Characteristics and impact factors of SARS-CoV-2 infection in adult patients with relapsed/refractory B-cell non-Hodgkin lymphoma receiving chimeric antigen receptor T-cell therapy / 中华血液学杂志

Objective: To explore the clinical characteristics and treatment of COVID-19 infection in patients with relapsed/refractory B-cell non-Hodgkin lymphoma before and after receiving chimeric antigen receptor T-cell therapy, and study the influencing factors of severe COVID-19 infection in these patients. Methods: The data of 59 patients with relapsed/refractory B-cell non-Hodgkin lymphoma who received chimeric antigen receptor T-cell therapy at the Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology and Department of Hematology, the Second Affiliated Hospital, College of Medicine, Zhejiang University between December 2017 and February 2023, and who were infected with novel coronavirus between December 2022 and February 2023 were retrospectively studied. Patients were divided into light, medium, severe, and critical groups, and the differences between the groups were analyzed using the chi-square test. A univariate logistic regression model was used to evaluate the contribution of each variable and its relationship with severe infection. The chi-square and Fisher's exact tests were used to analyze the differences between the B-cell aplasia and B-cell recovery (BCR) groups. Results: Of the 59 pre- and post-infusion infections, 39 (66.1%) led to mild COVID-19, 9 (15.3%) resulted in moderate COVID-19, 10 (16.9%) resulted in severe COVID-19, and 1 (1.7%) led to critical COVID-19. Moroever, age greater than 55 years, having received autologous hematopoietic stem cell transplantation, progressive disease status, and B-cell aplasia at the time of diagnosis of COVID-19 infection are factors affecting severe infection. Patients with B-cell aplasia had a more severe infection with COVID-19 (P<0.001), a longer duration (P=0.015), a longer antiviral therapy course (P<0.001), and a higher hospitalization rate (P<0.001) than the BCR group. Conclusion: Active prevention and treatment of COVID-19 infection remains a crucial issue requiring urgent attention in managing patients with relapsed/refractory B-cell non-Hodgkin lymphoma treated with chimeric antigen receptor T-cell therapy.

Splenic diffuse red-pulp small B-cell lymphoma associated with hepatitis B virus: a report of two cases / Linfoma esplênico difuso da polpa vermelha, de linfócitos B pequenos, associado ao vírus da hepatite B: relato de dois casos

ABSTRACT CONTEXT: Splenic diffuse red-pulp small B-cell lymphoma is a rare disease, representing less than 1% of all non-Hodgkin lymphomas (NHL). This entity is characterized by involvement of bone marrow sinusoids and peripheral blood. The majority of cases are at an advanced stage when diagnosed. Its pathogenesis is still poorly understood. CASE REPORTS: We report on two patients with chronic non-replicating hepatitis B virus (HBV) who developed splenic diffuse red-pulp small B-cell lymphoma. Both of them were in stage IV at diagnosis and evolved with aggressive disease. Both of them achieved a complete response through chemotherapy, but one of them died due to infectious complications during bone marrow transplantation. The other decided not to undergo transplantation and continues not to show any evidence of disease today (three years after treatment). Some studies have shown a possible association between B-cell NHL and HBV. Nonetheless, the mechanism through which this oncogenic virus interacts with B-cell NHL is still poorly understood. HBV is lymphotropic and may insert into the host's genome, thus causing overexpression of oncogenes and downregulation of tumor suppressor genes. Therefore, chronic stimulation by HBV can increase B-cell proliferation, which promotes monoclonal expansion of these cells and results in malignancy. CONCLUSION: HBV may be implicated in the pathogenesis of this lymphoma, although no direct association between these two entities could be proved in the present study. Further investigations are necessary.

