A child is admitted with a serious infection. After two days of antibiotics, he is severely neutropenic. The physician orders granulocyte transfusions for the next four days. The mother asks the nurse why? The nurse responds:
A. “This is the only treatment left to offer the child.”
B. “This therapy is fast and reliable in treating infections in children.”
C. “The physician will have to explain his rationale to you.”
D. “Granulocyte transfusions replenish the low white blood cells until the body can produce its own.”
Correct Answer: D. “Granulocyte transfusions replenish the low white blood cells until the body can produce its own.”
Granulocyte (neutrophil) replacement therapy is given until the patient’s blood values are normal and he is able to fight the infection himself. Options 1 and 3 are not therapeutic responses. The usual method to obtain granulocytes for transfusion in the US is by single-donor apheresis (intermittent or continuous centrifugation leukapheresis, using an agent like dextran or heptastarch to facilitate separation of the red blood cells). An adult therapeutic dose of granulocytes obtained by apheresis contains between 1.5 x 108 and 3 x 108 granulocytes/kg body weight of the designated recipient
Option A: Transfused granulocytes have activity against infectious agents, but may cause transfusion reactions (including severe, even fatal, pulmonary reactions), alloimmunization that could contribute to the rejection of a subsequent HCT, and (unless they are obtained from CMV-seronegative donors) CMV infection. Regarding prevention of infection, there is enough (low quality, but consistent) evidence to suggest that prophylactic GTX (granulocyte transfusions) may result in decreased infection, but there is no evidence they would be better than prophylactic antimicrobials, and overall survival has never been affected.
Option B: The treatment in option 2 takes days and is not always able to prevent morbidity and mortality. there are a few reports that are compelling enough to believe that this intervention may be life-saving under some circumstances, which means centers that take care of patients with prolonged neutropenia should at least consider GTXs. The technical aspects of the procedure must be carefully implemented: obtaining the largest amount of granulocytes, transfusing them within 8 hours, and aiming for an ANC increase in the 500–1000/?L should be minimum goals.
Option C: Regarding the therapeutic use of GTX for established infections, all modern controlled studies have failed to show clinical benefit. The negative result of the RING study is particularly troublesome because it is difficult to envision how it could have been modified to provide a more definitive answer. Although it is possible, as the authors suggested and some experts have argued, that there was indeed an effect (limited to the patients who received large doses of granulocytes) but the study could not demonstrate it due to lack of power, the simpler explanation is that GTXs, given to the patient population identified by the inclusion criteria of the RING study, do not add any benefit to optimal antimicrobial treatment.