The efficacy of salvage interferon-α (IFN-α) treatment was investigated in patients with unsatisfactory response to minimal residual disease (MRD)-directed donor lymphocyte infusion (DLI) (n = 24). Patients who did not become MRD-negative at 1 month after DLI were those with unsatisfactory response and were eligible to receive salvage IFN-α treatment within 3 months of DLI. Recombinant human IFN-α-2b injections were subcutaneously administered 2-3 times a week for 6 months. Nine (37.5%), 6 (25.0%), and 3 (12.5%) patients became MRD-negative at 1, 2, and > 2 months after the salvage IFN-α treatment, respectively. Two-year cumulative incidences of relapse and non-relapse mortality were 35.9% and 8.3%, respectively. Two-year probabilities of event-free survival, disease-free survival, and overall survival were 51.6%, 54.3%, and 68.0%, respectively. Outcomes of patients subjected to salvage IFN-α treatment after DLI were significantly better than those with persistent MRD without IFN-α treatment. Moreover, clinical outcomes were comparable between the salvage DLI and IFN-α treatment groups. Thus, salvage IFN-α treatment may help improve the outcome of patients with unsatisfactory responses to MRD-directed DLI and could be a potential salvage treatment for these patients after allogeneic hematopoietic stem cell transplantation.
Adolescent ; Adult ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Beijing ; Child ; Child, Preschool ; Female ; Graft Survival ; Graft vs Host Disease ; mortality ; Hematopoietic Stem Cell Transplantation ; Humans ; Interferon-alpha ; therapeutic use ; Leukemia, Myeloid, Acute ; mortality ; therapy ; Lymphocyte Transfusion ; Male ; Middle Aged ; Myelodysplastic Syndromes ; mortality ; therapy ; Neoplasm, Residual ; Recurrence ; Salvage Therapy ; Survival Analysis ; Transplantation Conditioning ; Transplantation, Homologous ; Young Adult

Objective: To explore clinical features and severity of chronic graft- versus- host disease (cGVHD) after chemotherapy plus donor lymphocyte infusion (Chemo-DLI) in a consecutive cohort of acute leukemia patients who were minimal residual disease (MRD) positive after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: The global scoring system proposed by National Institutes of Health (NIH) Consensus Conference was used to identify the characteristics and severity of cGVHD in patients who MRD positive after Chemo-DLI. Results: 54 (59.3%) patients were diagnosed with cGVHD after Chemo-DLI, with the median time of onset of 70 (13-504) days. There were 6 cases (6.6%) of mild cGVHD, 21 cases (23.1%) of moderate cGVHD and 27 cases (29.7%) of severe cGVHD.The 5-year cumulative incidence of relapse after Chemo-DLI was 61.9% (95%CI 45.3%-78.5%) , 15.1% (95%CI 1.1%-29.1%) , and 26.6% (95%CI 9.2%-44.0%) (χ(2)=18.901, P<0.001) in non-cGVHD, mild to moderate cGVHD, and severe cGVHD groups, respectively. The 5-year cumulative incidence of relapse after Chemo-DLI was 61.9% (95%CI 45.3%-78.5%) , 19.9% (95%CI 8.1%-31.7%) , and 28.6% (95%CI 0.0%-65.0%) (χ(2)=18.307, P<0.001) in non-cGVHD, classical cGVHD, and overlap syndrome groups, respectively. cGVHD was not associated with non-relapse morality after Chemo-DLI. Probabilities of 5-year leukemia-free survival (LFS) after Chemo-DLI were 24.0% (95%CI 9.1%-38.9%) , 77.2% (95%CI 60.8%-93.6%) , and 64.9% (95%CI 45.7%-84.1%) (χ(2)=24.447, P<0.001) in non-cGVHD, mild to moderate cGVHD, and severe cGVHD groups, respectively. Probabilities of 5-year LFS after Chemo-DLI were 24.0% (95%CI 9.1%-38.9%) , 75.5% (95%CI 62.7%-88.3%) , and 42.9% (95%CI 1.8%-84.0%) (χ(2)=25.665, P<0.001) in non-cGVHD, classical cGVHD, and overlap syndrome groups, respectively. Probabilities of 5-year overall survival (OS) after Chemo-DLI were 50.0% (95%CI 31.1%-68.9%) , 87.9% (95%CI 74.7%-100.0%) , and 71.0% (95%CI 52.0%-90.0%) (χ(2)=9.517, P=0.009) in non-cGVHD, mild to moderate cGVHD, and severe cGVHD groups, respectively. Probabilities of 5-year OS after Chemo-DLI were 50.0% (95%CI 31.1%-68.9%) , 83.9% (95%CI 72.8%-95.0%) , and 51.4% (95%CI 6.2%-96.6%) (χ(2)=10.673, P=0.005) in non-cGVHD, classical cGVHD, and overlap syndrome groups, respectively. In multivariate analysis, patients receiving allo-HSCT in first complete remission stage and classical cGVHD after Chemo-DLI were associated with lower relapse risk and better survival. Conclusions: These findings highlight the close relation between cGVHD and the graft-versus-leukemia effect in patients who were MRD positive and received Chemo-DLI after allo-HSCT. However, overlap syndrome could not improve the clinical outcomes of these patients.
Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Humans ; Lymphocyte Transfusion ; Lymphocytes ; Neoplasm, Residual ; Prognosis ; Transplantation, Homologous

