OBJECTIVE: To analyze and compare the effects of leukapheresis on hemostatic function in patients with hyperleukocytic leukemia. METHODS: A total of 139 patients with AML, ALL and CML who underwent leukapheresis from June 2009 to February 2020 and did coagulation test before and after operation were included in this study. The clearance efficiency of each group and the difference among three groups were evaluated, as well as hemostatic function including platelet counts, coagulation indicators, CDSS score and incidence of adverse events. The difference of hemostatic function caused by leukapheresis in different leukemia patients were compared. RESULTS: After leukapheresis, the WBC counts were decreased significantly in the three groups of patients (P<0.001), and the clearance efficiency was highest in ALL patients. However, the platelet counts also were decreased significantly (AML:P＜0.001, ALL: P＜0.001, CML: P＜0.01) in the three groups of patients, particularly for acute leukemia patients with a positive correlation with WBC clearance efficiency(r=0.284). After leukapheresis, fibrinogen decreased, PT and APTT prolonged. For acute leukemia patients, higher CDSS score was related to an elevated incidence of bleeding events (P<0.05). CONCLUSION Leukapheresis is an effective method to decrease the leukemic burden, but it is necessary to monitor the impact on hemostatic function. It is recommended to assess the CDSS socre for acute leukemia patients, in order to identify the predictive value for bleedings.
Acute Disease ; Blood Coagulation ; Blood Coagulation Tests ; Hemorrhage ; Hemostatics ; Humans ; Leukapheresis/methods* ; Leukemia, Myeloid, Acute/therapy*

OBJECTIVE: To improve the collection efficiency of leukapheresis, explore relatively scientific and objective evaluation indicators for collection effect, and observe the effect of high-volume leukapheresis on blood cells and coagulation function. METHODS: A total of 158 times of high-volume leukapheresis were performed on 93 patients with hyperleukocytic leukemia by using continuous flow centrifugal blood component separator. 1/5-1/4 of total blood volume of the patients was taken as the target value of leukocyte suspension for single treatment. In addition, the total number of white blood cells (WBCs) subtracted, value of WBCs reduction, rate of WBCs reduction, decrease value of WBCs count, decrease rate of WBCs count, amount of hemoglobin (Hb) lost, value of Hb lost, decreased value of Hb, total number of platelet (PLT) lost, the value of PLT loss, and decrease value of PLT count were used to comprehensively evaluate the collection effect of leukapheresis and influence on Hb level and PLT count of the patients. The prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time (TT), and fibrinogen (Fib) concentration were detected before and after treatment, and the effect of leukapheresis on coagulation function of the patients was observed. RESULTS: The volume of leukocyte suspension collected in a single treatment was 793.01±214.23 ml, the total number of WBCs subtracted was 353.25 (241.99-547.28)×10⁹, the value of WBCs reduction was 86.98 (63.05-143.43)×10⁹/L, the rate of WBCs reduction was 44.24 (28.37-70.48)%, decrease value of WBCs count was 65.73 (37.17-103.97)×10⁹/L, decrease rate of WBCs count was (35.67±23.08)%, the amount of Hb lost was 17.36 (12.12-24.94) g, the value of Hb lost was 4.31 (3.01-6.12) g/L, decreased value of Hb was 4.80 (-1.25-9.33) g/L, total number of PLT lost was 222.79 (67.03-578.31)×10⁹, the value of PLT loss was 54.45 (17.29-139.08)×10⁹/L, and decrease value of PLT count was 26.00 (8.38-62.50)×10⁹/L. Before and after a single treatment, the PT was 14.80 (13.20-16.98) s and 15.20 (13.08-16.90) s (z=-1.520, P>0.05), the aPTT was 35.20 (28.68-39.75) s and 35.40 (28.00-39.75) s (z=-2.058, P<0.05), the TT was 17.50 (16.30-18.80) s and 17.70 (16.70-19.10) s (z=-3.928, P<0.001), and the Fib concentration was 2.87±1.13 g/L and 2.64±1.03 g/L (t=7.151, P<0.001), respectively. CONCLUSION High-volume leukapheresis can improve the efficiency of leukapheresis while maintaining the relative stability of the patients' circulating blood volume. The degree of influence on the patients' Hb level, PLT count, Fib concentration, and comprehensive coagulation indicators reflecting the patients' intrinsic and cxtrinsic coagulation activity is within the body's compensation range.
Blood Coagulation Tests ; Fibrinogen ; Hemoglobins ; Humans ; Leukapheresis ; Leukemia

