A thymic carcinoma is a rare malignant neoplasm of the thymus epithelium, which can be distinguished from a benign or invasive thymoma. Contrary to a thymoma, the association of a thymic carcinoma and autoimmune disease is rare, with only a few cases having been reported. Herein, a case of thymic carcinoma diagnosed concurrently with systemic lupus erythematosus (SLE) is reported. A 49 year-old man presented at our clinic with myalgia. He was diagnosed with SLE, based on an oral ulcer, lymphopenia, and positive ANA and anti-Sm antibodies. Incidentally, a routine chest X-ray showed a large mediastinal mass. Pathological examination of the mediastinal mass revealed an undifferentiated thymic carcinoma, of WHO classification type C. Further work-up for staging showed multiple bone and lung metastases. With a palliative aim, he received systemic chemotherapy, but refused further chemotherapy after the 2nd course. Currently, the patient has not been followed up since the chemotherapy.
Antibodies ; Autoimmune Diseases ; Classification ; Drug Therapy ; Epithelium ; Humans ; Lung ; Lupus Erythematosus, Systemic* ; Lymphopenia ; Middle Aged ; Myalgia ; Neoplasm Metastasis ; Oral Ulcer ; Thorax ; Thymoma* ; Thymus Gland

OBJECTIVETo explore mechanisms of the augmented anti-tumor immunity observed in reconstituted lymphopenic mice (RLM) receiving melanoma vaccination.

METHODSThe study is to investigate the anti-tumor immunity of tumor vaccination during early immune reconstitution period following irradiation and cyclophosphamide (CY)-induced lymphopenia. Lymphopenic mice were subsequently reconstituted with naive splenocytes from syngeneic mice and immunized with irradiated melanoma cells F10 (irradiation experiment) and GM-CSF-modified D5 melanoma cells (D5-G6) (CY experiment). Controls included normal C57BL/6 mice receiving the corresponding vaccination, un-immunized naive mice and RLM. 8 - 10 days after vaccination, tumor vaccine draining lymph nodes (TVDLN) were harvested and phenotyped by FACS analysis. T cells purified from TVDLN were stimulated with anti-CD3 and anti-TCRbeta and proliferation was assessed by [(3)H]-TdR incorporation and FACS assay was performed for CD69 expression.

RESULTSThe augmented anti-tumor immunity correlated with a significant increase in the percentage of T cells with activation/memory phenotype in the TVDLN of vaccinated RLM, compared to that of the controls. There was also a significant increase in the density of DCs in TVDLNs. The activation threshold of T cells generated from vaccinated RLM was significantly decreased, resulting in markedly enhanced proliferating capability upon anti-CD3 stimulation.

CONCLUSIONThis study suggests that the augmented anti-tumor immunity observed in vaccinated RLM is due to down regulated activation threshold of T cells during lymphopenia-driven T cell proliferation, which may in turn facilitate the breaking down of immune tolerance to weak tumor antigens upon vaccination with tumor cell vaccines.

Animals ; Cancer Vaccines ; administration & dosage ; Cyclophosphamide ; Lymph Nodes ; immunology ; Lymphopenia ; etiology ; immunology ; Male ; Melanoma, Experimental ; immunology ; therapy ; Mice ; Mice, Inbred C57BL ; T-Lymphocytes ; immunology ; Whole-Body Irradiation

BACKGROUND: The aim of this study is to investigate the hematological manifestations of human immunodeficiency virus (HIV) infection, the risk factors for cytopenia, and the effect of highly active anti-retroviral therapy (HAART) on cytopenia. METHODS: Medical records of patients treated for HIV at the Seoul National University Hospital from January 2005 to March 2010 were retrospectively reviewed. To determine the impact of HIV itself, we excluded HIV patients who had other conditions that could have resulted in hematological manifestations. Multiple logistic regression analyses were performed to identify risk factors for cytopenia. RESULTS: A total of 621 cases were investigated, and after exclusion, data of 472 patients were analyzed. The frequency of cytopenia was anemia, 3.0% (14/472); neutropenia, 10.0% (47/472); thrombocytopenia, 2.4% (12/472); lymphopenia, 25.7% (121/470); isolated cytopenia, 11.2% (53/472); and bicytopenia, 2.1% (10/472). The leading risk factor for cytopenia identified by multivariate logistic regression methods was AIDS status at initial presentation. After HAART, cytopenia was reversed in the majority of patients (thrombocytopenia, 100%; neutropenia, 91.1%; and anemia, 84.6%). CONCLUSION: This study isolated the impact of HIV infection alone on hematologic manifestations and confirmed that these changes were reversible by HAART. Control of the HIV infection will have the main role in the management of hematological manifestations of the virus.
Anemia ; Antiretroviral Therapy, Highly Active ; HIV ; HIV Infections ; Humans ; Logistic Models ; Lymphopenia ; Medical Records ; Neutropenia ; Retrospective Studies ; Risk Factors ; Thrombocytopenia ; Viruses

