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1.
Viruses ; 15(2)2023 01 28.
Article in English | MEDLINE | ID: covidwho-2216973

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) is the most transmissible ß-coronavirus in history, affecting all population groups. Immunocompromised patients, particularly cancer patients, have been highlighted as a reservoir to promote accumulation of viral mutations throughout persistent infection. CASE PRESENTATION: We aimed to describe the clinical course and SARS-CoV-2 mutation profile for 102 days in an immunocompromised patient with non-Hodgkin's lymphoma and COVID-19. We used RT-qPCR to quantify SARS-CoV-2 viral load over time and whole-virus genome sequencing to identify viral lineage and mutation profile. The patient presented with a persistent infection through 102 days while being treated with cytotoxic chemotherapy for non-Hodgkin's lymphoma and received targeted therapy for COVID-19 with remdesivir and hyperimmune plasma. All sequenced samples belonged to the BA.1.1 lineage. We detected nine amino acid substitutions in five viral genes (Nucleocapsid, ORF1a, ORF1b, ORF13a, and ORF9b), grouped in two clusters: the first cluster with amino acid substitutions only detected on days 39 and 87 of sample collection, and the second cluster with amino acid substitutions only detected on day 95 of sample collection. The Spike gene remained unchanged in all samples. Viral load was dynamic but consistent with the disease flares. CONCLUSIONS: This report shows that the multiple mutations that occur in an immunocompromised patient with persistent COVID-19 could provide information regarding viral evolution and emergence of new SARS-CoV-2 variants.


Subject(s)
COVID-19 , Lymphoma, Non-Hodgkin , Humans , SARS-CoV-2/genetics , COVID-19/diagnosis , Virus Shedding , Persistent Infection , Lymphoma, Non-Hodgkin/complications , Lymphoma, Non-Hodgkin/drug therapy , Immunocompromised Host
2.
Iran J Med Sci ; 48(1): 26-34, 2023 Jan.
Article in English | MEDLINE | ID: covidwho-2205675

ABSTRACT

Background: Non-Hodgkin lymphoma (NHL) is the eleventh leading cause of cancer-related death in the world. Diffuse large B-cell lymphoma (DLBCL) is the most common type of NHL. Up to winter 2021-2022, the death toll caused by the coronavirus disease 2019 (COVID-19) has exceeded 5.6 million worldwide. Possible molecular mechanisms involved in the systemic inflammation, and cytokine storm in COVID-19 patients are still not fully understood. MicroRNA-155 (miR-155) plays a role in the post-transcriptional gene regulation of hematopoiesis, oncogenesis, and inflammation. The present study aimed to evaluate the expression of miR-155 in patients with DLBCL and/or COVID-19. Methods: A cross-sectional study was conducted from July to December 2020 in Tehran (Iran) to evaluate the expression of miR-155 in adult patients diagnosed with DLBCL and/or COVID-19. The real-time polymerase chain reaction technique was used to evaluate the expression of miR-155 in the sera of 92 adults who were either healthy or suffering from DLBCL and/or COVID-19. Relative quantification of gene expression was calculated in terms of cycle threshold (Ct) value. Data were analyzed using SPSS software, and P<0.05 was considered statistically significant. Results: The expression of miR-155 was not associated with the sex or age of the participants. In comparison with healthy individuals (-ΔCt -1.92±0.25), the expression of miR-155 increased in patients with COVID-19 (1.95±0.14), DLBCL (2.25±0.16), or both (4.33±0.65). Conclusion: The expression of miR-155 increased in patients with DLBCL and/or COVID-19.


