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•Vaccination did not improve COVID-19 attributed mortality; still progression is milder with shorter hospitalization and ICU admission.•Use of monoclonal antibodies was effective in reducing attributable mortality.

Peripheral T-cell lymphoma (PTCL) is a clinically aggressive disease, with a poor response to therapy and a low overall survival rate of approximately 30% after 5 years. We have analyzed a series of 105 cases with a diagnosis of PTCL using a customized NanoString platform (NanoString Technologies, Seattle, WA) that includes 208 genes associated with T-cell differentiation, oncogenes and tumor suppressor genes, deregulated pathways, and stromal cell subpopulations. A comparative analysis of the various histological types of PTCL (angioimmunoblastic T-cell lymphoma [AITL]; PTCL with T follicular helper [TFH] phenotype; PTCL not otherwise specified [NOS]) showed that specific sets of genes were associated with each of the diagnoses. These included TFH markers, cytotoxic markers, and genes whose expression was a surrogate for specific cellular subpopulations, including follicular dendritic cells, mast cells, and genes belonging to precise survival (NF-κB) and other pathways. Furthermore, the mutational profile was analyzed using a custom panel that targeted 62 genes in 76 cases distributed in AITL, PTCL-TFH, and PTCL-NOS. The main differences among the 3 nodal PTCL classes involved the RHOAG17V mutations (P < .0001), which were approximately twice as frequent in AITL (34.09%) as in PTCL-TFH (16.66%) cases but were not detected in PTCL-NOS. A multivariate analysis identified gene sets that allowed the series of cases to be stratified into different risk groups. This study supports and validates the current division of PTCL into these 3 categories, identifies sets of markers that can be used for a more precise diagnosis, and recognizes the expression of B-cell genes as an IPI-independent prognostic factor for AITL.

•Allogeneic stem cell transplantation is the only curative option for most T cell neoplasias relapsing after autologous stem cell transplantation, demonstrated by a 2-year overall survival and progression-free survival of 66% and 58%, respectively.•The performance status of preallogeneic stem cell transplantation was the most relevant predictor of survival and progression-free survival in this study.•Patients who do not develop chronic graft-versus-host disease have an increased risk of relapse, and those who develop acute graft-versus-host disease have an increased nonrelapse mortality.•Our preliminary results showed similar overall survival and progression-free survival for haploidentical and unrelated donors. The use of post-transplant cyclophosphamide probably explains the reduced risk of acute graft-versus-host disease in the haploidentical group.

El incremento de la supervivencia del enfermo con cáncer, junto con el desarrollo de nuevas terapias antitumorales, han puesto de relieve el impacto negativo que las complicaciones vasculares asociadas con el tratamiento oncohematológico tienen en la salud cardiovascular del paciente con cáncer. El objetivo de este documento de consenso, promovido por el Grupo de Trabajo de Cardio-oncología de la Sociedad Española de Cardiología (SEC) y elaborado conjuntamente con diferentes áreas de conocimiento de la SEC junto con la Sociedad Española de Hematología y Hemoterapia (SEHH), la Sociedad Española de Oncología Médica (SEOM), la Sociedad Española de Oncología Radioterápica (SEOR), la Sociedad Española de Médicos Generales y de Familia (SEMG), la Asociación Española de Especialistas en Medicina del Trabajo (AEEMT), la Asociación Española de Enfermería Cardiovascular (AEEC), la Fundación Española del Corazón (FEC) y la Asociación Española contra el Cáncer (AECC), es proporcionar un enfoque coordinado, multidisciplinar y práctico para la estratificación, la monitorización y el tratamiento del riesgo cardiovascular de los pacientes con cáncer.

The spectrum of COVID-19 infection includes acute respiratory distress syndrome (ARDS) and macrophage activation syndrome (MAS), although the histological basis for these disorders has not been thoroughly explored. Post-mortem pulmonary and bone marrow biopsies were performed in 33 patients. Samples were studied with a combination of morphological and immunohistochemical techniques. Bone marrow studies were also performed in three living patients. Bone marrow post-mortem studies showed striking lesions of histiocytic hyperplasia with hemophagocytosis (HHH) in most (16/17) cases. This was also observed in three alive patients, where it mimicked the changes observed in hemophagocytic histiocytosis. Pulmonary changes included a combination of diffuse alveolar damage with fibrinous microthrombi predominantly involving small vessels, in particular the alveolar capillary. These findings were associated with the analytical and clinical symptoms, which helps us understand the respiratory insufficiency and reveal the histological substrate for the macrophage activation syndrome-like exhibited by these patients. Our results confirm that COVID-19 infection triggers a systemic immune-inflammatory disease and allow specific therapies to be proposed.

The spectrum of COVID-19 infection includes acute respiratory distress syndrome (ARDS) and macrophage activation syndrome (MAS), although the histological basis for these disorders has not been thoroughly explored. Post-mortem pulmonary and bone marrow biopsies were performed in 33 patients. Samples were studied with a combination of morphological and immunohistochemical techniques. Bone marrow studies were also performed in three living patients. Bone marrow post-mortem studies showed striking lesions of histiocytic hyperplasia with hemophagocytosis (HHH) in most (16/17) cases. This was also observed in three alive patients, where it mimicked the changes observed in hemophagocytic histiocytosis. Pulmonary changes included a combination of diffuse alveolar damage with fibrinous microthrombi predominantly involving small vessels, in particular the alveolar capillary. These findings were associated with the analytical and clinical symptoms, which helps us understand the respiratory insufficiency and reveal the histological substrate for the macrophage activation syndrome-like exhibited by these patients. Our results confirm that COVID-19 infection triggers a systemic immune-inflammatory disease and allow specific therapies to be proposed.