RESUMO CONTEXTO: Linfoma esplênico difuso da polpa vermelha, de linfócitos B pequenos, é uma doença rara, representando menos do que 1% de todos os linfomas não Hodgkin. Essa entidade é caracterizada por envolvimento de sinusoides da medula óssea e sangue periférico. A maioria dos casos está em estádio avançado ao diagnóstico. Sua patogênese ainda é pouco compreendida. RELATOS DE CASOS: Reportamos dois pacientes com vírus da hepatite B (HBV) crônica não replicante que desenvolveram linfoma esplênico difuso da polpa vermelha, de linfócitos B pequenos. Ambos estavam em estádio IV ao diagnóstico e evoluíram com doença agressiva. Ambos alcançaram resposta completa com a quimioterapia, porém um deles evoluiu a óbito por intercorrências infecciosas durante o transplante de medula óssea e o outro optou por não realizar o transplante e encontra-se sem evidência de doença até os dias atuais (três anos após tratamento). Alguns estudos demonstraram a possível associação entre linfomas não Hodgkin B e HBV. Entretanto, o mecanismo pelo qual esse vírus oncogênico interage com linfoma não Hodgkin B ainda é pouco compreendido. HBV é linfotrópico e pode se inserir no genoma do receptor, causando superexpressão de oncogenes e downregulation de genes supressores tumorais. Portanto, o estímulo crônico pelo HBV pode aumentar a proliferação de células B, promovendo expansão monoclonal dessas células, resultando em malignidade. CONCLUSÃO: HBV pode estar implicado na patogênese desse linfoma, entretanto, uma associação direta entre essas duas entidades não pôde ser provada no presente estudo e investigações adicionais são necessárias.

Linfoma No-Hodgkin y pancreatitis aguda en gestante: reporte de caso / Non-Hodgkin's lymphoma and acute pancreatitis in pregnant women: case report

ANTECEDENTES: El linfoma no Hodgkin durante el embarazo es una entidad rara, el tipo difuso de células grandes es aún menos frecuente y se caracteriza por una alta tasa de progresión tumoral con poca expresión clínica. Su diagnóstico y tratamiento representan un reto clínico debido a la baja incidencia de la enfermedad y a las posibles repercusiones fetales a causa del tratamiento. CASO CLÍNICO: Gestante secundípara de 31 años que ingresa por cuadro de dolor abdominal y cifras elevadas de lactato deshidrogenasa. Durante la gestación precisa varios ingresos por pancreatitis aguda de repetición y cuadro de colestasis intrahepática. Tras el parto evoluciona tórpidamente con aparición de edema en esclavina en cuello y miembros superiores, siendo diagnosticada de gran masa torácica cuya biopsia es informada como Linfoma No Hodgkin tipo B difuso de células grandes primario mediastinal. Se administran dos ciclos de tratamiento quimioterápico tras lo cual remite completamente la enfermedad. Se induce el parto con prostaglandinas intravaginal, con recién nacido de 3350 gramos y APGAR 8/10. Tras un año la paciente permanece en remisión completa.

BACKGROUND: During pregnancy, Non-Hodgkin's lymphoma is a rare entity; the diffuse large cell lymphoma is still less common, and it has a high rate of tumor progression with a little clinical expression. Diagnosis and treatment is a huge challenge due to the low incidence of the condition and to the possible fetal effects because of the treatment. CLINICAL CASE: A 31-year-old woman -in her second delivery- was admitted with abdominal pain and elevated lactate dehydrogenase levels. During pregnancy, she was required several admissions reporting repeated acute pancreatitis and intrahepatic cholestasis. After delivery, it evolves into facial and upper extremity oedema, diagnosed with a large chest mass, resulting in the diagnosis of primary mediastinal large B-cell lymphoma through the biopsy. The disease goes into remission completely after two cycles of chemotherapy treatments are given. Labor is induced with intravaginal prostaglandins, with a newborn of 3350 g and Apgar 8/10. After a year, the patient remains in complete remission.

Cutaneous primary B-cell lymphomas: from diagnosis to treatment

AbstractPrimary cutaneous B-cell lymphomas are a heterogeneous group of mature B-cells neoplasms with tropism for the skin, whose biology and clinical course differ significantly from the equivalent nodal lymphomas. The most indolent forms comprise the primary cutaneous marginal zone and follicle center B-cell lymphomas that despite the excellent prognosis have cutaneous recurrences very commonly. The most aggressive forms include the primary cutaneous large B-cell lymphomas, consisting in two major groups: the leg type, with poor prognosis, and others, the latter representing a heterogeneous group of lymphomas from which specific entities are supposed to be individualized over time, such as intravascular large B-cell lymphomas. Treatment may include surgical excision, radiotherapy, antibiotics, corticosteroids, interferon, monoclonal antibodies and chemotherapy, depending on the type of lymphoma and on the type and location of the skin lesions. In subtypes with good prognosis is contraindicated overtreatment and in those associated with a worse prognosis the recommended therapy relies on CHOP-like regimens associated with rituximab, assisted or not with local radiotherapy. We review the primary cutaneous B-cell lymphomas, remembering the diagnostic criteria, differential diagnosis, classification, and prognostic factors and presenting the available therapies.