Subject(s)
COVID-19 , Lymphoma, Large B-Cell, Diffuse , Lymphoma, Non-Hodgkin , MicroRNAs , Adult , Humans , Cross-Sectional Studies , MicroRNAs/genetics , COVID-19/genetics , Iran/epidemiology , Lymphoma, Non-Hodgkin/complications , Lymphoma, Non-Hodgkin/genetics , Lymphoma, Large B-Cell, Diffuse/diagnosis , Lymphoma, Large B-Cell, Diffuse/genetics , Lymphoma, Large B-Cell, Diffuse/pathology
3.
Tumori ; 108(6): NP1-NP4, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-1582700

ABSTRACT

During the coronavirus disease 2019 (COVID-19) pandemic, oncologists have managed patients at higher risk of having a severe course of this infection. This raises new questions about their correct management, as well as the difficulty of distinguishing tumor/treatments complications from those related to COVID-19. We report a case of an 11-year-old boy undergoing treatment for T-cell lymphoblastic lymphoma who experienced a prolonged COVID-19 course. Oncologic therapy was continued without significant changes compared to the initially planned treatment. No relevant complications occurred. COVID-19 convalescent plasma was administered, resulting in a positive antibody titer after 24 days.


Subject(s)
COVID-19 , Lymphoma, Non-Hodgkin , Male , Child , Humans , COVID-19/complications , SARS-CoV-2 , Pandemics , Lymphoma, Non-Hodgkin/complications , Lymphoma, Non-Hodgkin/diagnosis , Lymphoma, Non-Hodgkin/therapy , COVID-19 Serotherapy
6.
BMC Infect Dis ; 21(1): 809, 2021 Aug 12.
Article in English | MEDLINE | ID: covidwho-1440906

ABSTRACT

BACKGROUND: The current literature is scarce as to the outcomes of COVID-19 infection in non-Hodgkin's lymphoma patients and whether immunosuppressive or chemotherapeutic agents can cause worsening of the patients' condition during COVID-19 infection. CASE PRESENTATION: Our case is a 59-year-old gentleman who presented to the Emergency Department of the Cancer Institute of Hospital das Clínicas da Universidade de São Paulo, São Paulo, Brazil on 10th May 2020 with a worsening dyspnea and chest pain which had started 3 days prior to presentation to the Emergency Department. He had a past history of non-Hodgkin's lymphoma for which he was receiving chemotherapy. Subsequent PCR testing demonstrated that our patient was SARS-CoV-2 positive. CONCLUSION: In this report, we show a patient with non-Hodgkin lymphoma in the middle of chemotherapy, presented a mild clinical course of COVID-19 infection.


Subject(s)
COVID-19 , Lymphoma, Non-Hodgkin , Brazil , Humans , Immunosuppressive Agents , Lymphoma, Non-Hodgkin/complications , Lymphoma, Non-Hodgkin/drug therapy , Male , Middle Aged , SARS-CoV-2
7.
Transfus Apher Sci ; 60(5): 103200, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1284583

ABSTRACT

Psoriasis is a chronic inflammatory skin disease that is characterized by well-demarcated erythematous plaques with a silver scale. Although many new and emerging therapeutic agents are often sufficient to control the disease, there is still a need for alternative treatment options in challenging cases. Extracorporeal photopheresis (ECP) has been applied to many T-cell-mediated diseases to restore immune homeostasis and treat psoriasis effectively. In this paper, we present a psoriasis patient who did not respond to methotrexate, narrowband ultraviolet B, or acitretin. Because of a diagnosis of non-Hodgkin lymphoma, the patient had contraindications for cyclosporine, fumaric acid esters, and biologics but achieved remission with a total of 12 sessions of ECP in two and a half months. Although exacerbation was recorded after polymerase chain reaction (PCR) confirmed coronavirus 2019 (COVID-19) disease infection at the end of the first month, scores from the psoriasis area severity index (PASI) and dermatological life quality index (DLQI) were regressed significantly within two and a half months. ECP seems to provide an effective and rapid response for psoriasis and should be considered for psoriasis patients who fail to respond or have contraindications to existing treatments.