White blood cells (WBCs) and storage period are the main factors of transfusion reactions. In the present study, cytokine/chemokine concentrations after leukoreduction (LR) and irradiation (IR) in stored canine whole blood were measured. Red blood cell storage lesion caused by IR and LR were also compared. Blood samples from 10 healthy Beagles were divided into four groups (no treatment, LR-, IR-, and LR + IR-treated). Leukocytes were removed by filtration in the LR group and gamma radiation (25 Gy) was applied in the IR group. Immunologic factors (WBCs, interleukin-6 [IL-6], C-X-C motif chemokine ligand 8 [CXCL-8], and tumor necrosis factor-alpha) and storage lesion factors (blood pH, potassium, and hemolysis) were evaluated on storage days 0, 7, 14, 21, and 28. Compared to the treated groups, IL-6 and CXCL-8 concentrations during storage were significantly higher in the control (no treatment) group. LR did not show changes in cytokine/chemokine concentrations, and storage lesion presence was relatively mild. IR significantly increased CXCL-8 after 14 days of storage, but IR of leukoreduced blood did not increase CXCL-8 during 28 days of storage. Storage lesions such as hemolysis, increased potassium, and low pH were observed 7 days after IR and storage of blood, regardless of LR. IR of leukoreduced blood is beneficial to avoid immune reactions; however, storage lesions should be considered upon storage.
Blood Preservation ; Down-Regulation ; Erythrocytes ; Filtration ; Gamma Rays ; Hemolysis ; Hydrogen-Ion Concentration ; Immunologic Factors ; Interleukin-6 ; Leukocyte Reduction Procedures ; Leukocytes ; Necrosis ; Potassium ; Transfusion Reaction

BACKGROUND: It is very important to accurately enumerate CD34-positive (CD34+) cells for successful hematopoietic stem cell transplantation (HSCT). We evaluated the ability of the newly developed image based-immunofluorescence cell counter ADAMII (NanoEntek, Seoul, Korea) to enumerate CD34+ cells, which was improved through simultaneous CD45 analysis. METHODS: We enumerated CD34+ cells with ADAMII using 19 peripheral blood (PB) and 91 leukapheresis samples from HSCT donors. Analytical performance, including precision and linearity, was analyzed, and sample stability during storage was evaluated. Viable CD34+ cell count (vCD34) and viable CD45+ cell count (vCD45) and the percentage of viable CD34+ cells among viable CD45+ cells (CD34/CD45) as measured by ADAMII were compared with the corresponding values from two flow cytometry assays, using regression analysis. RESULTS: ADAMII demonstrated acceptable precision, as CV values of vCD34 from six samples with different counts were all < 10% (range: 3.49–9.51%). CV values of the vCD45 and CD34/45 ranged from 4.03% to 9.67% and from 2.48% to 10.07%, respectively. The linearity of vCD34 showed an excellent R 2 value (0.99) when analyzed using the intended count and flow cytometry data. The ADAMII and two flow cytometry-based assays generated very similar data for the PB and leukapheresis samples. CONCLUSIONS: ADAMII demonstrated excellent performance for use as a routine clinical assay in terms of CD34+ cell enumeration from PB and leukapheresis samples. Moreover, it could be used as a point-of-care-test for determining mobilization time and predicting an adequate apheresis stem cell product.
Blood Component Removal ; Cell Count ; Flow Cytometry ; Fluorescence ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukapheresis ; Seoul ; Stem Cells ; Tissue Donors

Hyperleukocytosis (HL), defined by a peripheral white blood cell (WBC) count exceeding 100,000/mm³, is occasionally observed in childhood acute leukemia. The increased viscosity in the micro-circulation by HL and the interaction between the leukemic blasts and endometrium of blood vessels sometimes result in leukostasis. Leukostasis can incur life-threatening manifestations, such as respiratory distress, brain infarction and hemorrhage, and renal failure, needing an emergency care. Although early stage of leukostasis is difficult to detect due to nonspecific manifestations, an emergency care is mandatory because leukostasis can proceed to a fatal course. Initial management includes an aggressive fluid therapy that can reduce WBC count, and prevent other metabolic complications implicated by HL. Packed red blood cells should be judiciously transfused because it increases blood viscosity. Conversely, transfusion of platelet concentrates or fresh frozen plasma, which does not affect blood viscosity, is recommended for prevention of hemorrhage. To reduce tumor burden, leukapheresis or exchange transfusion is commonly performed. However, the efficacy is still controversial, and technical problems are present. Leukapheresis or exchange transfusion is recommended if WBC count is 200,000–300,000/mm³ or more, especially in acute myelocytic leukemia, or manifestations of leukostasis are present. In addition, early chemotherapy is the definite treatment of leukostasis.
Blood Platelets ; Blood Vessels ; Blood Viscosity ; Brain Infarction ; Disease Management ; Drug Therapy ; Emergencies ; Emergency Medical Services ; Emergency Service, Hospital ; Endometrium ; Erythrocytes ; Female ; Fluid Therapy ; Hemorrhage ; Leukapheresis ; Leukemia ; Leukemia, Myeloid, Acute ; Leukocyte Disorders ; Leukocytes ; Leukocytosis ; Leukostasis ; Plasma ; Renal Insufficiency ; Tumor Burden ; Viscosity

