Supervivencia de pacientes con linfoma no-Hodgkin y síntomas neurológicos según inmunofenotipo del líquido cefalorraquídeo / Survival in non-Hodgkin´s lymphoma patients with neurological symptoms according to the cerebrospinal fluid immunophenotype

Introducción: Los linfomas no-Hodgkin pueden infiltrar el sistema nervioso central y producir síntomas neurológicos, lo cual incrementa la mortalidad. El diagnóstico de esta infiltración se puede realizar mediante el estudio del líquido cefalorraquídeo por la técnica de citometría de flujo, con una mayor sensibilidad que la citología convencional. Objetivo: Estimar la supervivencia global de pacientes con Linfoma no-Hodgkin y síntomas neurológicos según el inmunofenotipo celular del líquido cefalorraquídeo. Métodos: Se realizó un estudio analítico y prospectivo en 15 pacientes con diagnóstico confirmado de linfoma no-Hodgkin y síntomas neurológicos, con citología negativa del líquido cefalorraquídeo, tratados en el servicio de oncología del Instituto Nacional de Oncología y Radiobiología, durante los años 2017 y 2018. El inmunofenotipo fue caracterizado mediante citometría de flujo multiparamétrica. Resultados: El 60,0 por ciento de los pacientes fue del sexo femenino y el 53,4 por ciento mayor de 60 años. Hubo una mortalidad del 26,7 por ciento. Se realizaron 17 inmunofenotipos, el 58,9 por ciento fue normal, el 23,4 por ciento reactivo y el 17,7 por ciento sospechoso de malignidad. La supervivencia global fue mayor en pacientes con líquido cefalorraquídeo con inmunofenotipo normal (HR. 0.04). Conclusiones: La citometría de flujo pudo discriminar células sospechosas de malignidad, en pacientes cuyas citologías fueron negativas. La presencia en el líquido cefalorraquídeo de células atípicas, de pleocitosis y de un índice de linfocito-monocito alto se asoció con una supervivencia global menor(AU)

Introduction: When non-Hodgkin lymphomas infiltrate the central nervous system increases mortality. The diagnosis of this infiltration can be made by the study of cerebrospinal fluid using flow cytometry, with a higher sensitivity than conventional cytology. Objective: To estimate the relationship between the cellular immunophenotype of the cerebrospinal fluid and the overall survival of patients with non-Hodgkin lymphoma and neurological symptoms. Methods: An analytical and prospective study was conducted in 15 patients with confirmed diagnosis of non-Hodgkin lymphoma and neurological symptoms, with negative cytology of the cerebrospinal fluid. Patients cared at Oncology Department of the National Institute of Oncology and Radiobiology, during the years 2017-2018. The immunophenotype was characterized by multiparametric flow cytometry. Results: 60.0 percent of the patients was female and 53.4 percent older than 60 years. There was an overall mortality of 26.7 percent 17 immunophenotypes were found, 58.9 percent of them was normal, 23.4 percent reactive and 17.7 percent suspected of malignancy. Overall survival advantage was obtained in patients with cerebrospinal fluid with normal immunophenotype (HR 0.04). Conclusions: Flow cytometry could discriminate cells suspected of malignancy, in patients whose cytologies were negative. The presence in the cerebrospinal fluid of atypical cells, pleocytosis and a high lymphocyte-monocyte index were associated with a lower overall survival(AU)

Frequency, distribution, and immunomorphologic characteristics of peripheral T-cell lymphoma, not otherwise specified in a tertiary care center in Southern India