Subject(s)
COVID-19/complications , Lymphoma, Non-Hodgkin/complications , Pandemics , Photopheresis , Psoriasis/drug therapy , SARS-CoV-2 , Acitretin/therapeutic use , Chemical and Drug Induced Liver Injury/etiology , Combined Modality Therapy , Contraindications, Drug , Cyclosporine/adverse effects , Humans , Male , Methotrexate/adverse effects , Methotrexate/therapeutic use , Middle Aged , Nails/pathology , Psoriasis/complications , Psoriasis/pathology , Psoriasis/radiotherapy , Quality of Life , Severity of Illness Index , Ultraviolet Therapy
8.
Blood Cancer J ; 11(6): 115, 2021 06 16.
Article in English | MEDLINE | ID: covidwho-1275905
10.
Am J Hematol ; 96(8): 934-944, 2021 08 01.
Article in English | MEDLINE | ID: covidwho-1204615

ABSTRACT

Prolonged Covid-19 is an emerging issue for patients with lymphoma or immune deficiency. We aimed to examine prolonged length of in-hospital stay (LOS) due to Covid-19 among patients with lymphoma and assess its determinants and outcomes. Adult patients with lymphoma admitted for Covid-19 to 16 French hospitals in March and April, 2020 were included. Length of in-hospital stay was analyzed as a competitor vs death. The study included 111 patients. The median age was 65 years (range, 19-92). Ninety-four patients (85%) had B-cell non-Hodgkin lymphoma. Within the 12 months prior to hospitalization for Covid-19, 79 patients (71%) were treated for their lymphoma. Among them, 63 (57%) received an anti-CD20 therapy. Fourteen patients (12%) had relapsed/refractory disease. The median LOS was 14 days (range, 1-235). After a median follow-up of 191 days (3-260), the 6-month overall survival was 69%. In multivariable analyses, recent administration of anti-CD20 therapy was associated with prolonged LOS (subdistribution hazard ratio 2.26, 95% confidence interval 1.42-3.6, p < 0.001) and higher risk of death (hazard ratio 2.17, 95% confidence interval 1.04-4.52, p = 0.039). An age ≥ 70 years and relapsed/refractory lymphoma were also associated with prolonged LOS and decreased overall survival. In conclusion, an age ≥ 70 years, a relapsed/refractory lymphoma and recent administration of anti-CD20 therapy are risk factors for prolonged LOS and death for lymphoma patients hospitalized for Covid-19. These findings may contribute to guide the management of lymphoma during the pandemic, support evaluating specific therapeutic approaches, and raise questions on the efficacy and timing of vaccination of this particular population.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , B-Lymphocytes/drug effects , COVID-19/complications , Immunotherapy/adverse effects , Length of Stay/statistics & numerical data , Lymphoma, Non-Hodgkin/complications , SARS-CoV-2 , Adult , Age Factors , Aged , Aged, 80 and over , Antigens, CD20/immunology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , COVID-19/mortality , Combined Modality Therapy , Comorbidity , Drug Resistance, Neoplasm , Female , Humans , Lymphoma, Non-Hodgkin/mortality , Lymphoma, Non-Hodgkin/therapy , Male , Middle Aged , Proportional Hazards Models , Retrospective Studies , Risk Factors , Rituximab/administration & dosage , Rituximab/adverse effects , Survival Analysis , Young Adult
11.
Neurol Sci ; 42(6): 2523-2525, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1068743

ABSTRACT

BACKGROUND: Paraneoplastic Cerebellar degeneration (PCD) is one of the classical paraneoplastic syndromes (PNS) which is characterised by subacute onset, progressive cerebellar ataxia and is usually associated with small cell lung carcinoma, adeno carcinoma of breast and ovary followed by Hodgkin's lymphoma. OBJECTIVE: We herein report a case of subacute onset, progressive cerebellar ataxia in a 37-year-old female, who on evaluation was found to have non-Hodgkin's lymphoma and experienced good clinical response to treatment. DISCUSSION: As compared to solid tumours, chances of association of PNS with Lymphomas is quite low and there are only few case reports in the literature showing association of PCD with non-Hodgkin's lymphoma. As PCD is one of the classical PNS, it is very important to identify subtle cerebellar manifestations in an otherwise apparently normal individual, as early diagnosis and aggressive treatment can immensely improve the mortality and morbidity associated with this syndrome. CONCLUSION: This case signifies the importance of suspecting PNS as an important differential diagnosis in a young patient presenting with subacute onset progressive cerebellar ataxia and evaluating her extensively for malignancy in spite of no paraneoplastic antibody been detected as early diagnosis and treatment can lead to gratifying response. We do agree that 2 weeks follow up is a short time interval to determine whether the response was sustained or not, for which a long term follow up is required.


