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

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

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*

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

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

This study was purposed to investigate the therapeutic effects of early transfusion of immunized donor lymphocytes after haploidentical transplantation by means of mouse model of nonmyeloablative haploidentical bone marrow transplantation. CB6F1 female mouse was served as recipient and C57BL/6 male mouse was served as donor. Each CB6F1 female mouse was subjected to intravenous transfusion with 1×10(6) erythroleukemia (EL9611) cells at day 4 before transplantation, followed with intraperitoneal injection of Ara-C (0.015 g) respectively at day 2 and day 1, then conditioned for BMT with TBI (450 cGy) at day 1 before transplantation. After conditioning (day 0), each of recipients was transplanted with 6×10(7) mixture of bone marrow and spleen cells from the C57BL/6 mice, and was infused with 6 × 10(7) immunized donor lymphocytes at day 15 after transplantation. All treated animals were evaluated for survival, development of leukemia and aGVHD. The donor CD3(+) cell chimerism and sex determining region Y gene (SRY)in recipients were monitored periodically after transplantation. The results showed tht all mice with only inoculation of 10(6) EL9611 cells survived for 15 ± 1 days (n = 4); all mice of other groups obtained the varying degrees of implantation. SRY could be detected at day 30 and 60 after transplantation. The chimerism of donor CD3(+) cells in mixed bone marrow transplantation (MT) group at day 14, 30 and 60 respectively reached 17.95% ± 12.03%, 37.34% ± 2.78% and 47.06% ± 6.1%. In donor lymphocyte infusion (DLI) group it reached 69.78% ± 12.62%, 75% ± 15.97%, 83.41% ± 16.07% at day 30, 45 and 60 after transplantation. The mice of MT and DLI group survived for 66.66 ± 1.47 days and 78.2 ± 7.82 days. It is concluded that the high tumor burden before transplantation can affect donor cell engraftment and prognosis.Early post-transplanted infusion of immunized lymphocytes from donor can help to improve the therapeutic efficacy and survival.
Animals ; Bone Marrow Transplantation ; methods ; Female ; Haplotypes ; Leukemia, Erythroblastic, Acute ; therapy ; Lymphocyte Transfusion ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Tissue Donors ; Transplantation Conditioning ; methods ; Transplantation, Homologous

This study was aimed to observe the clinical efficacy and adverse effects of decitabine plus improved CAG chemotherapy and haploid-identical donor peripheral lymphocyte infusion regimen on elderly patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Five elderly patients with MDS and AML were treated with decitabine plus improved CAG chemotherapy and donor peripheral lymphocyte infusion regimen. Examinations on liver and renal function, electrocardiogram and bone marrow analysis were performed before and after treatment, and adverse effects were observed. The results indicated that after a course of treatment by decitabine plus improved CAG chemotherapy and haplo-identical donor peripheral lymphocyte infusion regimen, the total effective rate was 100%, and 4 patients (80%) achieved complete remission, 1 patient achieved partial remission. The dominant clinical adverse effect was bone marrow depression, the median time of neutrophil>0.5×10(9)/L and platelet>20×10(9)/L was 15 d and 16 d respectively for patients without previous MDS. It is concluded that decitabine plus improved CAG chemotherapy and haploid-identical donor peripheral lymphocyte infusion regimen may be effective with less adverse effects for elderly primary AML and high risk MDS patients, it is a promising therapeutic methods and worthy to deeply study.
Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Azacitidine ; administration & dosage ; analogs & derivatives ; therapeutic use ; Female ; Haploidy ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; therapy ; Lymphocyte Transfusion ; Lymphocytes ; Male ; Middle Aged ; Myelodysplastic Syndromes ; drug therapy ; therapy ; Treatment Outcome