Aims: In world literature, Peripheral T-cell lymphomas (PTCLs) constituted about 12% of non-Hodgkin's lymphomas (NHL) of which PTCL not otherwise specified (NOS) was the most common subtype. This study was undertaken to ascertain the frequency and to assess the morphologic and immunophenotypic characteristics of PTCL, NOS over a period of 5 years in a tertiary care referral center in Southern India. Materials and Methods: Slides and blocks of all PTCL, NOS were retrieved, and a detailed morphologic and immunophenotypic study using a wide panel of antibodies was done. Results: During this study, NHL constitutes 77.61% of all lymphomas. PTCL formed about 12.55% (251 cases) of all NHL. PTCL NOS was the most common subtype (30.68%). The most common site of involvement was lymph nodes (75%) followed by extranodal sites such as soft tissue (8.33%), gastrointestinal tract including oral cavity (6.67%), nasal cavity (5%), central nervous system (1.67%), lung (1.67%), and spleen (1.67%). PTCL, NOS showed a broad morphologic spectrum and had varied morphologic patterns with some mimicking reactive hyperplasia and some mimicking known type of T-cell lymphomas, B-cell lymphomas, and Hodgkin's lymphoma. Conclusions: PTCL, NOS constituted about 30.68% of all PTCLs in our institution during a 5-year period and was the second most common type of PTCL. Immunophenotyping using a wide panel of T-cell antibodies is necessary to distinguish PTCL, NOS from other lymphomas which they mimic, as they are known to carry a worse prognosis.

Seguridad y efecto del uso compasivo del anticuerpo monoclonal anti-CD20 CIMABior® / Safety and response to treatment of compassionate use of an anti-CD20 monoclonal antibody CIMABior®

Introducción: el uso de anticuerpos monoclonales transformó el tratamiento de los linfomas no hodgkinianos. El Centro de Inmunología Molecular generó un anticuerpo anti-CD20 (CIMABior®) biosimilar del rituximab, que se ha caracterizado desde el punto de vista biológico, pero la seguridad y eficacia aún están en estudio. Objetivo: evaluar la seguridad y la respuesta al tratamiento con CIMABior ®, en pacientes con síndromes linfoproliferativos de células B tratados con intención compasiva. Métodos: estudio multicéntrico, exploratorio, con dos grupos de tratamiento (monoterapia o combinado con quimioterapia) no controlado, ni aleatorizado. Se incluyeron adultos con linfomas no hodgkinianos y leucemia linfocítica crónica, no elegibles para el ensayo clínico en ejecución con este producto. Se determinó la frecuencia de eventos adversos y se caracterizaron. La respuesta al tratamiento se definió como: remisión completa, remisión parcial, enfermedad estable o en progresión. Se calculó la tasa de respuesta objetiva (remisión completa más remisión parcial) con el intervalo de confianza al 95 por ciento, se evaluó la relación de algunas variables con la respuesta y se estimó la razón de Odss. Como medida de balance beneficio-riesgo se estimó el factor de Bayes. Resultados: los eventos adversos más frecuentes fueron: temblor (12,8 por ciento) y fiebre (10,3 por ciento). Los relacionados con el producto (43,4 por ciento) fueron leves o moderados y evolucionaron hacia la recuperación. No se informó muerte asociada directamente al tratamiento. Se constató respuesta objetiva global de 71,2 por ciento (59,6 por ciento de remisiones completas y 11,5 por ciento, parciales). La respuesta objetiva en el grupo de monoterapia fue de 66,7 por ciento y de 73,0 por ciento en el grupo de CIMABior® más quimioterapia, con remisiones completas de 46,7 por ciento y 64,9 por ciento, respectivamente. Conclusiones: el AcM CIMABior® es seguro, bien tolerado y se demostraron evidencias de efecto. El tratamiento aportó un beneficio clínico superior al riesgo de desarrollar algún evento adverso grave(AU)

