Prise en charge des hémopathies malignes au centre national d'oncologie médicale et de radiothérapie Alassane Ouattara d'Abidjan / Managem ent of hem atologic neoplasm sat the Centre National d'Oncologie Médicale et de Radiothérapie Alassane Ouattara ofAbidjan

Introduction. Les hémopathies malignes sont des proliférations anormales et anarchiques de cellules hématopoïétiques à point de départ médullaire ou périphérique. Notre étude qui avait pour objectif de faire le bilan de la prise en charge des hémopathies malignes au Centre national d'oncologie médical et de radiothérapie Alassane Ouattara. Méthodes. Il s'agissait d'une étude rétrospective descriptive d'une durée de 2 ans 3 mois allant du 1er janvier 2018 au 31 Mars 2020 portant sur 80 dossiers de malades porteurs d'hémopathies malignes et prise en charge dans le centre. Résultats. Notre étude a permis de recenser 2,2% d'hémopathies malignes sur les 3650 cas de pathologies cancéreuses recensées au CNRAO, soit une incidence 26,66 cas/an avec un sex-ratio 1,2. Les syndromes lymphoprolifératifs (SLP) sont les plus fréquents (96,25 %), sous trois principales formes: lymphomes malins non hodgkiniens (LMNH) non Burkitt (51,25%), leucémie myéloïde chronique (20%) et le myélome multiple (16,25%). Les LMNH représentent 51,25% des HM recensées avec 41,46 % de lymphomes de haut grade de malignité. La chimiothérapie était de mise chez tous nos patients. Ainsi sur 41 cas de LMNH, seulement 12 (29,27%) ont bénéficié du protocole R-CHOP. On notait 46,34% de réponse complète. Dans notre étude, le LH représentait 8,75% il était traité à 71,43% avec le protocole ABVD avec une réponse complète chez 6 patients. 37,5% des patients porteurs de leucémie myéloïde chronique ont reçu le Rituximab; ils ont été traités par les protocoles COP (31,25%), CHOP (31,25%), RCVP (12,5%) et R-CHOP (25%). La réponse thérapeutique était complète à 68,75%. Le protocole utilisé dans le traitement du myélome multiple a été le VMCD-REV à 76,92% avec pour réponse thérapeutique complète chez 6 patients, 3 réponses partielles et 4 en cours de traitement. Conclusion. Les SLP qui sont les plus fréquents des HM avec trois principales formes: LMNH non Burkitt, leucémie myéloïde chronique et myélome multiple. Nous avons cependant des difficultés quant à la mise en route de la chimiothérapie.

Introduction. Hematologic neoplasms are abnormal and anarchic proliferations of hematopoietic cells with a medullary or peripheral starting point. Our study aimed to report the management of hematological malignancies at the Centre National d'Oncologie Médicale et de Radiothérapie Alassane Ouattara (CNRAO). Methods. This was a descriptive retrospective study lasting 2 years 3 months from January 1st, 2018 to March 31st, 2020 concerning 80 patients with hematologic neoplasms who were managed in the CNRAO. Results. Hematologic neoplasms represented 2.2% of cancers (80/3650) at CNRAO, giving an annual incidence of 26.66 cases. The sex ratio was 1.2. Lymphoproliferative syndromes were the most common subgroups (96.25%). These were mainly non-Burkitt non Hodgkin lymphoma (51.25%), high grade lymphomas (41.46%), chronic lymphocytic lymphoma (20%) and multiple myeloma (16.25%). Chemotherapy was administered to all patients. Among 41 cases of non-Hodgkin lymphoma, 12 (29.27%) benefited from the R-CHOP protocol and full response was observed in 46.34% of them. We found 7 patients with Hodgkin lymphoma (8.75%) and the ABVD protocol was used for 6 cases (71.43%). Six out of these seven patients were in complete response. Among the 16 patients with chronic lymphocytic leukemia, 6 (37.5%) received Rituximab. The distribution of the patients with chronic lymphocytic leukemia was as follows: COP 31.25%, CHOP 31.25%, RCVP 12.5% and R-CHOP 25% and 68.75% had full response. The most common treatment protocol for multiple myeloma was VMCD-REV (76.92%). Six patients had complete response, 3 had partial response and 4 were in the course of treatment. Conclusion. In our practice, hematologic neoplasms are mainly lymphoproliferative syndromes and the most common varieties are non-Burkitt non Hodgkin lymphoma, high grade lymphomas, chronic lymphocytic lymphoma and multiple myeloma. We have difficulties in getting chemotherapy started.

