Early Granulocyte Transfusions Increase Survival Rates in Neutropenia With Multidrug-Resistant Organisms

Patients with neutropenia who have multidrug-resistant organisms have better rates of overall survival when receiving early granulocyte transfusions from healthy donors rather than receiving the transfusions later, according to a new study.

Researchers, who also found that the transfusions were well-tolerated in patients, followed patients with different hematological disorders as well as recipients of hematopoietic stem cell transplants (HSCT) who received granulocyte transfusions between January 2014 and December 2017. All patients had an absolute neutrophil count of <0.5x109/L and severe neutropenic sepsis.

The study analyzed 143 granulocyte collections for 66 infectious episodes in 60 patients who had a median age of 21 years. Multidrug-resistant organisms were observed in 47 of the 66 (71.2%) episodes and fungal infections were seen in 9 (13.6%).

“Despite modern antimicrobials and supportive therapy, bacterial and fungal infections are still major complications in patients of hematological malignancies and in recipients of HSCT with treatment-related neutropenia,” explained the researchers. “Thirteen to 60% of HSCT recipients develop blood stem infections, which are associated with 12% to 42% mortality.”

During the study period, granulocytes were transfused within 6 hours of collection over a period of 1-2 hours in adults and 2-3 hours in pediatric patients. Prior to each transfusion, patients received premedication with 15mg/kg of acetaminophen, 4mg/kg of hydrocortisone and 0.1mg/kg of chlorpheniramine maleate. To avoid hypocalcemic tetany, patients were also given 2ml/kg of calcium gluconate before, during, and at the end of transfusion.

The median duration of fever before giving granulocyte transfusions was 7 days, and the median number of transfusions given per patient was 2.

Resolution of the index infection was seen in 45 of the 66 infectious episodes, with a 30-day survival of 67.7%.

According to the researchers, 30-day survival rates were higher in patients who had granulocyte transfusions early—within 7 days of neutropenic sepsis&mdash;compared with those who received transfusions after 7 days. The researchers also observed that durations of fever and severe neutropenia were shorter in patients who received early granulocyte transfusions (18 days vs 19 days and 17 days vs 28 days, respectively).

Among the 47 infectious events due to multidrug-resistant organisms, patients in 36 of the episodes (76.6%) were successfully treated, as well 4 of the 9 patients with fungal infections. Twenty of these episodes were early granulocyte transfusions, resulting in improved survival.

The researchers noted that there was no significant difference in 30-day survival based on transfusion dosage.

“Six patients developed a mild Transfusion Related Acute Lung Injury, which would be managed conservatively, without requiring ventilator support,” explained the researchers. “One patient developed hypoalcemic tetany. Except for mild bone pains in 6 donors, requiring an analgesic drug, no other significant complications were observed in the donors during and after the granulocyte collection.”

Reference:

Garg A, Gupta A, Mishra A, Singh M, Yadav S, Nityanand S. Role of granulocyte transfusions in combatting life-threatening infections in patients with severe neutropenia: experience from a tertiary care centre in North India [published online December 27, 2018]. PLOS One. doi: doi.org/10.1371/journal.pone.0209832.