Subject(s)
Cerebellar Ataxia , Hodgkin Disease , Lymphoma, Non-Hodgkin , Paraneoplastic Cerebellar Degeneration , Adult , Cerebellum , Female , Humans , Lymphoma, Non-Hodgkin/complications , Lymphoma, Non-Hodgkin/diagnosis , Paraneoplastic Cerebellar Degeneration/diagnosis
12.
Eur Rev Med Pharmacol Sci ; 24(22): 11926-11933, 2020 11.
Article in English | MEDLINE | ID: covidwho-962026

ABSTRACT

OBJECTIVE: Hematologic cancer patients with Coronavirus Disease 2019 (COVID-19) tend to have a more serious disease course than observed in the general population. Herein, we comprehensively reviewed existing literature and analyzed clinical characteristics and mortality of patients with hematologic malignancies and COVID-19. MATERIALS AND METHODS: Through searching PubMed until June 03, 2020, we identified 16 relevant case studies (33 cases) from a total of 45 studies that have reported on patients with COVID-19 and hematologic malignancies. We investigated the clinical and laboratory characteristics including type of hematologic malignancies, initial symptoms, laboratory findings, and clinical outcomes. Then, we compared those characteristics and outcomes of patients with hematologic malignancies and COVID-19 to the general population infected with COVID-19. RESULTS: The median age was 66-year-old. Chronic lymphocytic leukemia was the most common type of hematologic malignancy (39.4%). Fever was the most common symptom (75.9%). Most patients had normal leukocyte counts (55.6%), lymphocytosis (45.4%), and normal platelet counts (68.8%). In comparison to patients with COVID-19 without underlying hematologic malignancies, dyspnea was more prevalent (45.0 vs. 24.9%, p=0.025). Leukocytosis (38.9 vs. 9.8%, p=0.001), lymphocytosis (45.4 vs. 8.2%, p=0.001), and thrombocytopenia (31.3 vs. 11.4%, p=0.036) were significantly more prevalent and lymphopenia (18.2 vs. 57.4%, p=0.012) less prevalent in patients with hematologic malignancies. There were no clinical and laboratory characteristics predicting mortality in patients with hematologic malignancies. Mortality was much higher in patients with hematologic malignancies compared to those without this condition (40.0 vs. 3.6%, p<0.001). CONCLUSIONS: Co-occurrence of hematologic malignancies and COVID-19 is rare. However, due to the high mortality rate from COVID-19 in this vulnerable population, further investigation on tailored treatment and management is required.


Subject(s)
COVID-19/complications , Dyspnea/physiopathology , Hematologic Neoplasms/complications , Lymphocytosis/blood , Lymphopenia/blood , Thrombocytopenia/blood , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/blood , COVID-19/mortality , COVID-19/physiopathology , Child , Child, Preschool , Dyspnea/epidemiology , Female , Fever/epidemiology , Fever/physiopathology , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/complications , Leukocytosis/blood , Leukocytosis/epidemiology , Lymphocytosis/epidemiology , Lymphoma, Non-Hodgkin/complications , Lymphopenia/epidemiology , Male , Middle Aged , Multiple Myeloma/complications , Thrombocytopenia/epidemiology , Young Adult
13.
Biomedica ; 40(Supl. 2): 27-33, 2020 10 30.
Article in English, Spanish | MEDLINE | ID: covidwho-916544

ABSTRACT

COVID-19 is the viral infection caused by SARS-CoV-2 declared by the World Health Organization (WHO) as a pandemic. Patients with cancer have a higher risk to acquire the infection and worse prognosis as they have to attend more medical visits in healthcare institutions, receive medical and surgical treatments, and be subjected to diagnostic studies such as PET/CT in nuclear medicine services where the infection may be an incidental finding. We present here F18-FDG PET/CT (Positron Emission Tomography and Computed Tomography with 2-deoxy-2-[fluorine-18]fluoro-D-glucose), images with findings of COVID-19 from patients with different oncological conditions but no respiratory symptoms.