Hallazgos incidentales en cirugía abdominal: masas y sarcomas retroperitoneales / Incidental findings in abdominal surgery: Retroperitoneal masses and sarcomas

Introducción. El retroperitoneo es una estructura que se extiende desde el diafragma hasta la pelvis, está delimitado adelante por el peritoneo parietal, atrás y a los lados por la fascia transversalis y se divide en 9 compartimientos. Se pueden encontrar lesiones primarias o secundarias, cuya evolución clínica varía desde un curso indolente hasta rápidamente progresivo, tanto local como a distancia. Su enfoque, desde el hallazgo hasta el tratamiento, es fundamental para el desenlace oncológico. Objetivo. Analizar la evaluación, el diagnóstico y el tratamiento de las masas retroperitoneales halladas incidentalmente y brindar un algoritmo de manejo. Métodos. Se hizo búsqueda en bases de datos como PubMed y MedicalKey de literatura referentes a tumores retroperitoneales, su diagnóstico y enfoque terapéutico, con el fin de presentar una revisión sobre el abordaje de las masas retroperitoneales y dar nuestras opiniones. Resultados. Se revisaron 43 referencias bibliográficas internacionales y nacionales, y se seleccionaron 20 de ellas, de donde se obtuvieron datos actualizados, recomendaciones de guías internacionales y experiencias nacionales, con lo cual se estructuró este manuscrito. Conclusiones. Las masas retroperitoneales abarcan un espectro de patologías que establecen un reto diagnóstico por su origen embriológico, localización y baja frecuencia. El diagnostico histológico es de vital importancia desde el inicio, para conocer la evolución natural de la enfermedad, y el manejo multidisciplinario en centros de referencia es fundamental para impactar en los desenlaces oncológicos. Existen variadas modalidades terapéuticas, como quimioterapia, radioterapia y resección quirúrgica con estándares oncológicos

Introduction. The retroperitoneum is an structure that extends from the diaphragm to the pelvis, bounded anteriorly by the parietal peritoneum, posteriorly and laterally by the transversalis fascia, and it is divided into 9 compartments. We can find primary or secondary lesions whose clinical evolution varies from an indolent course to a rapidly progressive one, both local and distant. Its approach from discovery to diagnosis and treatment is essential for the oncological outcomes. Objective. To analyze the evaluation, diagnosis and treatment of incidental retroperitoneal masses according to their origin and to provide a management algorithm. Methods. An updated literature search was carried out in databases such as PubMed and Medical Key on retroperitoneal tumors, therapeutic approach and diagnosis, obtaining national and international information to carry out a review article on the approach to retroperitoneal masses.Results. Forty-three international and national bibliographic references were reviewed, based on 20 updated data, recommendations from international guidelines and national experiences were obtained, with which a review and opinion manuscript was structured.Conclusions. Retroperitoneal masses cover a spectrum of pathologies that establish a diagnostic challenge due to their embryological origin, location and low frequency. Histological diagnosis is of vital importance from the beginning to know the natural evolution of the disease and multidisciplinary management in reference centers is essential to impact oncological outcomes. There are many therapeutic modalities from chemotherapy, radiotherapy and surgical resection with oncological standards

Anal canal lymphoma: Case report and literature review / Linfoma de canal anal, reporte de caso y revisión de la literatura

Abstract Introduction: Primary tumors of the anal canal other than carcinomas are rare entities; among them, anal canal lymphomas are extremely unusual and pose both a diagnostic and therapeutic challenge for the coloproctologist. Case presentation: A male patient with positive human immunodeficiency virus (HIV) with proctalgia and mass sensation at the perianal level. A concentric thickening of the walls of the lower rectum was documented by magnetic resonance imaging, with colonoscopy and biopsies with histopathology compatible with plasmablastic lymphoma. Therefore, a diverting colostomy was performed and, subsequently, the hematology service indicated chemotherapy with the EPOCH scheme. Discussion: Lymphoma of the anus represents 0.2 % of anorectal tumors, most of these are non-Hodgkin's lymphomas; Hodgkin's disease at the anorectal level is even rarer. The population with the highest risk of this entity is HIV-positive patients, such as the patient in this case, although other associated factors are described in the literature.

Resumen Introducción: los tumores primarios del canal anal diferentes a carcinomas son entidades poco frecuentes; dentro de estos, los linfomas del canal anal son extremadamente raros y generan un reto tanto diagnóstico como terapéutico para el coloproctólogo. Presentación de caso: se presenta a continuación un caso clínico de un paciente con virus de inmunodeficiencia humana (VIH) positivo con proctalgia y sensación de masa a nivel perianal, se documentó por resonancia magnética un engrosamiento concéntrico de las paredes del recto inferior, con realización de colonoscopia y biopsias con histopatología compatible con linfoma plasmablástico, por lo que se realizó una colostomía derivativa y, posteriormente, se indicó por el servicio de hematología una quimioterapia con esquema EPOCH. Discusión: el linfoma de ano representa el 0,2 % de los tumores anorrectales, la mayoría de estos corresponde a linfomas no Hodgkin, y es aún más rara la enfermedad de Hodgkin a nivel anorrectal. La población con mayor riesgo de presentar esta entidad es los pacientes con VIH positivo, como el paciente descrito en el caso, aunque existen otros factores asociados descritos en la literatura.