Targeting B-cell receptor signaling: Changing the treatment landscape of B-cell Lymphoma.

Introduced in 1998, the anti-CD20 monoclonal antibody rituximab, with its unique mechanism of action, was the first agent to improve survival in patients with B-cell lymphoma (BCL) treated with chemotherapy. Laboratory investigation of the B-cell receptor signaling pathway identified the critical nature of this pathway for normal B-cell development, survival and proliferation. Further investigation showed that lymphoma cell lines were also dependent upon this pathway and hence small molecule inhibitors of critical proteins in the pathway were synthesized and shown to be cytotoxic. Subsequent translation to the clinic has shown impressive activity in some types of B-cell lymphoma. The aim of this article is to provide an overview of the constituents of the BCR signaling pathway, to illustrate how addiction to this pathway is critical for survival of some BCL, and to summarize the clinical experience with novel small molecule inhibitors of specific proteins in the BCR pathway. We speculate that combination of these agents with newer drugs, each with a unique mechanism of action might lead to improved therapy and the eventual elimination of standard chemotherapy from our therapeutic arsenal.

Apport de l'immunohistochimie dans le diagnostic des lymphomes B agressifs chez les patients infectes ou non par le VIH en Republique democratique du Congo

Objectif. Determiner la contribution potentielle des techniques immunohistochimiques au diagnostic; et dans la prise en charge therapeutique des lymphomes-B agressifs chez des patients infectes ou non par le VIH; en R D Congo; dans le but de vulgarisation de cette approche; complementaire a l'etude morphologique; et indispensable pour le sous-typage de lymphomes; en particulier; de lymphomes-B agressifs. Methodes. Etude transversale et retrospective de 101 blocs de paraffine portant le diagnostic de lymphome et analyses entre 2005 et 2010; par des techniques morphologiques et immunohistochimiques; dans six laboratoires specialises de notre pays. Resultats. Les 81 blocs retenus; etaient tous CD20 positifs et CD3 negatifs; mais le profil etait variable pour d'autres marqueurs etudies. Le lymphome de Burkitt a ete identifie sur 40 blocs; incluant 7 sujets VIH+ (17;5); les lymphomes B diffus a grandes cellules; sur 35; avec 11; chez les VIH+ (31;4).Six lymphomes de forme intermediaire; dont 3; chez des sujets VIH+ (50). Conclusion. Cette etude a permis de classifier les lymphomes-B agressifs dans notre contexte; grace a l'immunohistochimie; justifiant le recours aux anticorps anti-CD20 pour leur traitement

Características clínicas y resultados terapéuticos de linfomas no Hodgkin de células grandes B mediastinal primarios / Clinical features and therapeutic results of primary mediastinal large B- cells non-Hodgkin's lymphomas

Se realizó un estudio observacional, descriptivo y retrospectivo para evaluar las características clinicobiológicas y los resultados terapéuticos del linfoma de células grandes B mediastinal primario, en 34 pacientes atendidos en el Hospital Clinicoquirúrgico Hermanos Ameijeiras desde junio de 1989 a febrero de 2009. Se halló predominio del sexo femenino (61,8 por ciento), edad promedio de 31,5 años (19 a 61 años) y de la raza blanca (70,6 por ciento). Fueron más frecuentes los estadios localizados (67,7 por ciento), sin síntomas B (64,7 por ciento) y con gran masa tumoral (70,6 por ciento). La supervivencia global y la supervivencia libre de progresión a los 5 años fueron 53,4 y 43,4 por ciento, respectivamente. La supervivencia global a los 3 años de los pacientes tratados con MACOPB/VACOPB, CHOP y R-CHOP fue de 77,7; 30,4 y 100 por ciento, respectivamente. Se comprobó que los pacientes tratados con MACOPB/VACOPB tuvieron mejores resultados que los tratados con CHOP. El índice pronóstico internacional ajustado a la edad no fue predictor de supervivencia. En el análisis multivariable, el único predictor de supervivencia fue el tratamiento utilizado (CHOP contra MACOPB). El uso rutinario de la radioterapia no tuvo impacto significativo en la supervivencia global ni en la supervivencia libre de progresión a los 5 años