La COVID-19 es la infección viral causada por el SARS-CoV-2 y declarada por la Organización Mundial de la Salud (OMS) como pandemia. Los pacientes con cáncer tienen un mayor riesgo de adquirir la infección y un peor pronóstico, ya que deben asistir a visitas médicas en diferentes centros hospitalarios, reciben tratamientos médicos y quirúrgicos y deben someterse a estudios diagnósticos como la PET/CT en servicios de medicina nuclear, lo que es ocasión para el hallazgo incidental de la infección. Se presentan las imágenes de tomografías computarizadas por emisión de positrones con 18-fluorodesoxiglucosa (F18) (Positron Emission Tomography and Computed Tomography with 2-deoxy-2-[fluorine-18]fluoro-D-glucose, PET/CT F18-FDG) en las que se evidenció la COVID-19 en pacientes con diversas enfermedades oncológicas, pero sin sintomatología respiratoria.


Subject(s)
Betacoronavirus/isolation & purification , Coronavirus Infections/diagnostic imaging , Incidental Findings , Neoplasms/complications , Pneumonia, Viral/diagnostic imaging , Positron Emission Tomography Computed Tomography , Adult , Aged , Asymptomatic Diseases , COVID-19 , COVID-19 Testing , Carcinoma, Signet Ring Cell/complications , Carcinoma, Signet Ring Cell/diagnostic imaging , Carcinoma, Signet Ring Cell/secondary , Clinical Laboratory Techniques , Coronavirus Infections/complications , Coronavirus Infections/diagnosis , Female , Fluorine Radioisotopes , Fluorodeoxyglucose F18 , Humans , Lymphatic Metastasis/diagnostic imaging , Lymphoma, Non-Hodgkin/complications , Lymphoma, Non-Hodgkin/diagnostic imaging , Male , Middle Aged , Neoplasms/diagnostic imaging , Pandemics , Pleural Effusion/diagnostic imaging , Pleural Effusion/etiology , Pneumonia, Viral/complications , Radiopharmaceuticals , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2 , Seminoma/complications , Seminoma/diagnostic imaging , Seminoma/secondary , Stomach Neoplasms
15.
Am J Case Rep ; 21: e927812, 2020 Oct 03.
Article in English | MEDLINE | ID: covidwho-854653

ABSTRACT

BACKGROUND This is a case report of an immunocompromised patient with a history of non-Hodgkin lymphoma and persistent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection who was seronegative and successfully treated with convalescent plasma. CASE REPORT A 63-year-old woman with a past medical history of non-Hodgkin lymphoma in remission while on maintenance therapy with the anti-CD20 monoclonal antibody, obinutuzumab, tested positive for SARS-CoV-2 via nasopharyngeal reverse transcription polymerase chain reaction (RT-PCR) testing over 12 weeks and persistently tested seronegative for immunoglobulin G (IgG) antibodies using SARS-CoV-2 IgG chemiluminescent microparticle immunoassay technology. During this time, the patient experienced waxing and waning of symptoms, which included fever, myalgia, and non-productive cough, but never acquired severe respiratory distress. She was admitted to our hospital on illness day 88, and her symptoms resolved after the administration of convalescent plasma. CONCLUSIONS As the understanding of the pathogenesis of SARS-CoV-2 continues to evolve, we can currently only speculate about the occurrence of chronic infection vs. reinfection. The protective role of antibodies and their longevity against SARS-CoV-2 remain unclear. Since humoral immunity has an integral role in SARS-CoV-2 infection, various phase 3 vaccine trials are underway. In the context of this pandemic, the present case demonstrates the challenges in our understanding of testing and treating immunocompromised patients.


