Front-line and second-line treatment for mantle cell lymphoma in clinical practice: A multicenter retrospective analysis.

BACKGROUND: There are few reports of clinical practice treatment patterns and efficacy in mantle cell lymphoma (MCL). MATERIALS AND METHODS: We retrospectively studied a large, multicenter, cohort of patients with MCL diagnosed between 2000 and 2020 in eight institutions. RESULTS: 536 patients were registered (73% male, median of 70 years). Front-line treatment was based on high-dose cytarabine, bendamustine, and anthracyclines in 42%, 12%, and 15%, respectively. The median PFS for all patients was 45 months; 68, 34, and 30 months for those who received high-dose cytarabine-based, bendamustine-based and anthracycline-based therapy. 204 patients received second-line. Bendamustine-based treatment was the most common second-line regimen (36% of patients). The median second-line PFS (sPFS) for the entire cohort was 14 months; 19, 24, and 31 for bendamustine-, platinum-, and high-dose cytarabine-based regimens, with broad confidence intervals for these latter estimates. Patients treated with cytarabine-based therapies in the front-line and those with front-line PFS longer than 24 months had a substantially superior sPFS. CONCLUSION: Front-line treatment in this cohort of MCL was as expected and with a median PFS of over 3.5 years. Second-line treatment strategies were heterogeneous and the median second-line PFS was little over 1 year.

Progression-free survival after front line, second line and third line in patients with follicular lymphoma treated in clinical practice.

BACKGROUND: The modern-day therapeutic landscape for follicular lymphoma (FL) includes a number of highly effective therapies. PATIENTS AND METHODS: We set out to determine progression-free survival (PFS) after front line, second line, and third line of therapy on the basis of relevant biological characteristics and therapeutic choices. Patients (n = 743, 51% females, median 60 years old) diagnosed with grade 1-2 FL between 1997 and 2016 in nine institutions were included. RESULTS: The median PFS1, PFS2, and PFS3 were 8.1 years (95% confidence interval [CI]: 7-9.3 years), 4.2 years (95% CI: 2.8-5.6 years) and 2.2 years (95% CI 1.7-2.8 years). We found longer PFS1 for (1) females, (2) younger age, (3) lower-risk follicular lymphoma international prognostic index (FLIPI), (4) standard intensity (over low intensity) regimens and (5) immunochemotherapy strategies and (6) maintenance rituximab. We found a shorter PFS2 for patients who received front-line immunochemotherapy. Older age at diagnosis correlated with a shorter PFS3. Intensity of front-line chemotherapy, maintenance, or POD24 status did not correlate with PFS2 or PFS3 in this dataset. INTERPRETATION: With current immunochemotherapy strategies, the natural course of FL is characterized by shorter-lasting remissions after each relapse. It will be interesting to see whether new therapies can alter this pattern.

Real-World Evidence of Relapsed/Refractory Mantle Cell Lymphoma Patients and Treatments: A Systematic Review.

Introduction: Mantle cell lymphoma (MCL) is an incurable disease with an aggressive clinical course, and most patients eventually relapse after chemotherapy. Targeted therapies developed for relapsed/refractory MCL have been approved based on clinical trial data. However, real-world setting data are scarce and scattered. Areas Covered: This systematic review aimed to collect, synthesize, and describe the characteristics and treatment outcomes of patients with relapsed/refractory MCL after receiving a second or subsequent line of therapy in the real-world setting. Expert Opinion: R/R MCL is clinically and biologically heterogeneous and still represents a therapeutic challenge, with high-risk and early relapsed patients remaining an unmet medical need. This systematic review is limited by the quality of the available data and the difficulty of comparing outcomes in R/R MCL due to the heterogeneity of the disease, but the results suggest that covalent BTKis should be positioned as second-line therapy, followed by CAR T-cells in BTK-i-relapsed patients. Chemo-free and combination therapies with established chemoimmunotherapy backbones in the relapsed and front-line settings have been recently developed, and front-line options are being improved to move targeted and cellular therapies to earlier lines, including front-line therapy, in elderly and younger fit patients. In the upcoming years, many new targeted agents will play an important role and will be incorporated to the routine practice as their sequence, and outcomes in unselected patients are determined.