Introduction : The use of monoclonal antibodies transformed the treatment of non-Hodgkin lymphomas. The Center of Molecular Immunology created an anti-CD20 monoclonal antibody (CIMABior®), biosimilar of rituximab, which has been characterized from a biological point of view, but the safety and effectiveness are still being studied. Objective: Evaluate the safety and response to treatment, in patients with B-cell malignancies with compassionate use of CIMABior®. Methods : A multicenter, exploratory, non-controlled, non-randomized study was conducted with two variants of treatments (monotherapy or combined with chemotherapy). Adults with non-Hodgkin lymphomas and chronic lymphocytic leukemia not eligible for clinical trial with this product were included. Frequency of adverse events was calculated and those were characterized. The response to treatment was defined as: complete response, partial response, stable disease or progressive disease. Overall response rate (complete plus partial remission) was calculated with 95 percent confidence interval. The relation of some variables with response was estimated per Odss ratio. As a measure of the benefit-risk balance, the Bayes factor was estimated. Results : The more frequent adverse events were: tremors (12.8 percent) and fever (10.3 percent). Those related to the product (43.4 percent) were minor and evolved to recovery. There were no deaths in reference to the treatment. An overall response of 71.2 percent was confirmed (59.6 percent complete remissions and 11.5 percent partial remission). The monotherapy group objective response was 66.7 percent and 73.0 percent in the CIMABior® plus chemotherapy group, with complete remissions of 46.7 percent and 64.9 percent respectively. Conclusions: The monoclonal antibodies CIMABor® is safe, well tolerated and evidences of its effectiveness was demonstrated. The treatment provided a superior clinical benefit to the risk of developing a severe adverse event(AU)

Nuclear morphometric study of Non-Hodgkin’s Lymphoma (NHL)

Background: Assessment of nuclear morphology is crucial for the diagnosis of non-Hodgkin's lymphoma. The non-Hodgkin’s lymphomas (NHL) constitute a heterogenous group of lymphoid neoplasms that vary in clinical behavior, histology, immunology and genetic profile. The diversity makes it difficult to diagnose accurately and reproducibly under light microscopy. The nuclear features play a major role in categorizing non-Hodgkin's lymphomas. Materials and methods: The present study was conducted for a period of two years in the Department of Oral Pathology, MNR dental College and Hospital, Sangareddy, Telangana, India. We encountered only three cases of Non-Hodgkin Lymphomas and so we have borrowed the some Sridhar Reddy Erugula, P. Sujatha, Ayesha Sameera, B. Suresh Reddy, Jesudass Govada, G. Sudhakar, Kandukuri Mahesh Kumar. Nuclear morphometric study of Non-Hodgkin's Lymphoma (NHL). IAIM, 2016; 3(5): 58-63. Page 59 specimens of NHL from other hospitals in Hyderabad, India. Hematoxylin and Eosin (H and E) stained histological sections were selected and assessed for nuclear area, perimeter and nuclear size of 40 nuclei of tumour cells were measured using the Windows® based image analysis software Results: Total number of cases in our study was 15. The mean nuclear area, perimeter and nuclear size of neoplastic cells were studied. In our study, the mean nuclear area, perimeter and nuclear size of neoplastic cells were significantly high in large cell lymphomas as compared to intermediate cells and small cell lymphoma. P value was significant. Conclusion: Our study supports the assumption that nuclear morphometry offers a more objective and reproducible diagnostic method for subcategorizing lymphoid tumors than is currently possible by conventional histopathological techniques.

Retrospective audit of clinico‑pathologic features and treatment outcomes in a cohort of elderly non‑Hodgkin’s lymphoma patients in a tertiary cancer center.