OBJECTIVETo test whether vaccination performed during irradiation or chemotherapeutics-induced lymphopenia-driven T cell proliferation could augment the antitumor immunity.

METHODSThe study composed of two parts, investigating the anti-tumor efficacy of performing tumor vaccination during early immune reconstitution period following sublethal total body irradiation and cyclophosphamide (Cy)-induced lymphopenia, respectively. Mice were subsequently reconstituted with naïve splenocytes from syngeneic mice and were named RLM (Reconstituted lymphopenic mice). Immunization/vaccination (F10) and adoptive immunotherapy (D5-G6) were used to explore anti-tumor immune responses in vaccinated irradiation/RLM and vaccinated Cy/RLM, respectively. Both normal C57BL/6 mice and RLM were vaccinated with irradiated, weakly immunogenic F10 melanoma cells and subsequently challenged with F10 cells. In addition, to determine the role of CD4(+) and CD8(+) T cells in the protective anti-tumor immune response, irradiation/RLM were depleted of these subpopulations by administration of the appropriate mAb around challenge. In the second part, adoptive immunotherapy was used to evaluate the anti-tumor immune responses under chemotherapeutics-induced lymphopenic condition. Both normal mice and RLM (Cy-treated) were vaccinated with GM-CSF-modified D5 melanoma cells (D5-G6) and tumor vaccine draining lymph nodes (TVDLN) were harvested 9-10 days later. Effector T cells were generated in vitro from TVDLN cells and adoptively transferred to mice bearing 3-day pre-established pulmonary metastases (D5). Recipient mice were sacrificed 2 weeks later after tumor inoculation and pulmonary metastases were enumerated.

RESULTSSignificantly greater protection was induced in vaccinated irradiation/RLM, compared to vaccinated normal mice (63.2% vs 16.7%). Protective immunity in RLM depended on CD8(+) T cells. Increase in the interval between reconstitution and vaccination significantly decrease the protection. Effector T cells generated from vaccinated Cy-treated RLM demonstrated significantly higher in vivo anti-tumor efficacy over those of vaccinated normal mice.

CONCLUSIONThis study suggests that vaccination of RLM could elicit augmented antitumor immunity compared to normal hosts, highlighting the potential clinical benefit of performing tumor vaccination during irradiation or chemotherapeutics-induced lymphopenia in cancer patients.

Animals ; CD8-Positive T-Lymphocytes ; immunology ; Cancer Vaccines ; therapeutic use ; Cyclophosphamide ; adverse effects ; Female ; Granulocyte-Macrophage Colony-Stimulating Factor ; immunology ; Immunotherapy, Adoptive ; methods ; Lymphopenia ; etiology ; therapy ; Melanoma, Experimental ; drug therapy ; immunology ; radiotherapy ; Mice ; Mice, Inbred C57BL ; Whole-Body Irradiation