Efficacy and safety of mRNA1273 SARS-CoV-2 vaccination in hematopoietic stem cell transplant recipients: Single center experience

Background: COVID-19 represents a worldwide pandemic and vaccination remains the most effective preventive strategy. Among hematological patients, COVID-19 has been associated with a high mortality rate. Vaccination against SARS-CoV-2 has shown high efficacy in reducing community transmission, hospitalization and deaths related to severe COVID-19 disease. However, patients with impaired immunity may have lower sero-responsiveness to vaccination.MethodsThis study focuses on hematopoietic stem cell transplantation (HSCT) recipients. We performed a unicenter, prospective, observational study of a cohort of 31 allogeneic and 56 autologous-HSCT recipients monitored between March 2021 and May 2021 for serological response after COVID-19 vaccination with two doses of mRNA1273 vaccine (Moderna). In order to determine seroconversion, serological status before vaccination was studied.ResultsAt a median range of 75 days after the second vaccine dose, seroconversion rates were 84% and 85% for the autologous and allogeneic-HSCT groups, respectively. We confirmed some potential risk factors for a negative serological response, such as receiving anti-CD20 therapy in the previous year before vaccination, a low B-lymphocyte count and hypogammaglobulinemia. Neutralizing antibodies were quantified in 44 patients, with a good correlation with serological tests. Adverse events were minimal.ConclusionmRNA1273 vaccination is safe and effective in HSCT recipients, especially in those presenting recovered immunity. (AU)

Introducción: Entre los pacientes hematológicos, la COVID-19 se ha asociado a una mayor mortalidad. La vacunación frente a SARS-CoV-2 es la principal estrategia de prevención y ha demostrado eficacia en la reducción de la transmisión, de la hospitalización y de la tasa de mortalidad. Aun así, los pacientes oncohematológicos con un sistema inmunológico disfuncional podrían presentar una respuesta menor a la vacunación.MétodosEstudio unicéntrico, prospectivo y observacional, con una cohorte de 31 receptores de un trasplante alogénico de progenitores hematopoyéticos y de 56 receptores de un trasplante autólogo que recibieron la vacunación frente a SARS-CoV-2 entre marzo de 2021 y mayo de 2021, con 2 dosis de la vacuna mRNA1273 (Moderna). Para poder determinar la tasa de seroconversión, se determinó el estado serológico previamente a la vacunación y posteriormente se monitorizó la respuesta serológica.ResultadosCon un tiempo medio de seguimiento de 75 días después de la segunda vacuna, la tasa de seroconversión fue del 84%, y del 85% en el grupo receptor de trasplante autólogo y alogénico, respectivamente. Se confirmaron algunos potenciales factores de riesgo para la ausencia de respuesta serológica, como haber recibido terapias anti-CD20, un recuento bajo de linfocitos B y la hipogammaglobulinemia. En 44 pacientes se cuantificaron títulos de anticuerpos neutralizantes, con buena correlación con los test serológicos. Los efectos adversos de la vacuna fueron mínimos.ConclusiónLa vacunación con mRNA1273 es segura y efectiva en los pacientes receptores de un trasplante de progenitores hematopoyéticos, especialmente en los que presentan reconstitución inmune previa. (AU)

Actualización en el diagnóstico, pronóstico y tratamiento del linfoma folicular / Follicular lymphoma: an update on diagnosis, prognosis, and management

El linfoma folicular, el linfoma indolente más frecuente, se origina en los linfocitos B del centro germinal del folículo linfoide y se caracteriza por la traslocación t(14;18). Clínicamente se manifiesta por la presencia de adenopatías, que pueden asociarse a síntomas constitucionales o citopenias. El diagnóstico se establece mediante la observación de una proliferación linfoide B de patrón nodular en la biopsia ganglionar, y la estadificación mediante una PET-TC y una biopsia de médula ósea. Una proporción significativa de pacientes no requiere tratamiento inmediato. Si lo requieren, suele estar basado en inmunoterapia anti-CD20 asociada o no a quimioterapia. A pesar de que la mayoría de los pacientes presentan una supervivencia global prolongada, las recaídas son muy frecuentes, y la recaída precoz y la transformación a un linfoma agresivo confieren un mucho peor pronóstico. Se encuentran en desarrollo nuevos tratamientos que cambiarán las perspectivas de estos pacientes en un futuro próximo. (AU)

