Phase I study of CBM.CD19 chimeric antigen receptor T cell in the treatment of refractory diffuse large B-cell lymphoma in Chinese patients / 医学前沿

Anti-CD19 chimeric antigen receptor (CAR) T cell therapy has shown impressive efficacy in treating B-cell malignancies. A single-center phase I dose-escalation study was conducted to evaluate the safety and efficacy of T cells transduced with CBM.CD19 CAR, a second-generation anti-CD19 CAR bearing 4-1BB costimulatory molecule, for the treatment of patients with refractory diffuse large B-cell lymphoma (DLBCL). Ten heavily treated patients with refractory DLBCL were given CBM.CD19 CAR-T cell (C-CAR011) treatment. The overall response rate was 20% and 50% at 4 and 12 weeks after the infusion of C-CAR011, respectively, and the disease control rate was 60% at 12 weeks after infusion. Treatment-emergent adverse events occurred in all patients. The incidence of cytokine release syndrome in all grades and grade ⩾ 3 was 90% and 0, respectively, which is consistent with the safety profile of axicabtagene ciloleucel and tisagenlecleucel. Neurotoxicity or other dose-limiting toxicities was not observed in any dose cohort of C-CAR011 therapy. Antitumor efficacy was apparent across dose cohorts. Therefore, C-CAR011 is a safe and effective therapeutic option for Chinese patients with refractory DLBCL, and further large-scale clinical trials are warranted.

Clinical Efficacy of Autologous Hematopoietic Stem Cell Transplantation for Patients with Diffuse Large B-Cell Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To compare the clinical efficacy of first-line and salvage autologous hematopoietic stem cell transplantation (auto-HSCT) in the treatment of patients with diffuse large B-cell lymphoma (DLBCL).@*METHODS@#The clinical data of 30 patients with DLBCL aged≤60 years old were retrospectively analyzed, and the patients were divided into first-line auto-HSCT group (15 cases) and salvage auto-HSCT group (refractory relapsed patients, 15 cases) according to the timing of transplantation, and the efficacy was analyzed. Anyone of the factors must be followed in patients receiving first-line HSCT: aaIPI score≥2 points, Ann-Arbor stage III-IV, large mass (diameter≥10 cm) or double expression of c-myc/BCL-2.@*RESULTS@#The median follow-up time for all patients after transplantation was 26 (3-103) months. Until the end of follow-up, 23 patients survived and 7 patients died. All the 7 dead patients with multiple organ failure due to the relapse and disease progression. The median survival time of 7 dead patients from transplantation to death was 6 (3-11) months. Among the 15 patients in the first-line auto-HSCT group, there were 2 patients relapsed (13.3%), 1 dead (6.7%), 14 patients survived [overall survival (OS) rate was 93.3%]. Among the 15 patients treated with salvage auto-HSCT, 6 patients died due to disease progression or relapse (40%), 9 cases survived (OS rate was 60%). There was a statistically significant difference in the mortality of patients between the two groups (6.7% vs 40%, P=0.006). The 3-year PFS and OS rates of patients in first-line auto-HSCT group were both 93.3%. The 3-year PFS and OS of patients in salvage auto-HSCT group were 58.7% and 59.2%. The 3-year OS and PFS of patients in the first-line auto-HSCT group were significantly higher than those in the salvage auto-HSCT group (P=0.03, P=0.04). The bone marrow suppression was the most common adverse complication and all patients showed grade III-IV granulocytopenia. Non-hematological adverse reactions were mainly gastrointestinal adverse reactions and oral mucositis. There was no statistically significant difference in adverse reactions between the two groups.@*CONCLUSION@#First-line auto-HSCT can be used as a consolidation treatment for DLBCL patients with poor prognostic factors. Auto-HSCT can further improve the prognosis of salvage chemotherapy-sensitive patients with refractory relapsed DLBCL.