INTRODUCTION: There is limited data from India regarding elderly non‑Hodgkin’s lymphomas (NHL) patients. Hence, this audit was planned to study the clinic‑pathological features and treatment outcomes in elderly NHL patients. METHODS: Retrospective analysis of all NHL patients above age of 59 years treated at the author’s institute, between December 2010 and December 2013 was done. Case records were reviewed for baseline details, staging details, prognostic factors, treatment delivered, response, toxicity and efficacy. SPSS version 16 (IBM, Newyork) was used for analysis. Descriptive statistics was performed. Kaplan–Meir survival analysis was done for estimation of progression‑free survival (PFS) and overall survival (OS). Univariate analysis was done for identifying factors affecting PFS and OS. RESULTS: Out of 141 NHL patients, 67 patients were identified subjected to the inclusion criteria. The median age was 68 years (60–92). Majority were B‑cell NHL (86.6%). The commonest subtype in B‑cell was diffuse large B‑cell lymphoma (55.2%). Fifty‑four patients took treatment. The treatment intent was curative in 41 patients (61.2%). Among the patients receiving curative treatment, 16 patients couldn’t receive treatment in accordance with NCCN guidelines due to financial issues. Two years PFS was 55%. Two years PFS for B‑cell NHL and T‑cell NHL were 55% and 50% respectively (P = 0.982). Two years PFS for standard Rx and nonstandard Rx were 62% and 50% respectively, but it didn’t reach statistical significance (P = 0.537). Two years OS for the entire cohort was 84%. CONCLUSION: Standard treatment in accordance with guidelines can be delivered in elderly patients irrespective of age. There is a need for creating financial assistance for patients, so that potentially curative treatments are not denied.

O transplante de células-tronco hematopoéticas no tratamento dos linfomas não Hodgkin / Hematopoietic stem cell transplantation for non-Hodgkin lymphomas

No final da década de 70, ocorreu o primeiro relato de sucesso com a utilização de quimioterapia de alta dose, seguida de transplante de células-tronco hematopoéticas autólogo (TCTH auto), em pacientes com linfoma não Hodgkin (LNH). Desde então, o TCTH autólogo vem se constituindo em um importante instrumento na estratégia de tratamento dos LNH. Inúmeros estudos, em vários subtipos de linfomas, têm consolidado o papel do TCTH autólogo, principalmente como resgate em recidivas de doença. O melhor momento para a incorporação desta estratégia depende do subtipo do linfoma, do status de doença previamente ao transplante (sensível ou resistente) e de fatores clínico-biológicos associados à doença. Em recidiva sensível de linfoma difuso de grandes células, o TCTH autólogo é a terapia de escolha. Nestes pacientes, o transplante promove taxas de resposta completa em até 50 por cento dos casos, comparado a aproximadamente 15 por cento, quando esse resgate é realizado com protocolos quimioterápicos convencionais. O seu papel como parte da terapia de indução de remissão não está totalmente estabelecido. Em linfomas indolentes, principalmente folicular, é a terapia de escolha nas recidivas sensíveis à quimioterapia de resgate. Em linfomas de células do manto, o TCTH autólogo tem se incorporado à terapia de primeira linha, como consolidação de remissão. As indicações de TCTH alogênico em LNH têm se limitado aos casos de refratariedade ao tratamento convencional e recidiva pós-transplante autólogo, em pacientes jovens e sem comorbidades, em decorrência da alta toxicidade associada à utilização de regimes de condicionamento mieloablativos. A utilização de regimes de condicionamento de intensidade reduzida tem reduzido a toxicidade e ampliado o seu uso nos LNH recidivados ou refratários.

High-dose chemotherapy (HDT) followed by autologous bone marrow transplantation (ABMT) has proved to provide significant advantage regarding event-free and overall survival in patients with chemosensitive relapses of aggressive non-Hodgkin's lymphoma (NHL) after conventional therapy. These results encouraged many investigators to use HDT as part of first-line therapy but the results are contradictory. There is no consensus regarding management of relapsed or refractory DLBCL. In follicular lymphomas, autologous stem cell transplantation (SCT) is considered the treatment of choice for young patients with relapsed disease. Autologous SCT has also been evaluated in prospective trials as first-line treatment for high risk patients at diagnosis, but the results are not yet conclusive. In mantle cell lymphoma, autologous stem cell transplantation has been employed as part of first-line therapy. Allo-SCT for patients with lymphoma was first performed in the mid-1980s. The high transplant-related mortality, seen after myeloablative conditioning, discouraged broader interest in this approach and made further research difficult. The generally lower relapse rates after allo-SCT, the association of GvHD with reduced relapse rates, the increase of relapse rates after ex vivo or in vivo T-cell depletion, and the frequent responses to DLIs all support the existence of a graft-vs.-lymphoma effect. However, further data analysis supports the view that not all lymphomas are equal. While slowly proliferating diseases such as follicular lymphoma seem particularly sensitive targets for allogeneic T-cells, results of allo-SCT with aggressive B-cell lymphomas have been less convincing. Patients with these latter diseases obviously need vigorous debulking of their tumor prior to conditioning. Reduced-intensity conditioning fueled a renaissance of allo-SCT as treatment of lymphoma because the lower expected TRM was highly attractive for a patient population where...