BACKGROUND: In Korea, there were repeated radiation exposure accidents among non-destructive testing workers. Most of the cases involved local injury, such as radiation burns or hematopoietic cancer. Herein, we report a case of acute radiation syndrome caused by short periods of high exposure to ionizing radiation. CASE PRESENTATION: In January 2017, Korea Information System on Occupational Exposure (KISOE) found that a 31-year-old man who had worked in a non-destructive testing company had been overexposed to radiation. The patient complained of symptoms of anorexia, general weakness, prostration, and mild dizziness for several days. He was anemic. The venous injection areas had bruises and bleeding tendency. Blood and bone marrow testing showed pancytopenia and the patient was diagnosed with acute radiation syndrome (white blood cells: 1400/cubic mm, hemoglobin: 7.1 g/dL, platelets: 14000/cubic mm). He was immediately prohibited from working and blood transfusion was commenced. The patient’s radiation exposure dose was over 1.4 Gy (95% confidence limits: 1.1–1.6) in lymphocyte depletion kinetics. It was revealed that the patient had been performing non-destructive tests without radiation shielding when working in high places of the large pipe surface. CONCLUSIONS: Exposure prevention is clearly possible in radiation-exposed workers. Strict legal amendments to safety procedures are essential to prevent repeated radiation exposure accidents.
Acute Radiation Syndrome ; Adult ; Anorexia ; Blood Cells ; Blood Transfusion ; Bone Marrow ; Burns ; Contusions ; Dizziness ; Hemorrhage ; Humans ; Information Systems ; Kinetics ; Korea ; Lymphocyte Depletion ; Occupational Exposure ; Pancytopenia ; Radiation Exposure ; Radiation, Ionizing

Asthma is a chronic disease of airway inflammation due to excessive T helper cell type 2 (Th2) response. Present treatment based on inhalation of synthetic glucocorticoids can only control Th2-driven chronic eosinophilic inflammation, but cannot change the immune tolerance of the body to external allergens. Regulatory T cells (Tregs) are the main negative regulatory cells of the immune response. Tregs play a great role in regulating allergic, autoimmune, graft-versus-host responses, and other immune responses. In this review, we will discuss the classification and biological characteristics, the established immunomodulatory mechanisms, and the characteristics of induced differentiation of Tregs. We will also discuss the progress of Tregs in the field of asthma. We believe that further studies on the regulatory mechanisms of Tregs will provide better treatments and control strategies for asthma.
Antigens, CD/analysis* ; Apyrase/analysis* ; Asthma/immunology* ; Cell Differentiation ; Cytokines/metabolism* ; Humans ; Lymphocyte Transfusion ; T-Lymphocytes, Regulatory/immunology*