Linfoma cardiaco primario / Primary cardiac lymphoma

Los tumores cardíacos primarios son raros. Tienen una incidencia que varía entre 1,38 y 30 por 100.000 personas al año, un aproximado de 75-80 por ciento son benignos. El linfoma cardíaco primario representa el 1,3 por ciento de los tumores cardíacos primarios y el 0,5 por ciento de los linfomas extranodales. Se define como un linfoma no Hodgkin (LNH) que afecta solo al corazón y/o el pericardio. Su complejo sintomático puede incluir disnea, dolor torácico, fatiga progresiva, sudoración nocturna, pérdida ponderal, arritmias, síndrome de vena cava superior y un aproximado del 20 por ciento de los pacientes pueden desarrollar insuficiencia cardíaca aguda como primera manifestación. Sin embargo, la mayoría de ellos cursan con sintomatología inespecífica y son detectados de manera incidental. El linfoma no Hodgkin difuso de células B grandes es la variante histológica más frecuente. Presentamos un caso que inició con síntomas de insuficiencia cardiaca derecha, evolucionó desfavorable hasta su fallecimiento y se realizó el diagnóstico en la autopsia(AU)

Primary cardiac tumors are rare. They have an incidence that varies between 1.38 and 30 per 100,000 people per year, 75-80 percent are benign, approximately. Primary cardiac lymphoma represents 1.3 percent of primary cardiac tumors and 0.5 percent of extranodal lymphomas. It is defined as a non-Hodgkin's lymphoma (NHL) affecting only the heart and/or the pericardium. Its symptoms may include dyspnea, chest pain, progressive fatigue, night sweats, weight loss, arrhythmias, and superior vena cava syndrome. Approximately 20 percent of patients may develop acute heart failure as the first manifestation. However, most of them have nonspecific symptoms and are detected incidentally. Diffuse large B-cell non-Hodgkin's lymphoma is the most frequent histological variant. We report a case that began with symptoms of right heart failure, progressed unfavorably until death, and the diagnosis was made at autopsy(AU)

Experiencia en el uso de los protocolos Biomed-2 para el estudio de reordenamientos de TCR e inmunoglobulinas en proliferaciones linfoides en el Instituto Nacional de Cancerología, Colombia / Experience with the BIOMED-2 standardized polymerase chain reaction protocol for immunoglobulin and T- cell receptor clonality analysis in the Instituto Nacional de Cancerología, Colombia

Introducción. El consorcio europeo BIOMED-2 se creó para determinar si una población linfoide de difícil clasificación patológica es clonal. En Colombia, la implementación de estas pruebas comenzó en el 2015 en el Instituto Nacional de Cancerología E.S.E. (Bogotá). Objetivos. Determinar el comportamiento de las pruebas de reordenamiento clonal o clonalidad linfoide. y determinar las dificultades de su uso en nuestro medio verificando su adaptación local y los resultados en una serie retrospectiva de casos y consecutiva de proliferaciones linfoides sometidas a los protocolos BIOMED-2. Materiales y métodos. A partir de las historias clínicas, se recolectaron los datos clínicos e histológicos y los resultados de los análisis de los reordenamientos en todos los casos de proliferaciones linfoides sometidas a los protocolos BIOMED-2, entre febrero de 2015 y mayo de 2019. Resultados. Se hallaron 132 casos, de los cuales 47 se clasificaron mediante los protocolos de Biomed-2 como hiperplasias linfoides reactivas, 62 como linfomas T, 19 como linfomas B y 3 como neoplasias linfoides de linaje no establecido. Solo en un caso falló la extracción de ADN. Según estos resultados, la mayor dificultad diagnóstica para el patólogo fue el análisis de los infiltrados linfoides T, la mayoría (44) de los cuales correspondía a lesiones cutáneas. Conclusiones. Las pruebas de clonalidad pueden usarse en tejidos de diversa calidad en nuestro medio como ayuda en el diagnóstico de proliferaciones linfoides de difícil clasificación. Es importante hacerlas e interpretarlas de manera multidisciplinaria y considerar cada caso por separado.

Introduction: The European BIOMED-2 consortium was created to evaluate clonality in lymphoproliferations that are difficult to diagnose. In Colombia, the implementation of these tests began in 2015 at the Instituto Nacional de Cancerología E.S.E., Bogotá. Objectives: To determine the behavior of the rearrangement tests for lymphoid clonality and the difficulties of its implementation in our field through a series of retrospective and consecutive cases of lymphoid proliferation subjected to the BIOMED-2 protocols. Materials and methods: Clinical and histological data and the results of the rearrangement analysis of all cases of lymphoid proliferation subjected to the BIOMED-2 protocols between February 2015 and May 2019 were collected from clinical histories. Results: We recovered 132 samples from which 47 corresponded to reactive lymphoid hyperplasias, 62 to T lymphomas, 19 to B lymphomas, and three to lymphoid neoplasms of unestablished lineage. Only in one case did DNA extraction fail. According to these results, the greatest diagnostic difficulty for the pathologist was the analysis of T lymphoid infiltrates, most of which (44) were skin lesions. Conclusions: Clonality tests can be used in tissues of different quality to help in the diagnosis of lymphoid proliferations that are difficult to classify. It is important to implement and interpret them in an interdisciplinary way considering each case separately.

