Repeated Transfusion of Granulocytes to Control Multidrug-Resistant Pseudomonas Aeruginosa Sepsis in Haploidentical Hematopoietic Stem Cell Transplant Patients during Pre-Engraftment Stage

Background and Objectives: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative therapy for treating pediatric hematological malignancies that are refractory to other therapies. However, severe infections in neutropenic patients remain the major cause of morbidity and mortality, as well as influence the engraftment during HSCT. Multidrug-resistance (MDR) pseudomonas aeruginosa sepsis during the pre-engraftment stage has a highly prevalence of mortality, especially in patients with the primary infection site at the facial dangerous triangle. Without the efficient and time treatment, the bacterium may readily spread into the brain, causing severe intracranial infection and even death. There is an urgent need to effectively control MDR-pseudomonas aeruginosa infection and reduce the mortality of patients undergoing allo-HSCT.

Method: We report herein a 5-year-old boy with acquired severe aplastic anemia (SAA) who experienced a secondary engraftment failure eight months after receiving haploidentical HSCT from his father. Owing to recurrent fever and severe pneumonia during persistent neutropenia, the patient received second transplant using bone marrow cells from his farther. Two days after the secondary transplant bloodstream identified an infection of MDR-pseudomonas aeruginosa accompanied with symptoms of chills and high fever, and deteriorating pneumonia. On day +4 he had a cellulitis at facial dangerous triangle with lacrimal gland and nasolacrimal duct involved, and secretion culture also confirmed the same bacteria. He was given antibiotics of Tetracycline, Levofloxacin, and Cefoperazone schubatam. However, the involved skin became worse and high fever peak became more frequent, suggesting the progression of sepsis. To facilitate the reconstitution of granulocytes in the patient, we performed six doses of granulocyte transfusion (GTX) from father once every over a period of six days. Granulocyte counts were performed every 12 hours after transfusion in order to maintain a level of granulocyte more than 0.5×109/L. Blood typing showed that the patient was type A and the farther was type AB. To avoid a possible hemolysis due to ABO-mismatched, we treated granulocytes with hydroxyethyl starch before transfusion.

Results: During GTXs (from day +6 to +11 after transfusion), the patient's body temperature fluctuated between 37.0℃-38.2℃. There were no signs and symptoms of exacerbated pneumonia, such as cough, hemoptysis and moist rale. We didn't observe transfusion related acute lung injury (TRALI) and respiratory failure. The urine was clear without hematuria. The area of skin involved became under control. Notably, the patient had granulocyte engrafted on day +15 after transfusion, decrease of body temperature on day +16 and normal temperature on day +20. Concurrently, the facial cellulitis was gradually narrowing and moist rale of the lung disappeared. A repeat chest CT scan confirmed disappearance of the infection site in the lung. The bloodstream culture was negative on day +9 and secretion culture was negative on day +15. We maintained the treatment with antibiotics until the negative blood culture was confirmed twice. Eleven months after the treatment, the patient is alive with full donor chimaerism. His blood type becomes AB type. Other tests, including peripheral blood cell counts, liver and renal functions as well as pulmonary function, are all normal.

Conclusion: Multidrug-resistant bacteria infection is a common and yet fatal complication in SAA patients. These patients usually experience a prolonged period of neutropenia when undergoing HSCT. We demonstrate here that when being combined with the utilization of broad spectrum antibiotics, repeated GTXs from donor source prove to be an effective therapy for controlling these infections, thereby reducing early death and improving successful rate of allo-HSCT. Therefore, GTXs are recommended as, at best, a "bridge" procedure, that may protect the patient from fatal infections until myeloid recovery ensues