PURPOSE: This study was undertaken to retrospectively evaluate white blood cell kinetics, especially lymphocyte depression after different treatments, and to find the correlation between immunosuppression and large blood volume and dynamic blood flow within the mediastinal radiotherapy (RT) field in lung cancer. MATERIALS AND METHODS: Thirty-four patients with lung cancer were retrospectively evaluated; 10 patients had only radiotherapy (RT group), 8 had chemotherapy (CT group) and 16 had chemotherapy and radiotherapy (RT/CT group). The mean follow-up periods of the RT-including groups (RT group and RT/CT group) and the RT-excluding group (CT group) were 6 and 8 months, respectively. Complete blood cell counts including lymphocyte percentage (%) were checked weekly during RT but less frequently during CT and after RT. RESULTS: Changes in total white blood cell counts were not significantly different among the three groups. The lymphocyte count and lymphocyte % were much lower in the RT-including groups than in the RT- excluding group. The difference between pre-treatment and final lymphocyte count and the difference between pre-treatment and final lymphocyte % were significant (p=0.044 and p=0.037) between the RT- including groups and the RT-excluding group. CONCLUSION: Lymphopenia was more marked after treatment containing RT than CT only. Lymphopenia may be one cause of a compromised immune system after mediastinal irradiation in lung cancer. We suggest cautiously that previous studies showing evidence of lymphocyte apoptosis after low-dose irradiation and large blood volume and dynamic blood flow within the RT fields could be somewhat related to lymphopenia after mediastinal irradiation.
Apoptosis ; Blood Cell Count ; Blood Volume ; Depression ; Drug Therapy ; Follow-Up Studies ; Humans ; Immune System ; Immunosuppression ; Kinetics ; Leukocyte Count ; Leukocytes ; Lung Neoplasms* ; Lung* ; Lymphocyte Count ; Lymphocytes ; Lymphopenia* ; Radiotherapy ; Retrospective Studies

The aim of this study was to identify the risk factors associated with severe bacterial infection (SBI) in multiple myeloma (MM) patients during treatment with bortezomib-based regimens. A total of 98 patients with MM were evaluated during 427 treatment courses. SBI occurred in 57.1% (56/98) of the patients and during 19.0% (81/427) of the treatment courses. In the multivariate analysis for the factors associated with the development of SBI in each treatment course, poor performance status (Eastern Cooperative Oncology Group ≥ 2, P < 0.001), early course of therapy (≤ 2 courses, P < 0.001), and pretreatment lymphopenia (absolute lymphocyte count < 1.0 × 10(9)/L, P = 0.043) were confirmed as independent risk factors. The probability of developing SBI were 5.1%, 14.9%, 23.9% and 59.5% in courses with 0, 1, 2, and 3 risk factors, respectively (P < 0.001). In conclusion, we identified three pretreatment risk factors associated with SBI in each course of bortezomib treatment. Therefore, MM patients with these risk factors should be more closely monitored for the development of SBI during bortezomib-based treatment.
Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Bacterial Infections/*complications/microbiology ; Bortezomib/*administration & dosage ; Female ; Gram-Negative Bacteria/isolation & purification ; Gram-Positive Bacteria/isolation & purification ; Humans ; Lymphocyte Count ; Lymphopenia/*therapy ; Male ; Middle Aged ; Multiple Myeloma/complications/*drug therapy/mortality ; Multivariate Analysis ; Proportional Hazards Models ; Retrospective Studies ; Risk Factors ; Stem Cell Transplantation ; Survival Rate ; Transplantation, Homologous

OBJECTIVE: This study summarizes and compares clinical and laboratory characteristics of 34 patients admitted to the intensive care unit (ICU) for complications from coronavirus disease 2019 (COVID-19) at the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China from Jan. 22 to Mar. 5, 2020. METHODS: A total of 34 patients were divided into two groups, including those who required noninvasive ventilation (NIV) and invasive mechanical ventilation (IMV) with additional extracorporeal membrane oxygenation (ECMO) in 11 patients. Clinical features of COVID-19 patients were described and the parameters of clinical characteristics between the two groups were compared. RESULTS: The rates of the acute cardiac and kidney complications were higher in IMV cases than those in NIV cases. Most patients had lymphocytopenia on admission, with lymphocyte levels dropping progressively on the following days, and the more severe lymphopenia developed in the IMV group. In both groups, T lymphocyte counts were below typical lower limit norms compared to B lymphocytes. On admission, both groups had higher than expected amounts of plasma interleukin-6 (IL-6), which over time declined more in NIV patients. The prothrombin time was increased and the levels of platelet, hemoglobin, blood urea nitrogen (BUN), D-dimer, lactate dehydrogenase (LDH), and IL-6 were higher in IMV cases compared with NIV cases during hospitalization. CONCLUSIONS Data showed that the rates of complications, dynamics of lymphocytopenia, and changes in levels of platelet, hemoglobin, BUN, D-dimer, LDH and IL-6, and prothrombin time in these ICU patients were significantly different between IMV and NIV cases.
Acute Kidney Injury ; virology ; Aged ; Aged, 80 and over ; Betacoronavirus ; Blood Urea Nitrogen ; China ; Coronavirus Infections ; complications ; therapy ; Extracorporeal Membrane Oxygenation ; Female ; Fibrin Fibrinogen Degradation Products ; analysis ; Heart Diseases ; virology ; Hemoglobins ; analysis ; Hospitalization ; Humans ; Intensive Care Units ; Interleukin-6 ; blood ; L-Lactate Dehydrogenase ; blood ; Lymphopenia ; virology ; Male ; Middle Aged ; Noninvasive Ventilation ; Pandemics ; Pneumonia, Viral ; complications ; therapy ; Positive-Pressure Respiration ; Prothrombin Time ; Retrospective Studies