Follicular lymphoma, the most common indolent lymphoma, originates from germinal centre B-cells of the lymphoid follicle, and is characterized by t(14;18). Clinical manifestations include the presence of lymphadenopathy, sometimes accompanied by constitutional symptoms or cytopenia. Diagnosis is established through the identification of a B-cell proliferation of nodular pattern in the lymph node biopsy. Upon staging with PET-CT and bone marrow biopsy, a significant proportion of patients do not need immediate treatment. When therapy is indicated, commonly used regimens include anti-CD20 immunotherapy with or without chemotherapy. Although overall survival for most patients is prolonged, relapses are very frequent, and early relapse and transformation to an aggressive lymphoma portend a much worse prognosis. New therapies are under development, which will most likely change outcomes for FL patients in the near future. (AU)

La revisión de 2016 de la clasificación de la OMS de las neoplasias linfoides: la visión del clínico / The 2016 revision of the WHO classification of lymphoid neoplasms: The clinician's view

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Importancia de la dosis de anticoagulantes orales directos / Importance of dosing direct oral anticoagulants appropriately

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Recomendaciones del Grupo Catalán de Trombosis (Tromboc@t Working Group) para el tratamiento de los pacientes que reciben anticoagulantes orales directos / Tromboc@t Working Group recommendations for management in patients receiving direct oral anticoagulants

Antecedentes y objetivos: En los últimos años los anticoagulantes orales directos (ACOD) se han convertido en una alternativa a los antagonistas de la vitamina K (AVK) para la prevención del ictus y embolia sistémica en pacientes con fibrilación auricular no valvular (FANV), así como para la prevención y tratamiento de la trombosis venosa profunda. Los ensayos clínicos han demostrado la no inferioridad y la potencial superioridad en comparación con la warfarina, lo cual permite ampliar las opciones de anticoagulación. En nuestro medio, las Unidades de Tratamiento Anticoagulante (UTA) y los Centros de Atención Primaria (CAP) son los encargados de la educación, seguimiento, control de adherencia y del manejo en situaciones especiales de los pacientes anticoagulados. Estas consideraciones han motivado la preparación del presente documento de consenso, que tiene como objetivo establecer recomendaciones que incorporen los hallazgos de la investigación científica a la práctica clínica para mejorar la calidad asistencial en el ámbito de la anticoagulación. Material y métodos: Un grupo de expertos del Grupo Catalán de Trombosis (TROMBOC@T) ha revisado la bibliografía publicada entre 2007 y 2016 para poder establecer recomendaciones basadas en la evidencia clínica. Resultados: Como resultado del proyecto se han establecido un conjunto de recomendaciones de carácter práctico que facilitarán el tratamiento, educación, seguimiento y manejo en situaciones especiales de los pacientes anticoagulados con ACOD. Conclusiones: El aumento progresivo del uso de los ACOD requiere establecer y homogeneizar las directrices de actuación clínica en el paciente anticoagulado con estos antitrombóticos tanto en las UTA como en los CAP

Background and objectives: In recent years, direct oral anticoagulants (DOACs) have become an alternative to vitamin K antagonists (VKA) for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF) as well as for prevention and treatment of deep venous thrombosis. Pivotal trials have demonstrated non-inferiority and potential superiority compared to warfarin, which increases the options of anticoagulant treatment. In our setting, the Anticoagulant Treatment Units (ATUs) and Primary Care Centres (PCCs) play an important role in the education, follow-up, adherence control and management in special situations of anticoagulated patients. These considerations have motivated us to elaborate the present consensus document that aims to establish clear recommendations that incorporate the findings of scientific research into clinical practice to improve the quality of care in the field of anticoagulation. Material and methods: A group of experts from the Catalan Thrombosis Group (TROMBOC@T) reviewed all published literature from 2009 to 2016, in order to provide recommendations based on clinical evidence. Results: As a result of the project, a set of practical recommendations have been established that will facilitate treatment, education, follow-up and management in special situations of anticoagulated patients with ACODs. Conclusions: Progressive increase in the use of DOACs calls for measures to establish and homogenise clinical management guidelines for patients anticoagulated with DOACs in ATUs and PCCs