Acute lymphocytic leukemia (ALL) is uncommon lymphoid malignancy in dogs, and its diagnosis is challenging. A 14-year-old spayed female mixed breed dog was transferred to a veterinary medical teaching hospital for an immediate blood transfusion. The dog showed lethargy, pale mucous membranes, and a weak femoral pulse. Complete blood count revealed non-regenerative anemia and severe leukopenia with thrombocytopenia. ALL was tentatively diagnosed based on the predominance of immature lymphoblasts on blood film examination. For confirmation of lymphoid malignancy, PCR for antigen receptor rearrangement (PARR) on a peripheral blood sample and flow cytometry analysis were performed after blood transfusion. Flow cytometry analysis revealed that lymphocyte subsets were of normal composition, but PARR detected a T-cell malignancy. The dog was diagnosed with ALL and survived 1 wk after diagnosis. In conclusion, after blood transfusion, flow cytometry was not a reliable diagnostic method for an ALL dog, whereas PARR could detect lymphoid malignancy. Our results suggest that PARR should be the first-line diagnostic tool to detect canine lymphoid malignancy after a blood transfusion.
Adolescent ; Anemia ; Animals ; Blood Cell Count ; Blood Transfusion* ; Diagnosis* ; Dogs* ; Female ; Flow Cytometry ; Hospitals, Teaching ; Humans ; Lethargy ; Leukopenia ; Lymphocyte Subsets ; Methods ; Mucous Membrane ; Polymerase Chain Reaction* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma* ; Receptors, Antigen* ; T-Lymphocytes ; Thrombocytopenia

PURPOSE: The aim of this study was to evaluate the impact of perioperative nutrition and transfusion affecting postoperative complications in gastric surgery.METHODS: From January through December in 2013, 181 patients who underwent curative gastrectomy for gastric adenocarcinoma at Korea University Guro Hospital were included. We collected general information, nutritional parameters (serum hemoglobin, albumin, total lymphocyte counts, and body mass index), operative method, perioperative transfusion and postoperative complications. The patients were divided into two groups by Clavien-Dindo classification: group I, no complication and Grade I complication; group II, above Grade II complication.RESULTS: The mean age of patients was 62.06 years, and 119 (65.7%) patients were men. The number of patients who suffered complications was 81 (44.8%), group I was 38 (21.0%) and group II was 33 (18.2%). According to the results of univariate analysis, sex, age, comorbidities, the American Society Anesthesiologists (ASA) classification and operative method had no significant effect on postoperative complications. Also in nutritional factors, serum hemoglobin, albumin, total lymphocyte counts, body mass index had no significant correlation with postoperative complications. The only independent factor correlated with postoperative complications was perioperative transfusion (odds ratio [OR], 2.424, 95% confidence interval [CI], 1.064–5.525; P=0.035) and operation time (OR, 1.007; 95% CI, 1.001–1.013; P=0.027) according to univariate analysis as well as multivariate analysis.CONCLUSION: This study suggests that perioperative transfusion may play a significant role in the development of postoperative complications.
Adenocarcinoma ; Blood Transfusion ; Body Mass Index ; Classification ; Comorbidity ; Gastrectomy ; Humans ; Korea ; Lymphocyte Count ; Male ; Methods ; Multivariate Analysis ; Nutritional Status ; Postoperative Complications ; Stomach Neoplasms

OBJECTIVETo investigate the efficacy of donor lymphocyte infusion (DLI) for treating relapsed high-risk leukemia patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT).

METHODSThe data of 15 leukemia patients who had received DLI and 13 leukemia patients who had not received DLI in Zhujiang Hospital from 2000 to 2014 were studied retrospectively, and their 1 and 3 year overall survival rate (OS) were compared between the two groups.

RESULTSIn 15 patients received DLI, the 1 and 3 year OS were 58.3% and 46.7%, the 1 and 3 year disease-free survival (DFS) were 22.0% and 11.0%, respectively. The main death cause in these patients included relapse (n = 5) and acute GVHD (n = 1), whereas in 13 patients who had not received DLI, the 1 and 3 year OS were 29.9% and 15.0% respectively, their 1 year DFS were 11.2%. The main death cause in these patients were relapse (n = 9). The 1 and 3 year OS of patients who had received DLI was higher as compared with the patients who had not received DLI. but this difference was no statistically significant (P = 0.069).

CONCLUSIONDLI is an effective method for treating patients with relapsed leukemia, and may improve the therapeutic efficacy of DLI by combining other methods or alternating the types of the donor lymphocytes.

Disease-Free Survival ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia ; Lymphocyte Transfusion ; Lymphocytes ; Recurrence ; Retrospective Studies ; Survival Rate ; Transplantation, Homologous

Adolescent ; Antibodies, Monoclonal ; therapeutic use ; Antigens, Neoplasm ; immunology ; Cancer Vaccines ; immunology ; Child ; Child, Preschool ; Humans ; Immunotherapy ; methods ; Infant ; Killer Cells, Natural ; immunology ; Lymphocyte Transfusion ; Neoplasms ; immunology ; therapy ; Pediatrics ; Stem Cell Transplantation

OBJECTIVETo study the effect of pretreatment with apoptotic donor spleen cells on spleen lymphocyte function of recipient rats undergoing islet transplantation to explore new approaches to prolong islet graft survival.

