1Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.
2Department of Hematology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Granulocyte transfusion (GTx) is performed as a supportive therapy in severe neutropenic patients caused by various conditions. The study aimed to analyze the hematologic parameters of donors, patients, and granulocyte concentrates to predict successful GTx.
This study was performed in 281 donors, with their granulocyte concentrates being collected through apheresis, and in 54 severe neutropenic patients who had various hematologic diseases. Complete blood cell counts of donors pre- and post-apheresis, granulocyte concentrates, and patients pre- and post-GTx were analyzed. Patients were divided into two groups according to survival at discharge (Group S, survival; Group D, dead) to compare various factors including age, infection status, pre- and post-GTx total white blood cell counts (TWBCC) and absolute neutrophil counts (ANC), total number of GTx, infused TWBCC and ANC per weight, and use of G-CSF during therapy.
Overall data of patients showed that both TWBCC and ANC were significantly increased after GTx (median values at pre-GTx, TWBCC=0.40×109/L, ANC=0.14×109/L; post-GTx, TWBCC=0.57×109/L, ANC=0.29×109/L, both
The TWBCC and ANC after GTx were significant factors to predict patients' outcome. Therefore, follow-up of those two parameters may be helpful to select or consider other therapeutic modalities including additional GTx.
Neutropenia may occur due to decreased granulocyte production during treatment process such as high-dose chemotherapy or hematopoietic stem cell transplantation. Severe neutropenia occurs when the absolute neutrophil count (ANC) in the peripheral blood is less than 0.5×109/L . Severe neutropenia patients often have poor prognosis. Although granulocyte transfusion (GTx) is known to be beneficial for recovery from infections and granulocytic regeneration in the bone marrow, the effect of GTx remains controversial . Moreover, clinical evidences about the indications and treatment goals in GTx are insufficient. Therefore, the present study aimed to analyze the hematologic parameters of patients, donors, and granulocyte concentrates to predict successful GTx.
The subjects of this study included 281 healthy donors who visited Seoul St. Mary's Hospital from January 2015 to June 2017 and 54 patients with hematologic diseases who underwent GTx due to severe neutropenia. These donors were selected in accordance with the domestic blood management law in South Korea . ABO and Rh-D blood types of all donors and patients were matched. For mobilization of granulocytes, 10 µg/kg of granulocyte colony-stimulating factor (G-CSF) was injected to donors subcutaneously about 12 hours before collecting granulocytes. After G-CSF administration, 650 mg of acetaminophen was administered orally when the following symptoms were present: fever, headache, muscle aches, and chills. This study received approval from the institutional review board (IRB).
Granulocytes were collected following the Mononuclear Cell (MNC) collection protocols (LRS Turbo, version 7.0) of COBE Spectra (Terumo BCT, Lakewood, CO, USA). Only anticoagulant citrate dextrose solution, solution A was mixed with blood at a ratio of 1:15. Erythrocyte sedimentation agent with concentrated citrate was not used because of domestic reason. The collection speed was 30–45 mL/min, and the volume of the total blood circulation for single collection was 5,500–7,000 mL. WBC Colorgram (Terumo BCT, Lakewood, CO, USA) set hematocrit to an approximate range between 5.0 and 7.5%. The total collection volume of granulocyte concentrates was 350 mL, and the target granulocyte count was more than 1.8×109/unit according to the national standard guideline of blood centers. Collected granulocytes were irradiated with gamma rays of 25 Gy from a cesium source and were stored at room temperature.
We measured donors' total white blood cell count (TWBCC) before and after G-CSF administration and donors' ANC after G-CSF administration. General characteristics including gender, age, height, and weight were also analyzed. For granulocyte concentrates, TWBCC and ANC were measured. Patients' TWBCC and ANC before and after GTx, number of transfusions, and total infused TWBCC and ANC were measured. The performance of G-CSF for patients was also reviewed to analyze its effect. Clinical characteristics of patients including gender, age, weight, diagnosis, neutropenic cause, infection status, and survival at discharge were also analyzed.