Clinical characteristics of primary extranodal versus nodal diffuse large B-Cell Lymphoma: A retrospective cohort study in a cancer center

Background The outcome of patients with primary extranodal diffuse large B-cell lymphoma (PE-DLBCL) varies according to the primary site involved. Primary gastrointestinal, breast, bone, craniofacial, and testicular DLBCL are rare extranodal manifestations of DLBCL. Objective The objective of the study was to describe the clinical course of patients with PE-DLBCL disease in a referral cancer center. Results From 637 patients, 51 (8.77%) were considered as having PE-DLBCL (25 gastrointestinal, 12 craniofacial, 6 breast, 5 bone, and 3 with primary testicular DLBCL). Complete remission was higher in all PE-DLBCL sites (100% in testicular, 92.6% craniofacial, 83.3% breast, 80% bone, and 80% gastrointestinal) compared with 73.3% in nodal DLBCL. Although 2 cases with breast PE-DLBC relapsed, they achieved a complete response with chemotherapy. The overall survival at 5 years was 100%, 80%, 78%, 58%, 58%, and 62% for patients with primary breast, primary bone, gastrointestinal, primary craniofacial, primary testicular, and nodal DLBCL, respectively. Conclusions PE-DLBCLs constitute rare, primary sites of lymphoproliferative disorders in most cases, with localized disease and good prognosis. They require a combined chemoimmunotherapy with radiotherapy in most cases to improve local and systemic disease.

Síndromes linfoproliferativos gastrointestinales / Gastrointestinal lymphoproliferative syndrome

The gastrointestinal lymphoid system plays a relevant role. The daily and continuous interaction between gastrointestinal lymphocytes with food and intestinal microbes requires precise functioning. The pathologic spectrum of lymphocyte malfunction results in lymphomas. MALT lymphoma is the most frequently diagnosed lymphoma, but there are other lymphoproliferative diseases such as diffuse large B cell lymphoma, mantle cell lymphoma and T associated lymphoma. The gastroenterologist and the endoscopist need to know these diseases in detail to achieve early diagnosis and treatment.

El sistema linfoide de defensa abdominal tiene un relevante rol en el buen funcionamiento sistémico. La interacción diaria y continua con patógenos alimentarios y microbios comensales intestinales precisa un estrecho funcionamiento. Las alteraciones linfoides clonales favorecen el desarrollo de linfomas de diversos tipos. Si bien, el linfoma asociado a tejido linfoide de mucosas (MALT) es el más conocido en contexto de su asociación con Helicobacter pylori, el tracto gastrointestinal se puede ver afectado por otros linfomas como el linfoma difuso de células grandes B y linfomas indolentes como el linfoma folicular, el linfoma del manto y el linfoma T asociado a enteropatía. El gastroenterólogo y endoscopista precisan conocer en detalle estas entidades para un oportuno diagnóstico y adecuado tratamiento.

Linfoma primario difuso de células B grandes de mucosa gingival, en paciente VIH y EBV negativos / Primary gingival diffuse large b-cell lymphoma in HIV/EBR negative patient abstract

El linfoma difuso de células B grandes (LDCBG) es el linfoma más frecuente. La presentación clínica puede ser nodal o extranodal y sus síntomas dependen de la localización tumoral; en la mayoría de los casos están asociados a algún tipo de inmunodeficiencia. Referiremos un caso de LDCBG de presentación atípica en una localización muy infrecuente. Es importante tener en cuenta estas situaciones, ya que pueden simular otros procesos patológicos, retrasando así su correcto diagnóstico y por lo tanto un adecuado tratamiento. (AU)

Diffuse large cell lymphoma B (LDCBG) is the most common type of lymphoma. It´s clinical presentation can be nodal or extranodal and it's symptoms depend where the tumor is located and whether is associated or not with an immunodeficiency disease. We present an atypical presentation of a LDCBG in a very unusual location. It´s important to consider these kind of appearance, as they can mimic other oral pathological processes, delaying their correct diagnosis and therefore an appropriate treatment. (AU)