BACKGROUND: Cell adhesion molecules (CAMs) expressed on hematopoietic progenitor cells (HPCs), endothelial cells, and stromal cells play a pivotal role in the mobilization of CD34+ cells. Herein, we conducted a non-randomized peripheral blood stem cell (PBSC) mobilization study aimed to compare the potential differences in the expressions of several CAMs and chemokines on CD34+ cells obtained from bone marrow aspirate before and after HPC mobilization from patients with hematologic malignancies and healthy donors. METHODS: Three-color cytofluorometric analysis was used to compare the expressions of CAMs and chemokines in the bone marrow before and after mobilization. RESULTS: For all studied groups, CAM expression among those with good and poor yields of CD34+ cells was significantly correlated with VCAM-1 (P=0.007), CD44 (P=0.027), and VLA-4 (P=0.014) expressions. VCAM-1 (P=0.001), FLT-3 (P=0.001), CD44 (P=0.011), VLA-4 (P=0.001), and LFA-1 (P=0.001) expressions were higher before HPC mobilization than after HPC mobilization. By contrast, the expression of CXCR4 significantly varied before and after mobilization only among those with successful PBSC mobilization (P=0.002). CONCLUSION: We attempted to identify particular aspects of CAMs involved in CD34+ cell mobilization, which is a highly complex mechanism that involves adhesion molecules and matrix metalloproteases. The mechanism by which CD34+ cell mobilization is activated through proteolytic enzymes is not fully understood. We believe that CXCR4, VLA-4, CD44, and VCAM-1 are the most important molecules implicated in HPC mobilization, particularly because they show a correlation with the yield of CD34+ cells collected via large volume leukapheresis.
Bone Marrow* ; Cell Adhesion Molecules ; Chemokines ; Endothelial Cells ; Hematologic Neoplasms ; Hematopoietic Stem Cells ; Humans ; Integrin alpha4beta1 ; Leukapheresis ; Lymphocyte Function-Associated Antigen-1 ; Lymphoma, Non-Hodgkin ; Metalloproteases ; Multiple Myeloma ; Peptide Hydrolases ; Stem Cells ; Stromal Cells ; Tissue Donors ; Vascular Cell Adhesion Molecule-1

BACKGROUND/AIMS: Liver transplantation offers the only definite cure for cirrhosis but lacking donors is problem. Stem cell therapy is attractive in this setting. In this study, we aimed to explore the safety and efficacy of ultrasound-guided percutaneous portal transplantation of peripheral blood monocyte cell (PBMC) in cirrhotic patients. METHODS: A total of nine decompensated cirrhotic patients were randomized into three groups: group 1 (n = 3) was control group, group 2 (n = 3) received granulocyte-colony stimulating factor (G-CSF) mobilization for 3 days, and group 3 (n = 3) received G-CSF mobilized PBMCs by leukapheresis and PBMC transplantation through ultrasound-guided percutaneous portal vein puncture. Liver function and clinical features were evaluated. RESULTS: At baseline, the Child-Turcotte-Pugh and the model for end-stage liver disease scores were comparable in study groups. Compared with group 1, there was a tendency to improve liver function in group 3 at 6 months after treatment. Treatment was tolerable and no complications were encountered related to the G-CSF mobilization or percutaneous portal administration of PBMCs. Imaging studies showed patent portal veins at the end of the study period. CONCLUSIONS: Autologous PBMC transplantation through ultrasound-guided percutaneous portal vein puncture could be considered as a safe alternative treatment for decompensated cirrhotic patients.
Fibrosis ; Granulocyte Colony-Stimulating Factor ; Humans ; Leukapheresis ; Leukocytes, Mononuclear ; Liver Cirrhosis* ; Liver Diseases ; Liver Transplantation ; Liver* ; Monocytes* ; Portal Vein ; Punctures ; Stem Cells ; Tissue Donors