Subject(s)
Antibodies, Monoclonal, Humanized/administration & dosage , Coronavirus Infections/complications , Coronavirus Infections/diagnosis , Immunocompromised Host , Lymphoma, Non-Hodgkin/immunology , Pneumonia, Viral/complications , Pneumonia, Viral/diagnosis , Antineoplastic Agents, Immunological/administration & dosage , COVID-19 , COVID-19 Testing , Clinical Laboratory Techniques/methods , Coronavirus Infections/therapy , Female , Follow-Up Studies , Humans , Immunization, Passive/methods , Lymphoma, Non-Hodgkin/complications , Lymphoma, Non-Hodgkin/drug therapy , Middle Aged , Pandemics , Real-Time Polymerase Chain Reaction/methods , Serologic Tests/methods , Severity of Illness Index , Treatment Outcome , COVID-19 Serotherapy
16.
J Infect Chemother ; 27(1): 99-102, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-753271

ABSTRACT

We present three patients affected by pulmonary squamous cell carcinoma, metastatic esophageal cancer and advanced non-Hodgkin lymphoma, who incurred in coronavirus 2019 (COVID-19) infection during the early phase of epidemic wave in Italy. All patients presented with fever. Social contact with subject positive for COVID-19 was declared in only one of the three cases. In all cases, laboratory findings showed lymphopenia and elevated C-reactive protein (CRP). Chest x-ray and computed tomography showed bilateral ground-glass opacities, shadowing, interstitial abnormalities, and "crazy paving" pattern which evolved with superimposition of consolidations in one patient. All patients received antiviral therapy based on ritonavir and lopinavir, associated with hydroxychloroquine. Despite treatment, two patients with advanced cancers died after 39 and 17 days of hospitalization, while the patient with lung cancer was dismissed at home, in good conditions.


Subject(s)
Coronavirus Infections/drug therapy , Hydroxychloroquine/therapeutic use , Lopinavir/therapeutic use , Neoplasms/complications , Pneumonia, Viral/drug therapy , Ritonavir/therapeutic use , Aged , Anti-Bacterial Agents/therapeutic use , Antiviral Agents/therapeutic use , Betacoronavirus , COVID-19 , Carcinoma, Squamous Cell/complications , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/drug therapy , Coronavirus Infections/complications , Coronavirus Infections/diagnosis , Disease Outbreaks , Drug Therapy, Combination , Esophageal Neoplasms/complications , Esophageal Neoplasms/diagnosis , Esophageal Neoplasms/drug therapy , Fatal Outcome , Humans , Italy , Lung Neoplasms/complications , Lung Neoplasms/diagnosis , Lung Neoplasms/drug therapy , Lymphoma, Non-Hodgkin/complications , Lymphoma, Non-Hodgkin/diagnosis , Lymphoma, Non-Hodgkin/drug therapy , Male , Middle Aged , Neoplasms/diagnosis , Neoplasms/drug therapy , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/diagnosis , SARS-CoV-2 , Tomography, X-Ray Computed , Treatment Outcome
17.
J Thromb Haemost ; 18(9): 2202-2204, 2020 09.
Article in English | MEDLINE | ID: covidwho-593310

ABSTRACT

COVID-19 can be associated with coagulopathy (CAC, COVID-19-associated coagulopathy) with a high prothrombotic risk based on an intense inflammatory response to viral infection leading to immunothrombosis through different procoagulant pathways. Emerging evidence suggests that the use of heparin in these patients could be associated with lower mortality. Emicizumab is a bispecific humanized monoclonal antibody that bridges activated factor IX and factor X, thereby restoring the function of missing factor VIIIa in hemophilia A. The use of emicizumab has been associated with thrombotic events in patients who also received high cumulative amounts of activated prothrombin complex concentrates. Although this risk is extremely low, there is a lack of evidence on whether CAC increases the thrombotic risk in patients on emicizumab prophylaxis. We present the case of a patient with severe hemophilia A in prophylaxis treatment with emicizumab; due to the potential thrombotic risk we decided to administer low molecular weight heparin as prophylaxis treatment without any thrombotic or bleeding complications.


Subject(s)
Antibodies, Bispecific/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/complications , Hemophilia A/complications , Hemophilia A/drug therapy , Venous Thromboembolism/prevention & control , Anticoagulants/therapeutic use , Blood Coagulation , Coagulants , Factor IXa/chemistry , Factor X/chemistry , Follow-Up Studies , HIV Infections/complications , Hepatitis C/complications , Humans , Inflammation , Lymphoma, Non-Hodgkin/complications , Male , Middle Aged , Thrombosis , Venous Thromboembolism/drug therapy
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