Pearson's correlation analysis was performed for TWBCC before and after G-CSF administration of donors and for TWBCC and ANC of donors and granulocyte concentrates after G-CSF administration. In this study, we divided patients into “Group S” for surviving patients and “Group D” for dead patients based on their survival at discharge. Various parameters of these two groups were compared using Mann-Whitney U test or Fischer's exact test. A
Among the 281 granulocyte donors, 270 (96.1%) donors were males and 11 (3.9%) donors were females, respectively. Their mean age, height, and body weight were 28.3±7.7 years, 174.1±5.9 cm, and 71.6±9.5 kg, respectively. The mean TWBCC values of donors before and after G-CSF administration were 6.30±1.34×109/L and 24.40±4.41×109/L, respectively. ANC was measured only after G-CSF administration, with a mean value of 22.39±4.24×109/L. The mean values of TWBCC and ANC of granulocyte concentrates were 73.78±23.41×109/L and 49.02±24.88×109/L, respectively (Table 1). Donors' TWBCC and ANC showed significant correlation before and after G-CSF administration (
Among the 54 patients, 28 (51.9%) were males and 26 (48.1%) were females, respectively. Their mean age was 46.7±16.4 years. Regarding the diagnosis, acute myeloid leukemia was the most common (43, 79.6%) one, followed by aplastic anemia (4, 7.4%) and acute lymphoblastic leukemia (3, 5.6%). Additionally, mixed phenotype acute leukemia, myelodysplastic syndrome, essential thrombocytosis, and hemophagocytic lymphohistiocytosis each had one (1.9%) case. All patients were suffering from neutropenia (ANC<0.5× 109/L), which was caused by chemotherapy (42 patients, 77.8%), hematopoietic stem cell transplantation (4 patients, 7.4%), or others (8 patients, 6.8%). The mean initial values of TWBCC and ANC were 0.41×109/L and 0.16×109/L, respectively. After GTx, they were significantly increased to 0.58×109/L and 0.29×109/L, respectively (Table 2).
Twenty-five (46.3%) patients belonged to “Group S,” while 29 (53.7%) patients belonged to “Group D,” respectively. Age, gender, underlying disorder, cause of neutropenia, and infection status at enrollment were compared between the two groups. There were no significant differences in indicators mentioned above (Table 3). Variables associated with response to GTx were analyzed including the following: G-CSF, TWBCC, ANC, the frequency of GTx, and total infused TWBCC and ANC per kilogram. Among these parameters, TWBCC (
There were no significant correlations between TWBCC after GTx and patients' age (
In this study, 10 µg/kg of G-CSF was administered to donors for stimulation. The mean value of TWBCC in each donor after G-CSF administration was increased four times from 6.3×109/L to 24.4×109/L. According to the donors' TWBCC increment after GSF-administration, it also correlated with the TWBCC of their apheresis granulocyte concentrates. We could obtain granulocyte concentrates at an average TWBCC of 73.78×109/L. It is generally known that when granulocyte collection is performed using 5–10 µg/kg of G-CSF, it is possible to obtain granulocyte concentrates at an average of 40–60×109/L . Our results exceeded those of the previous studies.
In this retrospective analysis performed on 54 patients with hematologic diseases, chemotherapy was the most common cause of neutropenia (42 people, 77.8%), followed by hematopoietic stem cell transplantation (7 people, 7.4%). This is similar to a previous study showing that chemotherapy is the most common cause of decreased neutrophil counts in the majority (73–80%) of cases .
In average, a total of 73.8×109/L granulocytes were transfused, and ANCs were significantly increased as much as 0.59×109/L. This increment is lower than that reported in the previous studies which showed increase of approximately 0.6–2.6×109/L of ANCs after an average GTx of 40–80×109/L . A domestic study has also reported that with an average transfused granulocyte count of approximately 50×109/L, neutrophil counts are increased to 1.0×109/L in 84% of cases . This percentage is higher than that (37%, 20/54) in the present study. Considering that several studies have reported various levels of increase in neutrophil counts, features of patient groups and treatment modalities other than GTx might have affected the degree of granulocyte increase.
We analyzed the effect of GTx based on the mortality at discharge. In this study, 46.3% of patients survived to hospital discharge, suggesting that GTx is a helpful supportive therapy in severe neutropenic patients. When we compared factors between “Group S” and “Group D” after treatment with GTx, TWBCC (