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

OBJECTIVETo explore the kinetics of platelet reconstitution and its prognostic significance in patients received unmanipulated haploidentical stem cell transplantation (Haplo-HSCT) without in vitro T cell depletion.

METHODSA total of 291 patients received Haplo-HSCT without in vitro T cell depletion between January 2007 to December 2008 were retrospectively reviewed. They were categorized into 3 groups according to the platelet count on day 30, day 60 and day 90: (1) persistent thrombocytopenia (Group A) was defined as the platelet count never reached 50×10⁹/L on the three time points; (2) unstable thrombocytopenia (Group B): the platelet count recovered to a level of 50×10⁹/L by day 30 or 60 or 90, yet did not reach a level of more than 100×10⁹/L; (3) non-thrombocytopenia (Group C): the platelet count was higher than 100×10⁹/L on day 90. The kinetics of platelet reconstitution, overall survival (OS) and treatment related mortality (TRM) were compared between 3 groups.

RESULTSOf the 291 consecutive patients, 288 cases engrafted successfully and 262 cases were platelet transfusion independent. The median intervals of neutrophil and platelet engraftment were 13 (9-29) days and 17 (7-180) days, respectively. The cumulative incidence of grade III-IV acute graft versus host disease (GVHD) on day 100 and chronic GVHD at 3 years were 14.7% and 56.4% respectively. OS and TRM at 3 years were 64.6% and 22.3% respectively. At the end of the follow-up, 266 cases were platelet transfusion independent: including 71 (24.4%) cases in Group A, 147 (50.5%) in Group B and 73 (25.1%) in Group C. OS in group A, B and C was 38.0%, 69.4% and 80.8% (P<0.05) respectively. TRM in Group A, B and C was 53.5%, 17.7% and 1.4% (P<0.05) respectively. Persistent thrombocytopenia was related with lower OS and higher TRM in multivariate analysis.

CONCLUSIONPersistent thrombocytopenia was common after Haplo-HSCT without in vitro T cell depletion, and patients with persistent thrombocytopenia have poor OS and higher TRM.

Adolescent ; Adult ; Blood Platelets ; Child ; Child, Preschool ; Female ; Hematopoietic Stem Cell Transplantation ; adverse effects ; methods ; Humans ; Lymphocyte Depletion ; adverse effects ; Male ; Middle Aged ; Platelet Count ; Prognosis ; Retrospective Studies ; Thrombocytopenia ; etiology ; Treatment Outcome ; Young Adult

Recent advances in the understanding of the biology of Hodgkin lymphoma have led to a new classification. Hodgkin lymphoma is now recognized as a B-cell disorder of germinal center or post-germinal center origin. In the WHO classification, Hodgkin lymphoma consists of two categories, namely, nodular lymphocyte predominant Hodgkin lymphoma and classical Hodgkin lymphoma. Classical Hodgkin lymphoma encompasses not only nodular sclerosis, mixed cellularity, and lymphocyte depletion subtypes, but also lymphocyte-rich subtype, among which, nodular sclerosis stands out as a distinct entity. A borderline neoplasm with features intermediate between Hodgkin lymphoma and diffuse large B-cell lymphoma has also been recognized.
B-Lymphocytes ; Biology ; Diagnosis, Differential ; Germinal Center ; Hodgkin Disease ; Lymphocyte Depletion ; Lymphocytes ; Lymphoma, B-Cell ; Sclerosis

Depletion of T and B cells from the graft is prerequisite for haploidentical transplantation to decrease the risk of GVHD and EBV-associated lymphoproliferative disease. This study was aimed to investigate the performance of T-cell and B-cell simultaneous depletion from mobilized peripheral blood stem cells (PBSCs) for the first time in China, using anti-CD3 and anti-CD19 antibodies conjugated to magnetic microbeads by the CliniMACS device. The depletion efficiency of T-cell and B-cells was analyzed by flow cytometry; the function of the stem cells after depletion was evaluated using colony assays. The results indicated that the mononuclear cell count prior to T- and B-cell depletion was 4.88 x 10(10). After depletion, the percentage of T cells was 0.02% with a log (10) depletion of 4.4. The percentage of B cells was less than 0.01% with a log (10) depletion of at least 3.3. The product contained not only CD34(+) stem cells, but also NK cells, monocytes and granulocytes. After T- and B-cell depletion the purity of CD34(+) cells was 0.98%, the number of CD34 cells was 1.84 x 10(8) and their recovery rate was 69.7%. The number of NK cells was 2.54 x 10(9) and the recovery rate of NK cells was 71.7%. In vitro colony assays showed no negative impact on function of the hematopoietic stem cells. In conclusion, the CliniMACS system can be used to efficiently deplete T and B cells from PBSCs simultaneously, without adverse effect on biological function of hematopoietic stem cells. This study provides technical platform for haploidentical hematopoietic stem cell transplantation.
Antigens, CD34 ; immunology ; B-Lymphocytes ; immunology ; CD3 Complex ; immunology ; Hematopoietic Stem Cell Transplantation ; methods ; Humans ; Lymphocyte Depletion ; methods ; Peripheral Blood Stem Cell Transplantation ; methods ; T-Lymphocytes ; immunology