Guía de Práctica Clínica para la detección, tratamiento y seguimiento de Linfomas Hodgkin y No Hodgkin en población mayor de 18 años / Clinical practice guideline for the detection, treatment and follow-up of Hodgkin and Non-Hodgkin lymphomas in a population over 18 years of age

Esta guía esta dirigida al personal de la salud involucrado directamente en la atención de pacientes adultos mayores de 18 años con sospecha o diagnóstico de linfoma no Hodgkin B difuso de célula grande (Linfoma B difuso de células grandes), linfoma folicular (LF), linfoma de células del manto (LCM) y linfoma Hodgkin (LH), y a las instancias administrativas, empresas aseguradoras y entes gubernamentales involucrados en la generación de políticas en salud. Esta GPC basada en la evidencia incluye los temas de diagnóstico y tratamiento del Linfoma B difuso de células grandes, LF, LM y LH, bajo la perspectiva del Sistema General de Seguridad Social en Salud colombiano. Objetivos: Determinar los métodos diagnósticos más apropiados en pacientes con LBDCG para garantizar un diagnóstico preciso que permita una adecuada selección del tratamiento; Establecer las líneas de tratamiento en pacientes con LF para disminuir la heterogeneidad en la atención y mejorar los resultados del tratamiento; Determinar los esquemas de tratamiento de primera línea para pacientes con LCM en diferentes grupos de edad para disminuir la heterogeneidad y mejorar los resultados del mismo; y Mejorar la supervivencia libre de enfermedad y la supervivencia global de los pacientes adultos con LH.

Linfoma intravascular, un desafio diagnóstico: Caso clínico / Intravascular lymphoma: Report of one case

Intravascular lymphoma is a rare subtype of extranodal diffuse large B-cell lymphoma characterized by clonal proliferation of lymphocytes inside of small and medium caliber vessels. Its incidence is estimated at one case per million. The clinical picture is very variable, but frequently has skin and central nervous system involvement. It is diagnosed by demonstrating pathological blood vessel infiltration by lymphoma cells. We report a 44 years old male presenting with fever, malaise and erythematous lesions in the abdominal wall. An abdominal wall biopsy showed dilated vascular vessels with atypical cells in their lumen, compatible with large B-cell intravascular lymphoma. He was treated with rituximab, cyclophosphamide, adriamycin, vincristine and prednisone and an autologous hematopoietic stem cell transplantation, achieving a complete remission that has lasted two years.

Time-to-treatment of diffuse large B-cell lymphoma in São Paulo

OBJECTIVE: Diffuse large B-cell lymphoma is the most common type of non-Hodgkin lymphoma, accounting for nearly 50% of the cases in the Hematology Department of the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo and Instituto do Câncer do Estado de São Paulo. The treatment outcome is influenced by age, abnormal lactate dehydrogenase levels, extranodal infiltration, the disease stage and the patient's performance status. In this study, we sought to report the time-to-treatment of diffuse large B-cell lymphoma in São Paulo's public health system network and its impact on patient outcomes. METHODS: We prospectively followed a cohort of 42 consecutive patients with de novo diffuse large B-cell lymphoma between 2008 and 2012. RESULTS: Our patients had more advanced disease than that reported in the literature (61.9% vs. 46%). In São Paulo's public health system network, it took an average of 7.4 months for a diagnosis to be made and an additional 1.4 months to obtain an appointment with a specialist. Once at our Hematology Department, it took less than 20 days for staging, confirmation of the diagnosis and treatment initiation. An interval from signs or symptoms to treatment of more than 6 months was associated with inferior progression-free survival in 3 years (p = 0.049). CONCLUSION: A delay in the diagnosis of diffuse large B-cell lymphoma is a public health problem and may be associated with worse progression-free survival. .