Overview of lymphoma diagnosis in Brazilian public health system patients: Open data analysis for health care planning

Abstract Introduction Knowing the information regarding the panorama of lymphoma diagnosis in patients treated in the Brazilian Public Unified Health System from the last 10 years is a challenge for Strategic Health Planning. Objective To characterize the Brazilian population with lymphoma treated in the Brazilian Public Unified Health System between 2008 and 2017 regarding staging, sex, residence site and mortality. Material and methods A descriptive, retrospective, and longitudinal trial with secondary data from DataSUS (SIA/SUS and SIM/SUS) obtained from patients with ICD-10 C81-85. Results There were 70,850 lymphoma cases between 2008 and 2017, of which 55% were male, the median age was 51 years, and 27% had Hodgkin Lymphoma. Most patients (56%) were treated outside the residence city. São Paulo State accounted for 25% of patients. Treatment initiation took more than 60 days in 27% of cases. A total of 45,601 deaths were due to lymphoma (12% Hodgkin Lymphoma and 88% Non-Hodgkin Lymphoma), with a median age 63 years, and were mainly males (55%). Staging data were inadequate in 23% of patients, and analysis was performed only on the valid records. Advanced disease was diagnosed in 58% of patients (60% male; 57% female) and was more common in Non-Hodgkin Lymphoma (62%) versus Hodgkin Lymphoma (49%). Discussion Late diagnosis interferes with mortality rates. Health promotion and cancer prevention campaigns, especially targeting the male public, and training for early diagnosis and early treatment are needed. Conclusion Effective measures for early diagnosis and treatment are urgently needed for lymphoma control.

The Prognostic Value of Prognostic Nutritional Index in Patients with Lymphoma--Review / 中国实验血液学杂志

The morbidity and mortality of hematological tumors have shown a rising tendency in recent years and become one of the major diseases which affect public health. The nutritional and inflammation status of the body has been proved to play an important role in the occurrence, development and prognosis of the blood system disease. The prognostic nutritional index (PNI) is an important index to reflect the nutritional and inflammation status of the body, and it can be calculated by serum albumin level and peripheral blood lymphocyte count. A large number of studies have reported that PNI can effectively predict the prognosis of several hematological tumors, including lymphoma. In this review, the prognostic value of PNI in patients with lymphoma was summarized briefly.

Pay attention to the detection and evaluation of CD30 in pathological diagnosis of lymphoma / 中华病理学杂志

CD30 is a transmembrane glycoprotein of tumor necrosis factor receptor family, which is expressed differently in various lymphomas. It has specific effects on the proliferation and function of tumor cells. However, the significance of CD30 expression has not been fully recognized by clinicians and pathologists, and the detection and evaluation of CD30 have not been standardized. The role of CD30 in the diagnosis of lymphoma, detection methods and reporting standards are summarized in the paper to improve the understanding of CD30.

Clinical analysis of 11 cases of lymphoma complicated with paraneoplastic neurological syndrome / 中华血液学杂志

Objective: To evaluate the clinical characteristics, treatment, and prognosis of patients with paraneoplastic neurological syndrome (PNS) associated with lymphoma. Methods: Between January 2012 and May 2021, the clinical data of 11 patients with lymphoma complicated with PNS treated at Peking Union Medical College Hospital were retrospectively reviewed. Results: Among the 11 patients (8 male and 3 female) , the median onset age was 61 (range, 33-78) years. The symptoms of PNS preceded lymphoma in 10 patients. The median time from the onset of PNS to the diagnosis of lymphoma was 4 months. Of the 11 patients, one had Hodgkin's lymphoma, 8 had B-cell non-Hodgkin's lymphoma, and 2 had peripheral T-cell lymphoma. Seven patients were evaluated for onconeural antibody, of whom 2 were positive (1 for anti-Ma2 antibody and 1 for anti-Yo antibody) . Of the 11 patients, the PNS symptoms of 3 patients were located in the central nervous system, 4 were located in the peripheral nervous system, and 3 were located in the muscle. Eight of the 11 patients were treated with glucocorticoid-based immunosuppressive therapy before the diagnosis of lymphoma. Patients with central nervous system involvement and dermatomyositis responded well to glucocorticoid, whereas patients with peripheral neuropathy did not significantly benefit. All 11 patients were treated with chemotherapy after the diagnosis of lymphoma. The efficacy of chemotherapy was assessed in 9 patients, 7 cases achieved complete remission, 1 case was evaluated as stable disease, and 1 case was evaluated as disease progression. The PNS symptoms of the patients who achieved complete response were almost completely recovered. The median follow-up time was 42 (range, 4-95) months. At the end of the follow-up period, 6 of the 11 patients survived, 3 were lost to follow-up, and 2 died. The median overall survival of the whole group was not reached. Conclusions: PNS can involve various parts of the nervous system and can be associated with different types of lymphoma. Through early diagnosis and treatment, the PNS symptoms could improve in most patients who achieve complete remission of lymphoma.