METHODSApoptotic spleen cells from donor rats were obtained by exposure to γ-ray irradiation from (60)Co. Diabetic SD rat models were randomly divided into 4 groups to receive tail vein injections with saline (group A), normal cells (group B), apoptotic donor cells (group C), or necrotic donor cells (group D). One week later, orthotopic transplantation of islets under the renal capsule was performed. Before and at 1 and 2 weeks after islet transplantation, the recipient rats were examined for proliferative activity of spleen lymphocytes with CFSE cell staining and for IL-2 and IL-10 expressions in the cells using ELISA.

RESULTSPretreatment with donor apoptotic cells significantly suppressed the proliferative activity of recipient spleen lymphocytes before and at 1 and 2 weeks after islet transplantation as compared with the other three groups (P<0.05). The level of IL-2 was significantly decreased while IL-10 increased in apoptotic donor cell pretreatment group compared with those in the other 3 groups at each time point of observation.

CONCLUSIONThe effect of pretreatment with apoptotic donor cells on recipient spleen lymphocytes suggest an important role of apoptotic donor spleen cells in immune tolerance of grafts.

Animals ; Apoptosis ; immunology ; Cell Proliferation ; Cobalt Radioisotopes ; Diabetes Mellitus, Experimental ; metabolism ; pathology ; surgery ; Gamma Rays ; Graft Survival ; Immune Tolerance ; Interleukin-10 ; metabolism ; Interleukin-2 ; metabolism ; Islets of Langerhans Transplantation ; Lymphocyte Transfusion ; Lymphocytes ; metabolism ; pathology ; radiation effects ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar ; Spleen ; cytology ; metabolism ; radiation effects

OBJECTIVETo evaluate the anti-leukemia effects of prophylactic G-CSF mobilized donor lymphocytes infusion (pG-DLI) and its relationship with the incidence of graft-versus-host disease (GVHD) in high-risk leukemia patients with non-myeloablative stem cell transplantation (NST).

METHODS12 patients with high-risk leukemia were analyzed, including Ph⁺ acute lymphocytic leukemia (n=1), acute leukemia (AL) with persistent non-complete remission (n=2), acute myeloid leukemia (AML) with central nervous system (CNS) relapse (n=3), hybrid AL (n=1), secondary AML evolving from myelodysplastic syndrome (MDS/AML) (n=2), chronic myeloid leukemia in accelerated phase (CML-AP) (n=1), CML in blastic phase (CML-BP) (n=2). All patients received non-myeloablative conditioning and pG-DLIs were administered 30-40 days post transplantation if no signs of GVHD were present. The percentage of donor cell chimera was analyzed by short tandem repeat-polymerase chain reaction (STR-PCR) just before and after pG-DLI. The incidence of leukemia relapse and GVHD were observed.

RESULTS12 high-risk leukemia patients with a median age of 38 (range: 29-52) years received G-DLI at a median interval of 35 (32-40) days. The median numbers of infused mononuclear cells (MNCs), CD34⁺, and CD3⁺ cells/kg recipient body weight was 2.3×10⁸/kg, 1.7×10⁶/kg, and 0.6×10⁸/kg, respectively. 10 of 12 patients had full donor chimera before pG-DLIs and conversion from mixed to full donor chimera occurred in the other 2 patients shortly after pG-DLI. Grade II acute GVHD (aGVHD) was observed in only 2 patients and chronic GVHD (cGVHD) developed in 6 patients, including involvement of skin (n=3), skin and intestine (n=2), liver (n=1). 1 patient died of cGVHD. With a median follow-up of 40 (24-64) months, 7 patients are alive in remission, with 3-year actuarial overall survival (OS) and disease-free survival (DFS) rates of the same 58.3%.

CONCLUSIONOur findings indicate that pG-DLI after NST does not increase the risk of aGVHD, but could enhance the capacity graft-vs-leukemia and prevent relapse in high-risk leukemia patients.

Adult ; Female ; Graft vs Host Disease ; prevention & control ; Granulocyte Colony-Stimulating Factor ; Hematopoietic Stem Cell Transplantation ; adverse effects ; methods ; Humans ; Leukemia ; surgery ; Lymphocyte Transfusion ; methods ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; prevention & control ; Tissue Donors ; Transplantation, Homologous