This study was aimed to investigate a new method of avoiding graft-vs-host disease (GVHD) through selective elimination of alloreactive donor lymphocytes by using total body irradiation (TBI) and cyclophosphamide (Cy). Female (BALB/c x C57BL/6) F1 mice (H-2(d/b)) as recipients received (60)Co gamma-ray sublethal TBI of 4 Gy on day 0 followed by being inoculated with P388D1 leukemia cell line on day 1, injection of allogeneic splenocytes from C57BL/6 male mice (H-2(b)) was carried out for induction of graft-vs-leukemia (GVL) effect prior to stem cell transplantation (SCT), intraperitoneally injection of cyclophosphamide (Cy) (200 mg/kg) and TBI (9 Gy) was given on day 6. One day later, treated mice were rescued with bone marrow hematopoietic stem cells from (BALB/c x C57BL/6) F1 male mice (H-2(d/b)). The results showed that recipients had no occurrence of leukemia and GVHD through selective elimination of alloreactive donor lymphocytes by Cy and TBI, survived more than 210 days, the complete-donor chimerism occurred on day 21 after transplantation. The ratio of chimerism descended subsequently, but still displayed mixed-chimerism at 90 days. Control mice died of GVHD, leukemia or other death-related-transplantation within 20 to 36 days (P<0.01). It is concluded that to induce GVL effects by MHC mismatched splenocytes given before syngeneic bone marrow transplantation followed by selective elimination of alloreactive donor lymphocytes through TBI and Cy, graft-vs-host disease was thus avoided.
Animals ; Cyclophosphamide ; therapeutic use ; Female ; Graft vs Host Disease ; prevention & control ; Graft vs Tumor Effect ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Leukemia P388 ; therapy ; Lymphocyte Depletion ; Lymphocytes ; immunology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Whole-Body Irradiation

Blockade of signal 1 or 2 for T-cell activation by the use of anti-CD45RB and anti-CD154 monoclonal antibodies (mAb) (two-signal blockade) has been proven effective in preventing or delaying graft rejection. However, the mechanisms of its immunomodulatory effects are clearly unknown and the present studies were performed to determine how the two-signal blockade modulate allogeneic immune responses, especially T-cell mediated cellular immunity, in a murine skin allograft model. We now report on the profound inhibition of alloreactive T cells by two-signal blockade via CD4-dependent mechanisms. C57BL/6 mice of BALB/c skin allograft were treated with anti-CD45RB, anti-CD154, CTLA4-Ig, or their combinations. For depletion of CD4 or CD8 T cells, the recipients received CD4-depleting or CD8-depleting mAb. We confirmed that survival of skin allograft was markedly prolongated in the two-signal blockade-treated group. In depletion study, anti-CD45RB, anti-CD154 and CD4-depleting mAb-treated group showed acute rejection of skin allograft in contrast to CD8-depleting group treated with the two-signal blockade. In the group treated with the two-signal blockade, the proportions of CD4+CD45RB(low)and CD8+CTLA-4 regulatory T cells were increased while effector CD8+ T cells, including IFN-gamma-secreting and CD8+CD62L(low)T cells, were decreased when compared with non-treated group. In contrast, the CD4-depleted group treated with the two-signal blockade resulted in recovery from immunoregulatory effects of two-signal blockade. In addition, results of IL-4 and IL-10 production were also showed CD4-dependence. Therefore, the two-signal blockade is accompanied by CD4-dependent mechanisms in allogeneic skin transplantation.
Transplantation, Homologous ; T-Lymphocytes, Regulatory/cytology/immunology ; Skin Transplantation/*immunology ; Signal Transduction/drug effects/immunology ; Mice, Inbred C57BL ; Mice, Inbred BALB C ; Mice ; Male ; Lymphocyte Depletion ; Lymphocyte Activation/immunology ; Interleukin-4/biosynthesis ; Interleukin-10/biosynthesis ; Graft Rejection/*immunology/prevention & control ; Flow Cytometry ; Cytotoxicity, Immunologic/immunology ; CD8-Positive T-Lymphocytes/cytology/immunology/metabolism ; CD40 Ligand/*immunology ; CD4-Positive T-Lymphocytes/cytology/immunology/metabolism ; Antigens, CD45/*immunology ; Antigens, CD4/*immunology ; Antibodies, Monoclonal/administration & dosage/*pharmacology ; Antibodies, Blocking/administration & dosage/pharmacology ; Animals