Functional investigation of chimeric antigen receptor T cells targeting LMP1 antigen / 中华血液学杂志

Objective: This study aimed to create a type of CAR-T cells that targets LMP1 antigen and study its immunotherapeutic effect on LMP1-positive hematological malignancies. Methods: To generate LMP1 CAR-T cells, a plasmid expressing LMP1 CAR was created using molecular cloning technology, and T cells were infected with LMP1 CAR lentivirus. The effects of LMP1 CAR-T cells on specific cytotoxicity against LMP1-positive tumor cell lines infected with the EB virus had been confirmed. Results: ① LMP1 protein expressing on EB virus-positive lymphoma cells surface was verified. ② The LMP1 CAR-expressing plasmid was created, and LMP1 CAR-T cells were obtained by infecting T cells with a lentivirus packaging system, with an infection efficiency of more than 80% . ③LMP1 CAR-T cells have a 4∶1 effect-to-target ratio in killing LMP1-positive lymphoma cells. The killing effect of LMP1 CAR-T cells on Raji cells was enhanced after 48 h of coculture, but there was no significant killing effect on Ramos, which are LMP1-negative lymphoma cells. ④After coculture with LMP1-positive lymphoma cells at a ratio of 1∶1 for 5 h, the degranulation effect was enhanced. The proportion of CD107a(+) T cells in the LMP1 CAR-T cell treatment group was significantly higher than that in the vector-T cell group [ (13.25±2.94) % vs (1.55±0.05) % , t=3.972, P=0.017]. ⑤After coculture with LMP1-positive lymphoma cells, the proportion of CD69(+) and CD25(+) T cells in the LMP1 CAR-T cell group was significantly higher than that in vector-T cell group [ (7.40±0.41) % vs (3.48±0.47) % , t=6.268, P=0.003; (73.00±4.73) % vs (57.67±2.60) % , t=2.842, P=0.047]. ⑥After coculture with LMP1-positive lymphoma cells, cytokine secretion in the LMP1 CAR-T cell group was higher than that in the vector-T cell group [interferon-gamma: (703±73) ng/L vs (422±87) ng/L, t=2.478, P=0.068; tumor necrosis factor-alpha: (215±35) ng/L vs (125±2) ng/L, t=2.536, P=0.064]. Conclusion: In this study, we found that the LMP1 protein is only found on the surface of the EBV-positive tumor cell. Simultaneously, we created an LMP1 CAR-expressing plasmid and obtained LMP1 CAR-T cells by infecting T cells with a lentivirus packaging system. Furthermore, we demonstrated that LMP1 CAR-T cells could specifically kill LMP1-positive tumor cells in vitro. The degranulation and activation effects of LMP1 CAR-T cells were enhanced after coculture with LMP1-positive tumor cells, indicating a potential clinical application.

CBL inhibits proliferation and invasion of breast cancer cells by ubiquitylation-mediated degradation of NCK2 / 南方医科大学学报

OBJECTIVE@#To observe the effects of Casitas B lymphoma (CBL) protein on proliferation, migration and invasion of breast cancer cells and explore its mechanism of action.@*METHODS@#Cultured breast cancer cell lines MDA-MB-231 and MCF7A were transfected with a CBL-overexpressing plasmid and a specific siRNA targeting CBL (siRNA-CBL), respectively, and the changes in cell proliferation, migration and invasion were examined using colony-forming assay, cell counting kit-8 (CCK-8), scratch test and Transwell assay. Flow cytometry and Western blotting were performed to examine the effects of CBL overexpression on cell cycle and epithelial-mesenchymal transition (EMT) of MDA-MB-231 cells, and the changes in the number of filamentous pseudopodia were observed by rhodamine- labeled phalloidin staining of the cytoskeleton. IP-mass spectrometry identified NCK2 as the interacting proteins of CBL, and their interaction was verified by immunoprecipitation and immunofluorescence co-localization experiments in HEK-293T cells transfected with the plasmids for overexpression of CBL, NCK2, or both. Cycloheximide tracking and ubiquitination assays were used for assessing the effects of CBL on stability and ubiquitination of NCK2 protein in MDA-MB-231 cells; CCK-8 and Transwell assays were used to determine the effect of NCK2 overexpression on CBL-mediated proliferation and migration of the cells.@*RESULTS@#The proliferation, migration and invasion were significantly suppressed in MDA-MB-231 cells overexpressing CBL (P < 0.05) and significantly enhanced in MCF7 cells with CBL silencing (P < 0.01). Silencing of CBL promoted G1/S transition in MCF7 cells (P < 0.05). Overexpression of CBL significantly decreased the expressions of CDK2/4 (P < 0.01), cyclinA2/B1/D1/D3/E2 (P < 0.05), Snail, N-cadherin, claudin-1 (P < 0.05), and upregulated the expression of E-cadherin (P < 0.05). CBL silencing upregulated the expressions of CDK2/4/6 (P < 0.05), cyclin A2/B1/D1/D3/E2 (P < 0.05), Snail, vimentin, and claudin-1 (P < 0.05) and down-regulated E-cadherin expression (P < 0.05). CBL overexpression obviously reduced the number of filamentous pseudopodia in MDA-MB-231 cells, and the reverse changes were observed in MCF7 cells with CBL silencing. In MDA-MB-231 cells, CBL overexpression lowered NCK2 protein stability (P < 0.05) and promoted its ubiquitin-mediated degradation (P < 0.01). Overexpression of NCK2 obviously reversed CBL-mediated inhibition of cell proliferation and migration (P < 0.01).@*CONCLUSION@#CBL can inhibit the proliferation, migration and invasion of breast cancer cells through ubiquitination-mediated degradation of NCK2.