Linfoma difuso de células B grandes tipo piernas de presentación facial / Diffuse large B-celllymphoma-Ieg type, facial presentation

El linfoma difuso de células B grandes es el subtipo más común de los linfomas no Hodking. La presentación clínico-patológica es heterogénea, los exámenes de inmunohistoquímica y moleculares genéticas son pieza clave en el diagnóstico. Entre las presentaciones cutáneas de este linfoma, la más común es la tipo piernas. Sin embargo, en el presente artículo se reporta un caso de una mujer con presentación facial y compromiso grave _ El diagnóstico definitivo se da por suma de criterios patológicos y por inmunohistoquímica. La paciente recibió esquema CHOP (ciclofosfamida, doxorrubicina, vincristina, prednisona), y en los dos primeros meses presentó una excelente respuesta.

Diffuse large B-cell lymphoma is the most common subtype of non-Hodgkin lymphomas. The clinical-pathological presentation is heterogeneous, immunohistochemistry and molecular genetics test are so important in diagnosis. Among the cutaneous presentations of this lymphoma, the most common is in the leg, however, on this occasion we reported a case of facial presentation with severe compromise. The definitive diagnosis is given by the sum of pathological and immunohistochemical criterias, the patient received CHOP scheme, which in the first two months had an excellent response.

Linfoma B difuso de células grandes en ovario: presentación de un caso / Diffuse large B-cell lymphoma of the ovary: a case report

El linfoma B difuso de células grandes es un linfoma no Hodgkin de fenotipo B y gran agresividad, con una diseminación a ovario del 7 por ciento. Su presentación de forma primaria en ovario es muy poco común, representando el 0,5 por ciento de todos los linfomas no Hodgkin y el 1,5 por ciento de todos los tumores de ovario. En este caso se presenta una paciente con clínica de dolor y distensión abdominal con una masa pélvica palpable, estableciéndose posteriormente el diagnóstico de linfoma B difuso de células grandes bilateral de ovario. En determinadas situaciones resulta complicado diferenciar el origen primario o secundario de la neoplasia. Los linfomas primarios localizados en ovario tienen un mejor pronóstico que los secundarios diseminados a ovario cuyo pronóstico es más sombrío. Sin embargo la mayoría de los casos publicados están basados en tratamiento quimioterápico previo a la era de rituximab.

The diffuse large B-cell lymphoma is a highly aggressive phenotype B non-Hodgkin lymphoma which is characterized by 7 percent dissemination in the ovary. Its presentation in primary form in the ovary is very uncommon and accounts for 0.5 percent of all lymphomas. In this case, the patient presents symptoms of pain and abdominal strain with a palpable pelvic mass and a post-diagnosis of bilateral diffuse large B-cell lymphoma in the ovary. In certain situations, it is complicated to differentiate between the primary and secondary origin of the neoplasia. The primary lymphomas located in the ovary have a better prognosis than secondary lymphomas whose prognosis is more uncertain. However, the majority of published cases are subjected to chemothe-rapeutic treatment prior to rituximab.

Primeros diez trasplantes autólogos de progenitores hematopoyéticos en adultos, en el servicio público de salud en Chile / First ten hematopoietic stem cell transplants performed in the adult public health service in Chile

Background: Hematopoietic stem cell transplantation (HSCT) is an effective therapy for hematological diseases such as lymphoma and multiple myeloma. In 2004, the Cancer Unit of the Ministry of Health incorporated the HSCT to the National Cancer Program in Adults. Until 2008 we purchased services to private institutions while implementing the national center for HSCT of adults in the Hospital del Salvador. Aim: To report the first ten HSCT conducted in this center. Material and Methods: All cases were approved by a national commission for adult HSCT. The entire process was carried out based on evidence-based protocols. Results: Six patients with Hodgkin lymphoma, three with multiple myeloma and one with a diffuse large B cell lymphoma were transplanted. Age range was 19 to 48 years and five patients were male. An average of 2.2 aphereses per patient was required. The CD 34 stem cell collection was 5.06 x 10(6) x Kg. The conditioning regimes were BEAM (carmus-tine, etoposide, cytosine arabinoside, melphalan) and melphalan 200 according to the underlying disease. Seventy percent of the patients developed mild to moderate mucositis and 50% had febrile neutropenia, with good response to treatment. In two cases there was an association with influenza. The engraftment of neutrophils and platelets was achieved on day +10 and +11 respectively. At follow-up until day +100, there was no morbidity or mortality. Conclusions: These results confirm the quality standard that this intervention has achieved in our institution. The Chilean National Center for HSCT on Adults should be established as a public core care, teaching and research facility.