OBJECTIVETo study the effect of alloreactive natural killer (NK) cells used in conditioning regimen on elimination of recipient-type T cell and granulocyte, reconstitution of hematopoiesis, engraftment and graft-versus-host disease (GVHD) in murine major histocompatibility complex (MHC) haploidentical bone marrow transplantation (BMT).

METHODSThe murine model of MHC haploidentical BMT was established by using (C57BL/6 x BALB/c) BCF(1) (H-2(d/b)) mouse as the donor, and BALB/c (H-2(d)) mouse as the recipient. Recipient mice were divided into 8.5 Gy control group and 7, 6 and 5 Gy experimental groups according to different irradiation dose and different kinds of NK cell treatment. The control group was further subdivided into untreated and BMT groups, while each experimental group was subdivided respectively into untreated group, BMT group, non-allo-reactive NK cells (non-allo NK) group and alloreactive NK cells (allo NK) group. The effect of adding alloreactive NK cell to conditioning regimen was assessed by peripheral white blood cell and platelet counts, recipient type H-2(d+) T cells and granulocytes counts, expression of H-2(d/b+) cells and pathohistological examination.

RESULTSSurvival time was (6.00 +/- 0.82) days for 8.5 Gy untreated group, and beyond 60 days for all the other groups. No clinical and histopathological evidence of GVHD was observed in all the groups. The reconstitution of hematopoiesis was faster in allo NK groups than in other groups (P < 0.05). On day 1 after BMT, in allo NK groups with different irradiation dose, bone marrow and spleen recipient type H-2(d+) granulocytes and T cells were significantly decreased compared with identical BMT groups and non-allo NK groups (P < 0.05). The engraftment rates of H-2(d/b+) cells were significantly higher in 7, 6 and 5 Gy allo NK groups than in identical BMT groups and non-allo NK groups (P < 0.05, respectively).

CONCLUSIONSIn mouse MHC haploidentical BMT, alloreactive NK cell can eliminate recipient-type T cell and granulocyte, promote reconstitution of hematopoiesis, enhance engraftment while not induce GVHD.

Animals ; Bone Marrow Transplantation ; immunology ; methods ; Graft vs Host Disease ; immunology ; prevention & control ; Killer Cells, Natural ; immunology ; Lymphocyte Depletion ; Major Histocompatibility Complex ; immunology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Transplantation Conditioning ; methods ; Transplantation, Homologous ; immunology ; methods

OBJECTIVE: To determine preliminary evidence for the safety and efficacy of B lymphocyte depletion therapy in refractory systemic lupus erythematosus (SLE). METHODS: Four female lupus nephritis patients who had been refractory to steroid and one or more immunosuppressive therapy were treated on an open-label basis. During a 4-week period, each patient received two 500-mg infusions of rituximab and two 750-mg infusions of cyclophosphamide. RESULTS: Patient 1, 2, and 3 were responded with rituximab treatment with improvements in SLEDAI and laboratory parameters such as C3/C4 and 24 hour urine protein. However, patient 4 had not improved with rituximab. The variation in the level of anti-double-stranded DNA antibody was different in individual patients. No significant adverse events were observed during follow-up. CONCLUSION: This study provides an evidence for the safety and possible efficacy of B lymphocyte depletion therapy in refractory lupus nephritis. However a further randomized trial is needed to confirm the efficacy and durability of remission.
Cyclophosphamide ; DNA ; Female ; Follow-Up Studies ; Humans ; Lupus Erythematosus, Systemic ; Lupus Nephritis* ; Lymphocyte Depletion ; Rituximab