The outcomes of Tiantan first-aid protocol on critically ill patients with primary central nervous system lymphoma / 中华外科杂志

Objective: To examine the outcomes of Tiantan first-aid protocol on critically ill patients with primary central nervous system lymphoma (PCNSL). Methods: The clinical data of 18 patients with PCNSL who were treated according to Tiantan first-aid protocol at Department of Neurosurgery,Beijing Tiantan Hospital, Capital Medical University from November 2019 to December 2021 were retrospectively analyzed. There were 9 males and 9 females, aged (56.9±11.1)years (range: 29 to 77 years). The median Karnofsky performance status(KPS) score at admission was 40 (range: 20 to 60). Three patients were mild coma, 3 were lethargy and 12 were conscious. The mean midline shift was 0.7 cm (range: 0 to 1.8 cm). After admission, all patients were treated according to the plan of rapid biopsy, rapid routine pathology and rapid salvage chemotherapy. The treatment procedures, clinical and radiographic outcomes, KPS score and adverse reactions of patients after chemotherapy were collected. Results: All of the 18 patients completed the first-aid treatment. The median duration from admission to the biopsy was 1 day (range: 0 to 5 days), from biopsy to routine pathological diagnosis was 1 day (range: 1 to 4 days) and from routine pathology to salvage chemotherapy was 1 day (range: 0 to 4 days). All the patients were pathologically confirmed with diffuse large B cell lymphoma, 1 patient was double-hit lymphoma. Seventeen patients underwent clinical remission and 1 died of cardiac dysfunction. The successful salvage rate was 17/18. Radiologically, complete remission was observed in 1 case, partial remission in 16 cases, and stable disease in 1 case. The median KPS score at discharge was 60 (range: 30 to 80). The mild gastrointestinal, hematological and hepatic adverse effects were observed after chemotherapy. Conclusion: Tiantan first-aid protocol is effective for critically ill patients with PCNSL, which has the merit to be popularly used and improved.

Evaluation of left ventricular function with left atrio-ventricular longitudinal strain in patients with lymphoma underwent anthracycline therapy / 中华心血管病杂志

Objective: To analyze the value of 3-dimensional speckle tracking echocardiograghy (3D-STE) derived strain parameters on the detection of subclinical myocardial deformation alterations in patients with lymphoma treated with anthracycline agents. Methods: This study was a retrospective study. A total of 37 patients with newly diagnosed diffuse large B cell non-Hodgkin lymphoma between December 2012 and December 2014 in Cancer Center, Fudan university were included. 3D-STE strain measurements were performed at baseline (T0),after the completion of two therapy circles (T1) and at the end of anthracycline regimen chemotherapy (Te). Echocardiography images were analyzed on the TTA workstation, and the indexes included left atrial minimum volume (LAVmin), left atrial emptying index (LAEF), left atrial active emptying index (LAAEF), as well as the left ventricular global longitudinal strain (LVGLS), left ventricular global circumferential strain (LVGCS), left atrial global longitudinal strain (LAGLS). The overall left atrioventricular longitudinal strain (LAVGLS) was calculated, which was the sum of the absolute values of LVGLS and LAGLS. The changes of left ventricular strain indexes measured by 3D-STE at different time points of patients were evaluated. Results: Thirty-seven patients with DLBCL, aged (48.3±12.1)years, including 23 males (63.9%), were enrolled. Compared with baseline, LVGLS (T1: (-18.63±4.73)% vs. (-22.13±4.40)%, P=0.001; Te:(-18.26±4.64)% vs. (-22.13±4.40)%, P<0.001), LAGLS (T1: (20.41±5.56)% vs. (23.98±5.59)%, P=0.003; Te: (17.60±3.96)% vs. (23.98±5.59)%, P<0.001) and LAVGLS (T1: (39.05±7.60)% vs. (46.11±7.77)%, P<0.001; Te: (40.34±8.55)% vs. (46.11±7.77)%, P<0.001) were all deteriorated at the T1 and Te. While LVGCS ((-21.98±5.82)% vs. (-26.15±7.51)%, P=0.010), LAVmin ((23.93±7.29)ml vs. (20.33±7.03)ml, P=0.029), LAEF ((28.94±11.16)% vs. (35.79±11.12)%, P=0.002) and LAAEF ((11.93±10.00)% vs. (18.10±9.96)%, P=0.013) were decreased only until Te. Conclusions: 3D-STE strain measurements could detect early myocaridial function alteration in patients receiving anthracycline regimen chemotherapy, thus may provide a novel approach to monitor anthracycline caused myocardial toxicity.