Número de pacientes necesario a tratar con anticoagulantes orales directos con respecto a warfarina en la fibrilación auricular / Number needed to treat for direct oral anticoagulants over warfarin in atrial fibrillation

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Pronóstico similar de los linfomas transformados y los linfomas difusos de células B grandes de novo en pacientes tratados con inmunoquimioterapia / Similar prognosis of transformed and de novo diffuse large B-cell lymphomas in patients treated with immunochemotherapy

Antecedentes: El pronóstico de los linfomas difusos de células B grandes (LDCBG) transformados de linfomas indolentes (LT) ha sido considerado más desfavorable que el pronóstico de LDCBG de novo. Sin embargo, este parece haber mejorado desde la introducción de rituximab. Pacientes y métodos: Se compararon las características (incluyendo la célula de origen) y el pronóstico de 29 pacientes con LT y 101 con LDCBG de novo tratados con inmunoquimioterapia. Resultados: Los pacientes con LT y LDCBG de novo tenían características similares. Todos los casos de LT que evolucionaron de un linfoma folicular fueron linfomas de células B de tipo centro germinal, mientras que aquellos LT que evolucionaron de un linfoma de la zona marginal o leucemia linfocítica crónica fueron de tipo no centro germinal. El índice de respuesta completa fue similar en los LT y en los LDCBG de novo (62 frente a 66%, p = 0,825). Las probabilidades de supervivencia global y libre de progresión a 5 años (IC 95%) fueron del 59% (40-78) y el 41% (22-60) para LT y del 63% (53-73) y el 60% (50-70) para LDCBG de novo, respectivamente (p = 0,732 para supervivencia global y p = 0,169 para supervivencia libre de progresión). Conclusión: En este estudio, el pronóstico de los LT y LDCBG de novo tratados con inmunoquimioterapia fue similar. El papel de la intensificación con trasplante de precursores hematopoyéticos en el tratamiento del LT puede ser cuestionable en la era del rituximab (AU)

Background: The prognosis of diffuse large B-cell lymphomas (DLBCL) transformed from indolent lymphoma (TL) has been considered poorer than that of de novo DLBCL. However, it seems to have improved since the introduction of rituximab. Patients and methods: We compared the characteristics (including the cell-of-origin), and the prognosis of 29 patients with TL and 101 with de novo DLBCL treated with immunochemotherapy. Results: Patients with TL and de novo DLBCL had similar characteristics. All TL cases evolving from follicular lymphoma were germinal-center B-cell-like, while those TL from marginal zone lymphoma or chronic lymphocytic leukemia were non-germinal-center B-cell-like. The complete response rate was similar in TL and de novo DLBCL (62 vs. 66%, P = .825). The 5-year overall and progression-free survival probabilities (95% CI) were 59% (40-78) and 41% (22-60) for TL and 63% (53-73) and 60% (50-70) for de novo DLBCL, respectively (P = .732 for overall survival and P = .169 for progression-free survival). Conclusion: In this study, the prognosis of TL and de novo DLBCL treated with immunochemotherapy was similar. The role of intensification with stem cell transplantation in the management of TL may be questionable in the rituximab era (AU)

Linfoma de células del manto. Respuesta al tratamiento y pronóstico en 45 pacientes / Mantle cell lymphoma, response to treatment and prognosis in 45 patients

Fundamento y objetivo: El linfoma de células del manto (LCM) es un linfoma poco frecuente, con recaídas habituales y mal pronóstico. Este estudio analiza la respuesta al tratamiento y el pronóstico en una serie de pacientes con LCM. Pacientes y método: Estudio retrospectivo de los pacientes con LCM diagnosticados en un centro entre 1996 y 2013. Se dividió la cohorte en función del tratamiento recibido. Resultados: Se incluyeron 45 pacientes (32 varones) con una edad mediana de 66 años. Veintiún pacientes recibieron quimioterapia o quimioinmunoterapia intensiva (pautas con citarabina a dosis altas), 13 semiintensiva (sin citarabina a dosis altas), 8 no intensiva y 3 no precisaron tratamiento. La respuesta global fue del 85% con tratamiento intensivo y del 77% con semiintensivo. En el análisis multivariable el tratamiento intensivo se asoció a una mayor probabilidad de supervivencia libre de progresión (SLP) y supervivencia global (SG) (hazard ratio de 9,8 [IC 95% 2,7-35,5], p = 0,001 para la SLP y 4,5 [1,2-17,8], p = 0,03 para la SG). Conclusiones: En esta serie retrospectiva de pacientes con LCM el tratamiento intensivo se asoció a mejores resultados respecto al resto de las modalidades de tratamiento (AU)