The majority of Korean patients with pandemic influenza A (H1N1) during the 2009 epidemic were under 20 yr of age. The limited data on the clinical characteristics of these children led us to conduct a case note-based investigation of children admitted to 6 university hospitals with 2009 H1N1 influenza. A total of 804 children was enrolled. The median age was 5 yr; 63.8% were males; and 22.4% had at least one chronic underlying disease. Ninety-five of the patients (11.8%) were critically ill and they suffered more from shortness of breath, dyspnea and lymphopenia than the other patients. Among all the patients, 98.8% were treated with antivirals and 73% received treatment within 48 hr of illness onset. All the enrolled patients are alive and appear to have had good outcomes, probably due to the early intervention and antiviral treatment. This study deals with hospitalized children whose diagnoses of influenza A (H1N1) were confirmed, and therefore provides important new information about the clinical patterns of children with influenza A (H1N1) in Korea.
Adolescent ; Antiviral Agents/therapeutic use ; Child ; Child, Hospitalized ; Child, Preschool ; Critical Illness ; Dyspnea/etiology ; Female ; Humans ; Infant ; Infant, Newborn ; Influenza A Virus, H1N1 Subtype/genetics/*isolation & purification ; Influenza, Human/*diagnosis/drug therapy/epidemiology ; Lymphopenia/etiology ; Male ; Oseltamivir/therapeutic use ; Pandemics ; Republic of Korea/epidemiology ; Retrospective Studies

This study was performed to characterize respiratory viral infections in pediatric patients undergoing hematopoietic stem cell transplantation (HSCT). Study samples included 402 respiratory specimens obtained from 358 clinical episodes that occurred in the 116 children of the 175 consecutive HSCT cohort at Seoul National University Children's Hospital, Korea from 2007 to 2010. Multiplex reverse-transcription polymerase chain reactions were performed for rhinovirus, respiratory syncytial virus (RSV), parainfluenza viruses (PIVs), adenovirus, human coronavirus (hCoV), influenza viruses and human metapneumovirus. Viruses were identified in 89 clinical episodes that occurred in 58 patients. Among the 89 clinical episodes, frequently detected viruses were rhinovirus in 25 (28.1%), RSV in 23 (25.8%), PIV-3 in 16 (18.0%), adenovirus in 12 (13.5%), and hCoV in 10 (11.2%). Lower respiratory tract infections were diagnosed in 34 (38.2%). Neutropenia was present in 24 (27.0%) episodes and lymphopenia was in 31 (34.8%) episodes. Sixty-three percent of the clinical episodes were hospital-acquired. Three patients died of respiratory failure caused by respiratory viral infections. Respiratory viral infections in pediatric patients who have undergone HSCT are common and are frequently acquired during hospitalization. Continuous monitoring is required to determine the role of respiratory viruses in immunocompromised children and the importance of preventive strategies.
Adenoviridae/genetics/isolation & purification ; Adolescent ; Adult ; Child ; Child, Preschool ; Cohort Studies ; Coronavirus/genetics/isolation & purification ; Female ; *Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells/cytology ; Hospitalization ; Humans ; Infant ; Lymphopenia/epidemiology ; Male ; Neutropenia/epidemiology ; Parainfluenza Virus 3, Human/genetics/isolation & purification ; Prevalence ; Respiratory Syncytial Viruses/genetics/isolation & purification ; Respiratory Tract Infections/epidemiology/therapy/*virology ; Reverse Transcriptase Polymerase Chain Reaction ; Rhinovirus/genetics/isolation & purification ; Seasons ; Young Adult