A retrospective, descriptive and observational study was conducted to assess the clinical-biological features and the therapeutic results of the primary mediastinal of large B cells lymphoma in 34 patients seen in the Hermanos Ameijeiras Clinical Surgical Hospital from June, 1989 to February, 2009. There was predominance of female sex (61.8 percent), mean age of 31.5 years (19 to 61 years) and of white race (70.6 percent). The localized stages were more frequent (67.7 percent), without B symptoms (64.7 percent) and with a large tumor mass (70.6 percent). Global survival and the free of progression survival at five years were of 53.4 and 43.4 percent, respectively. The global survival at three years of the patients treated with MACOPB/VACOPB, CHOP and R-CHOP was of 77.7; 30.4 and 100 percent, respectively. It was proved that patients treated with MACOPB/VACOPB had better results than those treated with CHOP. Age-adjusted international prognostic rate was not a survival predictor. In multivariable analysis, the only survival predictor was the applied (CHOP versus MACOPB). The routine use of radiotherapy has neither a significant impact on the global survival nor on the free of progression survival at five years

Linfoma primario de tiroides: reporte de cuatro casos / Primary thyroid lymphoma: report of four cases

Primary thyroid lymphoma is uncommon and usually of non-Hodgkin type. We report four female patients with thyroid lymphoma. An 81 year-old patient that was operated and received three cycles of chemotherapy and was lost from follow up. A 16 year-old patient that is operated and received full chemotherapy and was discharged free of disease. A 80 year-old patient that was operated and died due to a multiple organ failure, 50 days after hospital admission and a 54 year-old female that was operated but rejected chemotherapy and was lost from follow up.

Linfoma do colo uterino: relato de dois casos e revisão da literatura / Lymphoma of the uterine cervix: report of two cases and review of the literature

A ocorrência de linfomas primários do trato genital feminino é rara. O diagnóstico normalmente não é possível pelo exame citológico, sendo necessária a biópsia do colo. Neste artigo, descrevemos duas pacientes encaminhadas ao nosso serviço por linfoma de colo uterino. Em uma delas, é claramente demonstrada a dificuldade diagnóstica que pode ocorrer nessa patologia. As duas pacientes foram tratadas com quimioterapia, apresentando evolução pós-operatória satisfatória. Não há um tratamento padrão para os linfomas de colo uterino. O tratamento local exclusivo é advogado por alguns estudos na literatura em estádio clínico IE, enquanto outros serviços optam pelo tratamento sistêmico em todos os estádios.

The occurrence of primary lymphomas of the female genital tract is rare. The diagnosis is usually not possible by the cytological examination; a tissue biopsy is necessary. The present paper reports two patients referred to our service with a diagnosis of cervical lymphoma. In one of them, the diagnostic difficulties are demonstrated. Both patients were submitted to chemotherapy with satisfactory post-operatory period. There is no standard treatment for uterine lymphomas. Exclusive local treatment is supported by some reports in the literature in clinical stage IE, while others prefer systemic treatment irrespective of clinical stage.

Thyroid primitive lymphoma on Hashimoto thyroiditis: about a case

Lymphoma is a rare form of malignant thyroid tumor. It often develops on concomitant or pre-existing thyroid disease. We present a case of thyroid lymphoma that developed on a Hashimoto thyroiditis and we review the clinical characteristics of the evolution of this disease as well as the controversy surrounding its management. Our patient was a 44 year old female that had surgery in our department because of a rapidly growing thyroid nodule associated with symptoms of cervical compression. Total thyroidectomy was performed. The pathology report concluded that it was a B cell lymphoma associated with Hashimoto thyroiditis. The treatment was completed by chemotherapy but the local evolution could not be stopped

Linfoma primario del sistema nervioso central en pacientes inmunocompetentes / Primary central nervous system lymphoma in immunocompetent patients