Analysis of Related Factors of Autologous Peripheral Hematopoietic Stem Cell Mobilization in Patients with Lymphoma and Myeloma / 中国实验血液学杂志

OBJECTIVE@#To explore the related factors affecting of autologous peripheral hematopoietic stem cell mobilization in patients with single center lymphoma and multiple myeloma.@*METHODS@#The clinical total of 30 patients with lymphoma or multiple myeloma who underwent autologous peripheral hematopoietic stem cell mobilization and transplantation in the Affiliated Hospital of Jiangsu University from March 2012 to December 2021 were retrospectively analyzed, including the patients' age, gender, disease type, chemotherapy course, mobilization scheme, collection times, CD34+ cell count, adverse events, days of neutrophil and platelet implantation after transplantation. The related factors affecting to the mobilization efficiency of peripheral blood stem cells was analyzed.@*RESULTS@#The mobilization scheme had a significant effect on the mobilization success rate of CD34+ cells. The mobilization success rate and optimal mobilization rate of intermediate-dose VP-16+G-CSF were higher than that of high-dose VP-16+G-CSF (P<0.05); the mobilization success rate of patients with previous chemotherapy courses ≤4 was higher than that of patients with chemotherapy courses >4 (100% vs 72.22%, P<0.05); the mobilization success rate of lymphoma patients was lower than that of myeloma patients (66.67% vs 94.44%, P<0.05); the mobilization success rate of lymphoma patients who received intermediate-dose VP-16+G-CSF was higher than that received high-dose VP-16+G-CSF patients (100% vs 42.86%, P<0.05). Patients' gender, age, time from diagnosis to mobilization and disease status had no significant effect on the efficiency of stem cell mobilization. Fifteen patients (50%) had febrile neutropenia during stem cell mobilization. There was no statistical difference in the incidence of febrile neutropenia between the two mobilization schemes (P>0.05); the incidence of severe thrombocytopenia in intermediate-dose VP-16+G-CSF group was higher than that in high-dose VP-16+G-CSF group (P<0.05). There was no statistical difference in the time of granulocyte implantation and platelet implantation after stem cell transplantation in patients with different mobilization schemes (P>0.05).@*CONCLUSION@#Mobilization regime, the number of previous chemotherapy course and disease type affect the mobilization efficiency of stem cells. Intermediate dose VP-16+G-CSF can improve the mobilization efficiency of stem cell in lymphoma patients, but should pay attention to the risk of bleeding.

Characteristics of Bone Marrow Cell Morphology and Immunophenotype in Patients with NHL Leukemia and Evaluation of NHL Bone Marrow Invasion / 中国实验血液学杂志

OBJECTIVE@#To observe the evaluation value of characteristics of bone marrow cell morphology and immunophenotype in patients with non-Hodgkin lymphoma (NHL) leukemia on the bone marrow invasion of NHL.@*METHODS@#The clinical data of 104 patients with NHL treated in the hospital from March 2016 to March 2021 were retrospectively analyzed, the characteristics of bone marrow smear morphology were recorded, and the analysis of bone marrow immunophenotype was performed, the evaluation value of bone marrow cell morphology and immunophenotype on NHL bone marrow invasion was analyzed.@*RESULTS@#One hundred and four patients with NHL leukemia were found to have increased lymphoma cells by examination of bone marrow cell morphology, including 57 cases of B-cell type, 39 cases of T-cell type and 8 cases of NK/T cell type. The characteristics of bone marrow cell morphology were as follows: the cell body was large, irregular or round like in shape, the cytoplasm was much and mostly stained blue, a few cells could see a few granules, the nucleus was round or round like, some were twisted, the chromatin was thick and nucleolus was different, of which the T-cell type lymphoma cells had strong heteromorphism and more obvious nucleolus. B-cell type mainly expressed CD19, HLA-DR and CD20, and the positive rate was ≥70%. T-cell type mainly expressed CD7, HLA-DR and CD38, and the positive rate was ≥40%. NK/T cell types mainly expressed CD56 and CD161, and the positive rates was ≥50%. Compared the proportion of lymphoma cells between bone marrow smear and immunophenotype examination, there was no statistical significant difference (P>0.05).@*CONCLUSION@#The characteristics of bone marrow cell morphology and immunophenotype have certain application value in the evaluation of bone marrow invasion in patients with NHL leukemia, both can complement each other and provide a feasible mean for the effective evaluation of bone marrow invasion in patients with NHL leukemia.