Background and purpose Mantle cell lymphoma (MCL) is a rare lymphoproliferative disorder, with frequent relapses and a poor prognosis. This study analyzes response to treatment and prognosis in a series of MCL patients. Patients and method: Retrospective study of MCL patients diagnosed in a single institution between 1996 and 2013. The cohort was divided according to the treatment received. Results: Forty-five patients were included (32 male) with a median age of 66 years old. Twenty-one received intensive chemotherapy or chemoimmunotherapy (based on high-dose cytarabine), 13 semi-intensive (without high-dose cytarabine), 8 not intensive and 3 did not require treatment. Overall response rate was 85% in the intensive and 77% in the semi-intensive treatment groups. In multivariate analysis, intensive treatment was correlated with a longer progression-free survival (hazard ratio 9.8 [95% CI 2.7-35.5], P = .001) and overall survival (4.5 [1.2-17.8], P = .03). Conclusions: In this retrospective series of MCL patients, intensive treatment was correlated with better outcomes than the other treatment modalities (AU)

Anemia hemolítica autoinmunitaria refractaria a tratamiento médico tras ingesta de dióxido de clorina en un paciente con púrpura trombocitopénica inmunitaria / Autoimmune hemolytic anemia refractory to medical treatment after chlorine dioxide intake in a patient with idiopathic thrombocytopenic purpura

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Disminución de la respuesta eritropoyética en pacientes con anorexia nerviosa y anemia / Blunted erythropoietic response in the anemia of anorexia nervosa

Fundamento y objetivo: La causa o causas de la anemia que acompaña a la anorexia nerviosa (AN) no ha sido establecida, pero no parece relacionarse con deficiencias nutricionales ni cambios medulares. El objetivo de este trabajo fue evaluar la producción de eritropoyetina (EPO) en respuesta a la anemia en un pequeño grupo de pacientes con AN y anemia. Pacientes y métodos: Los niveles de EPO en muestras de suero de 41 mujeres con AN (11 con anemia y 30 sin alteraciones en los parámetros de la serie eritroide) se compararon con la respuesta observada en un grupo de pacientes de peso normal con anemia. Resultados: Las concentraciones de EPO en pacientes con AN anémicas fueron mayores que en las no anémicas: 20,63 mU/ml (4,04 a 28,46) frente a 8,7 mU/ml (3,9 a 20,93), p = 0,0088, pero el aumento de EPO fue menor de lo esperado (27,85 mU/ml [17,7 a 118,9]), p = 0,014. La correlación entre el IMC y la diferencia entre la EPO y la EPO esperada es inversa. Conclusiones: Una producción inadecuada de EPO puede explicar en parte la anemia en la AN. Son necesarios más estudios para investigar la causa de esta respuesta (AU)

Background and objective: The cause of the anemia in anorexia nervosa (AN) has not been fully ascertained. Ferritin, folate and cobalamin values are usually within normal ranges. Anemia does not have a relationship with bone marrow changes and erythropoietin (EPO) levels have not been investigated. The objective of this study was to evaluate the EPO response in a small group of AN patients. Patients and methods: EPO levels were measured in serum samples of 41 female AN patients (11 with anemia, and 30 with normal blood cell count). The adequacy of EPO response was assessed by comparing the increase observed in a group of normal weight patients with anemia. Results: EPO concentrations in anemic AN patients were higher than in non-anemic: 20.63 mU/mL (4.04-28.46) vs 8.7 mU/mL (3.9-20.93), P = .0088, but the increase in EPO was lower than expected (27.85 mU/mL [17.7-118.9]), P = .014. BMI and the difference between actual and expected EPO were inversely correlated. Conclusions: Inadequate EPO response may partly explain anemia in AN, but further studies are necessary (AU)