BACKGROUND: We compared the yields of mobilized PBSCs from single day of normal volume leukapheresis (NVL) in children and adults, and factors affecting the yields, to understand differences in mobilization efficiency between adults and small children with healthy marrows.METHODS: This study involved 18 adult volunteer donors and 47 small children weighing less than 20 kg who participated in a clinical trial of cell therapy in children with cerebral palsy. Donor factors analyzed to identify predictors of the yield of apheresis included age, gender, weight and complete blood cell count (CBC) with differential counts as well as equipment parameters.RESULTS: The yields of total nucleated cells (TNCs) and CD34⁺cells in the apheresis products of the children were significantly lower than in those from healthy adults. However, the efficiency of recovery of PBSCs (total CD34⁺ cell counts/TNCs) was significantly higher in small children (0.48±0.30%) than in adults (0.10±0.05%) (P < 0.05). Multivariable analysis of adult donor factors showed that the processed volume and flow rate of apheresis were significantly associated with the yield of TNCs (P < 0.05, for both), but not of CD34⁺cells. However, in multivariable analysis of child donor factors, body weight and circulating WBC count on the day of apheresis were significantly associated with the yield of TNCs (P < 0.05, for both) and of CD34⁺cells (P < 0.05, for both).CONCLUSION: The predictors of PBSC yields from a single day of NVL in adults and small children are different. Also mobilization is more effective in small children than in adults.
Adult ; Blood Cell Count ; Blood Component Removal ; Body Weight ; Bone Marrow ; Cell- and Tissue-Based Therapy ; Cerebral Palsy ; Child ; Hematopoietic Stem Cell Mobilization ; Humans ; Leukapheresis ; Tissue Donors ; Volunteers

BACKGROUND: Hyperleukocytosis is a medical emergency that is characterized by increased blood viscosity and predisposition to various neurological, pulmonary, and gastrointestinal complications. In addition, patients are at risk of the tumor lysis syndrome because of the increased tumor burden. Therapeutic leukapheresis is an important treatment for these emergent states. In this study, we retrospectively analyzed therapeutic leukapheresis procedures that were performed in our institution during the last 10 yr. METHODS: We retrospectively analyzed therapeutic leukapheresis procedures conducted from July 2005 to March 2015 at a tertiary care hospital. We present our observations, especially the procedural characteristics and hematological parameters before and after the aforementioned procedures. RESULTS: Seventy-two patients underwent a total of 146 therapeutic leukapheresis procedures. The average presenting white blood cell (WBC) count was 268×10(3)/µL, and ranged from 54×10(3)/µL to 673×10(3)/µL. After an average of two sessions, a statistically significant drop in the WBC counts was observed. The average WBC removal rates during the initial and entire therapeutic leukapheresis procedures of each patient were 33% and 46%, respectively. The platelet count and hemoglobin concentration were significantly reduced. CONCLUSIONS: Therapeutic leukapheresis significantly reduces peripheral WBC counts and is a safe and effective procedure for the treatment of hyperleukocytosis.
Blood Viscosity ; Emergencies ; Humans ; Leukapheresis* ; Leukemia ; Leukocytes ; Platelet Count ; Retrospective Studies ; Tertiary Healthcare* ; Tumor Burden ; Tumor Lysis Syndrome

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT) is the preferred curative therapy for children with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). We evaluated the treatment outcomes of children with Ph+ ALL who underwent allogeneic HSCT. METHODS: Fifteen children diagnosed with Ph+ ALL in Asan Medical Center Children's Hospital between 1998 and 2012 were retrospectively analyzed. RESULTS: Of 521 children diagnosed with ALL during the study period, 15 had a Philadelphia chromosome. Among these 15 patients, 13 attained complete remission (CR) following induction chemotherapy, and two died of intracerebral hemorrhage during leukapheresis and induction chemotherapy, respectively. Of the 13 patients who attained CR, 12 received allogeneic HSCT, mainly from unrelated donors. Of the 12 patients who received HSCT, one died of a transplant-related cause, one died of relapse after HSCT, and 10 remain in continuous CR. Of the 10 patients who remained in CR longer than six months after HSCT, seven received post-HSCT imatinib. For all 15 patients, the 5-year overall survival, event-free survival, and cumulative incidence of relapse were 60.0%, 48.6%, and 38.8%, respectively, with a median follow-up of 70 months. For the HSCT group, the 5-year overall survival, event-free survival, and cumulative incidence of relapse were 80.2%, 72.9%, and 29.3%, respectively, with a median follow-up of 100 months. CONCLUSION: Allogeneic HSCT cures a significant proportion of Ph+ ALL patients. Because the use of imatinib appears to be a promising approach, strategies that include tyrosine kinase inhibitors before and after HSCT require further evaluation.
Cerebral Hemorrhage ; Child* ; Chungcheongnam-do ; Disease-Free Survival ; Follow-Up Studies ; Hematopoietic Stem Cell Transplantation* ; Hematopoietic Stem Cells* ; Humans ; Incidence ; Induction Chemotherapy ; Leukapheresis ; Philadelphia Chromosome ; Precursor Cell Lymphoblastic Leukemia-Lymphoma* ; Protein-Tyrosine Kinases ; Recurrence ; Retrospective Studies ; Unrelated Donors ; Imatinib Mesylate