Non-Hodgkin lymphomas recurrence in central nervous system

A retrospective study was carried out on 32 patients with non Hodgkin lymphomas (NHL) in order to evaluate incidence rate, outcome and risk factors of central nervous system (CNS) recurrence. The results showed that: 1 patient had general manifestation and local CNS symptoms, 3 patients had CNS recurrence later on. The cumulative risk of CNS recurrence in 4 years was 19%. The CNS recurrence risk was 39% in high grade NHL, occurring usually in the first 14months, 22% in moderate grade NHL, occurring usually in the first 6 years and 7% in low grade NHL with higher degree of malignancy. In multi value analysis, NHL with high and moderate grades were independent risk factors for CNS recurrence. There are no clear evidences about role of CNS prophylaxis in patients with moderate and high grade of NHL. The survival time is 1-2 months

Reproductive factors and risk of intermediate and high grade B-cell non-Hodgkin's lymphomas

To interview 60 female patients with intermediate and high grade B-cell non-Hodgkin's lymphomas (NHL), each patient was paired with a control who is a neighbour on the age factor. Females who use oral contraceptive pills have a high risk in intermediate and high grade B-cell non-Hodgkin's lymphomas compared to controls. Among the mothers, those using anti-lactating drugs have a lower risk of NHL compared to controls. Menopausal patients have a higher NHL risk compared to women in the reproductive years, whereas menopausal women on hormone replacement therapy have a lower risk compared to controls

Histopathological Studies of 300 Cases of Non-Hodgkin's Lymphoma in Korean Patients

Non-Hodgkin's malignant lymphoma is a relatively frequent lymphoreticular malignancy, and has been reported to constitute up to 5.2% of all malignant tumors in Korean patients. Various morphologic classifications of non-Hodgkin's lymphoma have been proposed, and among them, the Rappaport's classification has been most widely accepted. In 1982, a National Cancer Institute sponsored study on classification led to the creation of the Working Formulation in an attempt to resolve the controversy anddebate regarding the various classifications of non-Hodgkin's lymphoma. Angioimmunoblastic lymphadenopathy with dysproteinemia and polymorphic reticulosis are lymphoreticular proliferative disorders which have reported to transform to malignant lymphoma. The purpose of the present study is to reclassify non-Hodgkin's lymphomas according to the Working Formulation and to investigate the histopathological and immunocytochemical characteristics of angioimmunoblastic lymphadenopathy with dysproteinemia and polymorphic reticulosis. This study reviewed 300 cases of nodal and extranodal non-Hodgkin's lymphoma, 26 cases of polymorphic reticulosis, and 7 cases of angioimmunoblastic lymphadenopathy with dysproteinemia examined in the Departments of Pathology, Yonsei University College of Medicine, Youngdong Severance Hospital and Yonsei University Wonju College of Medicine from January 1977 to December 1986. In non-Hodgkin's lymphoma, each case was classified according to the Working Formulation and the Rappaport classification. All angioimmunoblastic lymphadenopathy with dysproteinemia and polymorphic reticulosis cases were subjected to histopathological analysis and a review of the clinical records. Immunocytochemical studies were done using kappa and lambda chains for B-cell markers and alpha-1-antichymotrypsin for histiocytic marker. The results obtained were as follows; 1) Among 300 cases of non-Hodgkin's lymphoma, the primarily involved tumor sites were the lymph nodes (141 cases), the gastrointestinal tract (67 cases), and the tonsils (32 cases) in descending order of frequency. 2) Using the Working Formulation, intermediategrade lymphomas occurred in 66.4% of the patients, and the most common subtype was "diffuse, large cell" (32.7%). By the Rappaport classification, 3 patients had nodular lymphomas, and "diffuse, histiocytic" was the most common subtype. 3) Infarction was present in 32 cases in which the "diffuse, lagre cell" type was most frequently associated. 4) In immunoperoxidase stains of 7 cases of angioimmunoblastic lymphadenopathy with dysproteinemia, proliferating immunoblasts revealed a polyclonal positivity for kappa and lambda chains. Atypical reticulocytes present in 26 cases of polymorphic reticulosis revealed a negativity for kappa, lambda and alpha-1-antichymotrypsin.