Immunization with dendritic cells (DCs) pulsed with tumor antigen can activate tumor-specific cytotoxic T lymphocytes (CTL), which is responsible for tumor protection and regression. In this study, we examined whether DCs pulsed with necrotic tumor lysates can efficiently prevent malignant melanoma tumor cell metastasis to the lung. DCs derived from mouse bone marrow were found to produce remarkably elevated levels of IL-12 after being pulsed with the tumor lysates. Moreover, immunization with these DCs induced CTL activation and protected mice from metastasis development by intravenously inoculated tumor cells. In addition, these DCs activated NK cells in vitro in a contact-dependent manner, and induced NK activities in vivo. Furthermore, NK cell depletion before DC vaccination significantly reduced the tumor-specific CTL activity, IFN-g production, and IFN-gamma- inducible gene expression, and eventually interfered with the antitumor effect of tumor-pulsed DCs. Finally, similar findings with respect to NK cell dependency were obtained in the C57BL/ 6J-bg/bg mice, which have severe deficiency in cytolytic activity of NK cells. These data suggest that the antitumor effect elicited by DC vaccination, at least in a B16 melanoma model, requires the participation of both cytolytic NK and CD8+ T cells. The findings of this study would provide important data for the effective design of DC vaccines for cancer immunotherapy.
Animals ; Antigen Presentation/immunology ; CD8-Positive T-Lymphocytes/immunology ; Cancer Vaccines/*therapeutic use ; Cell Line, Tumor ; Cytokines/biosynthesis/immunology ; Dendritic Cells/immunology/*transplantation ; Female ; Interferon Type II/biosynthesis/immunology ; Interleukin-12/biosynthesis/immunology ; Killer Cells, Natural/*immunology ; Lung Neoplasms/immunology/prevention & control/secondary ; Lymphocyte Activation/immunology ; Lymphocyte Depletion ; Melanoma, Experimental/immunology/secondary/*therapy ; Mice ; Mice, Inbred C57BL ; Monocyte Chemoattractant Proteins/biosynthesis/immunology ; Research Support, Non-U.S. Gov't ; T-Lymphocytes, Cytotoxic/immunology

This study was aimed to investigate the clinical outcome of ricin-immunotoxin mediated T cell partially depleted HLA/MLC mismatched allogeneic hematopoietic stem cell transplantation. 13 patients with hematological malignancies were treated by ricin-immunotoxin mediated T cell partially depleted allogeneic hematopoietic stem cell transplantations from HLA/MLC mismatched donors, including 6 cases of CML in CP(1), 1 case of ALL in CR(1), 1 case of ALL in CR(2), 1 case of ALL in relapse, 2 cases of AML in CR(1), 1 case of AML in CR(2), 1 case of MDS-RAEBT-AML (M(4)) in CR(1). The results showed that 8 cases were engrafted successfully, 2 cases of them developed grade II acute GVHD and 2 cases developed grade III-IV acute GVHD. Within following-up of 8 - 90 months, 2 patients who experienced grade III-IV acute GVHD died early after transplantation; 1 patient died of late onset of infection; the other 5 patients survived free from diseases. After failure at first infusion, 4 patients were given reinfusion of peripheral blood hematopoietic stem cells from the same donor. 3 out of 4 cases failed to engraft and only one patient got engraftment but died of related complications of transplantation. One patient was performed a second transplantation from a syngeneic donor and survive free of disease until now. In conclusion, T cell partially depleted HLA/MLC mismatched allogeneic hematopoietic stem cell transplantation by ricin-immunotoxin decreases the occurrence of severe acute GVHD but with high risk of rejection, which clinical outcome still needs further evaluation.
Adolescent ; Adult ; Child ; Female ; Graft vs Host Disease ; epidemiology ; Hematopoiesis ; Hematopoietic Stem Cell Transplantation ; mortality ; Humans ; Immunotoxins ; pharmacology ; Lymphocyte Depletion ; methods ; Male ; Ricin ; pharmacology ; T-Lymphocytes ; drug effects ; Transplantation, Homologous