Clinical Study of Chemotherapy Combined with Antivirals for Adult T-cell Leukemia/Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To investigate the efficacy of chemotherapy combined with antivirals in adult T-cell leukemia/lymphoma (ATLL) patients and the prognostic factors.@*METHODS@#Forty nine patients with previously treated or treatment-nave ATLL from January 2018 to January 2021 were included in our study. The patients were divied into two groups according to whether they received antiviral treatment, twenty-seven patients were treated with chemotherapy combined with antivirals, including thirteen patients treated with recombinant interferon alpha-2b and CHOP therapy, eight patients treated with zidovudine combined with CHOP therapy, and 6 patients treated with CHOP regimen combined with interferon and zidovudine. Twenty-two patients were treated with CHOP therapy. The changes of symptom, hematological parameters, lactic dehydrogenase, β2-microglobulin, and the Ki-67 positive rate were compared between the two groups before and after treatments. The clinical efficacy of chemotherapy combined with antiviral therapy for ATLL was evaluated. The antiviral effect was assessed by detecting HTLV-1 virus copy number, and prognostic factors were analyzed.@*RESULTS@#The median follow-up time was 14 months. Compared with the patients treated with chemotherapy alone, the patients treated with chemotherapy combined with antivirals had lower tumor and virus loads, lower white blood cell count, lower lactate dehydrogenase level, lower β2-microglobulin lever, and lower Ki-67 positive rate (all P<0.05). The total effective rate of patients treated with chemotherapy combined with antivirals was significantly higher than those of patients treated with chemotherapy alone (63.0% vs 31.8%, P=0.035). The one-year overall survival (OS) rates of chemotherapy combined with antivirals groups and chemotherapy alone group were (74.1±2.9)％ and (40.9±2.1)％ (P=0.021), respectively. The one-year progress free survival (PFS) rates were (51.9±3.3)％ and (13.6±2.8)％ (P=0.017), respectively. Multivariable Cox regression analysis showed that HTLV-1 virus load (HR=7.518, 95%CI: 2.517-36.192, P=0.013) and antiviral therapy ［HR=5.617 (95%CI 1.803-11.293), P=0.027］ were independent prognostic factors for the long-term efficacy.@*CONCLUSION@#Addition of antivirals to chemotherapy can prolong PFS and OS in ATLL patients. HTLV-1 virus load and antiviral therapy are independent prognostic factors for ATLL patients.

Molecular Characteristics and Clinical Significance of IGH Gene Rearrangement in B-Cell Lymphoma--Review / 中国实验血液学杂志

B-cell lymphoma is the most common malignant lymphoma, and its incidence is increasing year by year. Some types are often indistinguishable from the reactive lesions through morphology combined with immunohistochemistry, so other auxiliary diagnostic methods are urgently needed. Since B-cell lymphoma is caused by malignant transformation of IGH rearranged B cells, the molecular characteristics of rearranged B cells can be used as an important reference for differentiating benign and malignant proliferations of lymphatic tissues. With the development of molecular biology technology, the detection of clonal rearrangement of IGH plays an important role in the diagnosis, efficacy evaluation and prognosis evaluation of lymphoma. This paper focuses on the molecular characteristics and clinical significance of clonal rearrangement of IGH in B-cell lymphoma.

Clinical Role of M Protein in Multiple Myeloma and Lymphoma --Review / 中国实验血液学杂志

M protein is often expressed in multiple myeloma and also can be detected in several lymphoma such as Waldenstrm macroglobulinaemia. M protein level can reflect the malignant degree and even genetic abnormality of multiple myeloma and lymphoma to some extent to predict the progress of the diseases, and the therapeutic response and prognosis of the disease can be evaluated by monitoring the M protein level and its change degree. This article reviews the role of M protein in the progression and prognosis of multiple myeloma and lymphoma, and discusses the differences in M protein expression between multiple myeloma and lymphoma, in order to provide new insights for clinical diagnosis, monitoring and evaluation of therapeutic effect.

Inhibitory Effect of Interference with PD-L1 Expression on B-cell lymphoma in Mice / 中国实验血液学杂志

OBJECTIVE@#To investigate the potential inhibitory effect of interference with PD-L1 on B cell lymphoma in mice.@*METHODS@#Three shRNA vectors for mouse CD274 (PD-L1) were constructed and transiently transfected into 293T cells. RT-qPCR was used to validate the interference efficiency of CD274. The shRNA vector that interfere efficiently with CD274 expression was packaged by using lentivirus packaging system to generate shRNA lentivirus, and then transfected into A20 lymphoma cell line. The methyl thiazol terazolium (MTT) assay was used to detect proliferation after 48 h culture of CD274-sh A20 cells. Meanwhile, BALB/c mice were hypodermically infected with CD274-sh A20 cells. Infected mice were observed daily and assessed to visualize tumor by in vivo fluorescence imaging.@*RESULTS@#The proliferation rate of CD274-sh A20 cells in vitro was significantly lower than that of A20 cells (P<0.05). The tumor size detected by in vivo fluorescence imaging showed a significant reduce in tumor bearing mice with CD274-sh compared with other tumor bearing mice. And the weight and size of tumor in CD274-sh group were also significantly reduced compared with other group (P<0.05). Moreover, the survival time of tumor bearing mice in CD274-sh group was longer than that of the PD-L1 high expression group.@*CONCLUSION@#PD-L1 plays an important role in the incidence and the progression of lymphoma, and the shRNA-based PD-L1 knockdown can inhibit cell proliferation of A20 cells and partly suppress tumor growth.