during which 7 to 10 liters of whole blood are processed. G-CSF stimulated donors often experience self-limited headache, arthralgia, bone pain, fatigue and difficulty sleeping.
Because of their short shelf life, granulocytes are usually issued before infectious disease testing is completed. For this reason, granulocytes are usually collected from apheresis platelet donors who have tested negative in the past 30 days.
Granulocytes are not licensed by the Food and Drug Administration (FDA). They should be stored at room temperature without agitation. The final volume including anticoagulants and residual plasma is 200 to 300 mL. Granulocytes contain between 20 and 50 mL of red blood cells. Therefore, they must be ABO and crossmatch compatible with the recipient. If the intended recipient has an alloantibody, the granulocyte must be collected from a donor, whose red blood cells are negative for the corresponding antigen.
Granulocytes must be irradiated to prevent transfusion-associated graft versus host disease. Patients who are CMV negative need to receive granulocytes from a CMV negative donor. If the recipient has HLA antibodies, granulocytes should be collected from a donor who is HLA compatible.
The typical life span of a granulocyte is approximately 8 hours. Granulocytes collected from G-CSF and steroid stimulated donors may have an increased life span up to 24 hours. AABB Standards indicate that granulocytes expire within 24 hours. Ideally, granulocytes should be given as soon as processing and irradiation have been completed. They should be transfused using a standard blood infusion set. Granulocytes should not be transfused through a leukocyte reduction filter or a microaggregate filter.
Granulocyte transfusions cause adverse reactions such as fever, chills and hives in up to 50% of recipients. More seriously, transfused granulocytes may be sequestered in pulmonary capillaries causing transfusion related acute lung injury (TRALI). Alloimmunization to HLA and HNA antigens can occur and complicate future transfusions.
Granulocyte transfusions are usually continued on a daily basis for five to seven days, until the recipient's granulocyte count recovers to >500/uL. Recipient's granulocyte count should be monitored before and after each transfusion. The decision to discontinue granulocyte transfusions is based on the recipient's granulocyte count and resolution of infection.
References
Price, TH et al. Efficacy of transfusion with granulocytes from G-CSF/dexamethosone-treated donors in neutropenic patients with infection. Blood. 2015. 126:2153-61.
Cancellas JA. Granulocyte transfusion: questions remain. Blood. 2015. 126:2082-3.