El linfoma primario del sistema nervioso central ha sido informado con frecuencia en pacientes que padecen síndromes de inmuno deficiencia. Sin embargo ésta no es una condición necesaria para su presentación, dado que existen informes de la enfermedad en sujetos inmunológicamente competentes. En el presente trabajo se analizaron en forma retrospectiva, los expedientes de 22 pacientes inmunocompetentes con diagnóstico confirmado de linfoma primario encefálico, se revisó la literatura mundial, con el fin de analizar objetivamente las manifestaciones clínicas, comportamiento radiológico, aspecto histopatológico, dificul tades diagnósticas y terapéuticas, así como las consideraciones pro nósticas. El promedio de edad fue de 65 años y con una relación equitativa hombre/mujer. El tiempo de evolución del cuadro clínico fue de 80.4 días y estuvo dominado por cefalea y déficit neurológico focal. En cuatro pacientes se encontraron lesiones múltiples, mientras que en el resto se trataba de lesiones únicas con localización predominante en la región periventricular de los hemisferios cerebrales. Todos los pacientes fueron manejados inicialmente con esteroides y sometidos a toma de biopsia por estereotaxia. La variedad histológica más frecuente fue la de células grandes difusas y la totalidad de los casos reaccionaron positivamente a antígenos de células B en la inmunohistoquímica. Los 22 pacientes fueron tratados con radio terapia y 10 de ellos además con quimioterapia con metotrexato. La supervivencia promedio fue de 11 meses en los pacientes radiados y de 36 meses en los que se agregó quimioterapia.

Primary central nervous system lymphoma has been traditionally described in patients with immunodeficiency syndromes; however, there is an increasing number of immunocompetent patients with this type of tumor that have been reported recently. In this paper we have retrospectively analyzed 22 immunocompetent patients with a confirmed diagnosis of primary lymphoma of the brain. The mean age in this group was 65 years with a similar male/female ratio. The time of evolution of the clinical course was 80.4 days and it was mainly characterized by headache and focal neurological deficit. In four patients multiple lesions were observed, while the remaining presented single lesions mainly located in the periventricular area of the cerebral hemispheres. All patients were initially administered steroids and a stereotactic biopsy was performed. The majority of tumors were histologically classified as diffuse large cells and all of them showed a positive reaction to B cells antigens on immunohistochemistry. All patients were treated with radiotherapy and in 10 of them, chemotherapy with methotrexate was also indicated. The mean survival rate was 11 months among patients treated with radiotherapy alone and increased to 36 months when chemotherapy was added.

Linfoma de celulas B tipo Malt de origen pielocalicial / B cell lymphoma, Malt type, of renal pelvis

Los procesos malignos de tipo linfomatosos que afectan el riñon son infrecuentes, y por lo general lo comprometen como una expresión más de una enfermedad sistémica. Clínicamente pueden ser asintomáticos y presentar hematuria e insuficiencia renal progresiva. El tratamiento es el de su enfermedad de base; en algunas situaciones está indicada la nefrectomía. Se presenta el caso de un paciente de 83 años de edad, en el estudio de rutina por prostatismo se detecta masa ocupante renal derecha. Con diagnóstico de tumor de vía excretora se realiza nefroureterectomía. El estudio anatomopatógico diferedo informa linfoma de células B tipo Malt (tumor linfoide asociado a mucosa), de origen pielocalicial con infiltración renal. Se realizan consideraciones anatomipatológicas, clínicas, diagnósticas y tertapéuticas de este tipo de linfoma, así como revisión de la bibliografía

T-cell rich B-cell lymphoma masquerading as Hodgkin disease: excellent outcome to inadequate therapy

T-cell rich B-cell lymphomas (TCRBCL) are characterized as non-Hodgkin lymphomas with a minor population of malignant B-cells scattered among predominant, reactive T-lymphocytes. This entity can easily be confused with lymphocyte-predominant Hodgkin disease (HD-LP), resulting in inappropriate therapy and a poor outcome. Because of their similarity, the pathology of patients treated for HD-LP with an inadequate or short-lived response to therapy should always be reviewed by an expert hematopathologist. We describe the first reported patient in Puerto Rico with TCRBCL, originally diagnosed and treated as HD-LP. Although the patient received partial, substandard therapy for TCRBCL, an excellent prolonged complete response ensued, thus, giving further credence to the fact that malignant lymphomas and TCRBCL in particular, are a protean group of disorders which should be precisely and accurately classified before the proper therapeutic strategies can be outlined

Primary lymphoma of the lung: a report of two cases.

Two cases of primary lung lymphoma B and T-cell type are reported. Their management with chemoradiotherapy is presented along with brief review of literature.