Histopathological Studies of 300 Cases of Non-Hodgkin's Lymphoma in Korean Patients

Non-Hodgkin's malignant lymphoma is a relatively frequent lymphoreticular malignancy, and has been reported to constitute up to 5.2% of all malignant tumors in Korean patients. Various morphologic classifications of non-Hodgkin's lymphoma have been proposed, and among them, the Rappaport's classification has been most widely accepted. In 1982, a National Cancer Institute sponsored study on classification led to the creation of the Working Formulation in an attempt to resolve the controversy anddebate regarding the various classifications of non-Hodgkin's lymphoma. Angioimmunoblastic lymphadenopathy with dysproteinemia and polymorphic reticulosis are lymphoreticular proliferative disorders which have reported to transform to malignant lymphoma. The purpose of the present study is to reclassify non-Hodgkin's lymphomas according to the Working Formulation and to investigate the histopathological and immunocytochemical characteristics of angioimmunoblastic lymphadenopathy with dysproteinemia and polymorphic reticulosis. This study reviewed 300 cases of nodal and extranodal non-Hodgkin's lymphoma, 26 cases of polymorphic reticulosis, and 7 cases of angioimmunoblastic lymphadenopathy with dysproteinemia examined in the Departments of Pathology, Yonsei University College of Medicine, Youngdong Severance Hospital and Yonsei University Wonju College of Medicine from January 1977 to December 1986. In non-Hodgkin's lymphoma, each case was classified according to the Working Formulation and the Rappaport classification. All angioimmunoblastic lymphadenopathy with dysproteinemia and polymorphic reticulosis cases were subjected to histopathological analysis and a review of the clinical records. Immunocytochemical studies were done using kappa and lambda chains for B-cell markers and alpha-1-antichymotrypsin for histiocytic marker. The results obtained were as follows; 1) Among 300 cases of non-Hodgkin's lymphoma, the primarily involved tumor sites were the lymph nodes (141 cases), the gastrointestinal tract (67 cases), and the tonsils (32 cases) in descending order of frequency. 2) Using the Working Formulation, intermediategrade lymphomas occurred in 66.4% of the patients, and the most common subtype was "diffuse, large cell" (32.7%). By the Rappaport classification, 3 patients had nodular lymphomas, and "diffuse, histiocytic" was the most common subtype. 3) Infarction was present in 32 cases in which the "diffuse, lagre cell" type was most frequently associated. 4) In immunoperoxidase stains of 7 cases of angioimmunoblastic lymphadenopathy with dysproteinemia, proliferating immunoblasts revealed a polyclonal positivity for kappa and lambda chains. Atypical reticulocytes present in 26 cases of polymorphic reticulosis revealed a negativity for kappa, lambda and alpha-1-antichymotrypsin.