Primary hepatic diffuse large B cell lymphoma: a case report

In this report we describe a rare case of primary hepatic diffuse large B cell lymphoma in a 67-year-old man who presented with abdominal pain, deteriorated liver function, elevated lactate dehydrogenase. He was found to have diffuse nodular intrahepatic space-occupying lesion with normal alpha-fetoprotein and carcino-embryogenic antigen. The final diagnosis was made by percutaneous biopsy of the liver as the clinical manifestation not consistent with common liver diseases. The patient was treated with R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone] without surgical resection with a favorable response. However, serious and complication was occurred after 4 cycles of chemotherapy, and the patient finally died of concurrent acute respiratory distress syndrome

Linfoma primario cutáneo difuso de células B grandes, tipo pierna (LPCDCBG-TP), localizado en cuero cabelludo / Diffuse primary large B-Cell cutaneous lymphoma

Los linfomas primarios cutáneos de células B se consideran actualmente como categoría distintiva de los linfomas primarios cutáneos y se reconocen subtipos característicos dentro de ellos. Se presenta un caso de linfoma primario cutáneo difuso de células B grandes, tipo pierna, con localización en el cuero cabelludo, donde se pudo disponer de estudios inmunohistoquímicos para su tipificación, que mostraron positividad para los marcadores CD20, bcl-2 y MUM-1, y negatividad para CD3 y bcl-6. Estos resultados, unidos a las características de las lesiones y el estudio histológico condujeron al diagnóstico final.

Linfoma gástrico primario / The conservative treatment with anthracycline containing chemotherapy has replaced gastrectomy as a standard approach against primary gastric lymphoma

El estómago constituye la localización más frecuente del linfoma no-Hodgkin extranodal. El linfoma difuso de células grandes B es el tipo histológico predominante. Es un linfoma agresivo que inicialmente se presenta como enfermedad localizada asociada o no a la infección con Helicobacter pylori. El tratamiento conservador con regímenes quimioterápicos con antraciclina seguidos o no por radioterapia en campos comprometidos ha reemplazado a la gastrectomía como tratamiento de primera línea.

The stomach is the extranodal site most commonly involved by non-Hodgkin lymphomas. Diffuse large B-cell lymphoma is the most common histotype category arising in this organ. This is an aggressive lymphoma usually presenting as limited disease, being associated or not to Helicobacter pylori infection. Conservative treatment with anthracycline-containing chemotherapy, followed or not by involved-field radiotherapy has replaced gastrectomy as standard approach against this malignancy.

Inusual presentación de un Linfoma B cutáneo en un paciente joven / Unusual presentation of a cutaneous B Lymphoma in a young male

Se reporta el caso de un paciente masculino de 23 años de edad, que se presenta con una úlcera de región latero cervical, única, sin compromiso del estado general. Se solicita estudio histopatológico de la lesión e inmunomarcación, con diagnóstico de Linfoma no Hodgkin B de células grandes cutáneos primarios. Se realiza una revisión sobre los Linfomas no Hodgkin B de células grandes cutáneos primarios, siendo anecdótica la presentación en pacientes jóvenes.

We report a case of a 23 year old male with a lateral cervical ulcer, without general involvement. Histophatological study and immunomarcation were positive to non Hodgkin Difuse Primary Cutaneous Large B-Cell Lymphoma. A revision was made about Primary Cutaneous B-Cell Lymphomas, being unusual this presentation in young people.