We are facing a pandemic that is going to affect a significant part of the population. At the end of April in the world there are about 3,000,000 cases, with 205,000 deaths and 860,000 patients recovered.

The presence of CD30+cells in cutaneous lymphomas has come to prominence in recent years as a potential diagnostic and therapeutic marker. In primary cutaneous marginal zone B-cell lymphomas, the presence of large CD30+cells with Hodgkin-like features and their significance have not yet been studied. Here we describe the main clinical, histologic, immunophenotypic, and molecular characteristics of 13 cases of primary cutaneous marginal zone lymphomas featuring >10% of CD30+large cells, and analyze their relationship with histologic and clinical progression of the disease and with other morphologic and immunophenotypic features. We report 10 male and 3 female patients, 4 with early-local disease and 8 with locoregional advanced disease without extracutaneous involvement but with a high relapse rate of 69%. We describe an association between a high level of CD30 expression and disease progression, with increased clinical recurrence in cases with >15% of CD30+cells. We also discuss the differential diagnosis with other cutaneous and systemic lymphomas, especially Hodgkin lymphoma.

El linfoma anaplásico de células grandes asociado a implantes mamarios (BIA-ALCL según sus siglas en inglés) es un tipo raro de linfoma no Hodgkin que se ha descrito en el contexto de la cirugía reconstructiva y estética de mama mediante implantes. Este segundo artículo presenta la parte del consenso de la Sociedad Española de Senología y Patología Mamaria (SESPM) sobre el tratamiento quirúrgico, médico, radioterápico, pronóstico y seguimiento.

El linfoma anaplásico de células grandes asociado a implantes mamarios (BIA-ALCL según sus siglas en inglés) es un tipo raro de linfoma no Hodgkin que se ha descrito en el contexto de la cirugía reconstructiva y estética de mama mediante implantes. Estos artículos presentan un consenso de la Sociedad Española de Senología y Patología Mamaria (SESPM) con la idea de unificar, en esta primera parte, los criterios de diagnóstico de esta enfermedad describiendo asimismo la epidemiología y la etiopatogenia.

We describe a series of 9 patients with Epstein-Barr virus (EBV)-positive mucocutaneous lymphoproliferative lesions that broadens the concept of EBV-positive mucocutaneous ulcer. We report 5 female and 4 male patients, with an average age of 74 years (range, 55 to 87 y), 2 of whom were HIV-positive. The lesions were located in the oropharynx, skin, and rectal and/or genital mucosa. Histopathologically, 6 cases showed a polymorphic pattern and 3 had a monomorphic and diffuse one, with angiotropism in 4 cases (2 each with the polymorphic and monomorphic patterns). Three of the cases expressed PDL1. In addition to its presence in the neoplastic lymphoid cells, EBV was also detected in adjacent epithelial cells in an oropharyngeal lesion. All cases responded to local therapy or adapted systemic chemotherapy in selected cases. This series extends the spectrum of this disorder to include some HIV-positive cases, patients with multiple lesions confined to a single anatomic area, lesions with an angiocentric pattern, and some cases with monomorphous large-cell cytology. We discuss the differential clinicopathologic diagnosis of this disorder and that of classic EBV large B-cell lymphoma.

The 2021 guidelines on the prevention of vascular disease (VD) in clinical practice published by the European Society of Cardiology (ESC) and supported by 13 other European scientific societies recognize the key role of screening for chronic kidney disease (CKD) in the prevention of VD. Vascular risk in CKD is categorized based on measurements of estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (ACR). Thus, moderate CKD is associated with a high vascular risk and severe CKD with a very high vascular risk requiring therapeutic action, and there is no need to apply other vascular risk scores when vascular risk is already very high due to CKD. Moreover, the ESC indicates that vascular risk assessment and the subsequent decision algorithm should start with measurement of eGFR and ACR. To optimize the implementation of the ESC 2021 guidelines on the prevention of CVD in Spain, we consider that: 1) Urine testing for albuminuria using ACR should be part of the clinical routine at the same level as blood glucose, cholesterolemia, and GFR estimation when these are used to make decisions on CVD risk. 2) Spanish public and private health services should have the necessary means and resources to optimally implement the ESC 2021 guidelines for the prevention of CVD in Spain, including ACR testing.

Las guías 2021 sobre la prevención de la enfermedad vascular (EV) en la práctica clínica publicadas por la European Society of Cardiology(ESC) y apoyadas por otras 13 Sociedades científicas europeas, reconocen el papel clave de la detección de la enfermedad renal crónica (ERC) en la prevención de la EV. El riesgo cardiovascular en la ERC se categoriza a partir de las medidas del filtrado glomerular estimado (FGe) y del cociente albúmina:creatinina en orina (ACRo). Así, la ERC moderada se asocia a un riesgo cardiovascular alto y la ERC grave a un riesgo cardiovascular muy alto, debiendo actuar en consecuencia desde el punto de vista terapéutico y no siendo necesario aplicar otras puntuaciones de riesgo vascular cuando este ya es muy alto debido a la ERC. Es más, la ESC sitúa la medida del FGe y del ACRo en el inicio de la estimación del riesgo cardiovascular y del algoritmo de decisión subsiguiente. A fin de optimizar la implementación de la guía 2021 de la ESC sobre la prevención de la EV en España, consideramos que: 1) El estudio de la orina para determinar la albuminuria mediante el ACRo debería formar parte de la rutina clínica al mismo nivel que las de la glucemia, la colesterolemia y la estimación del FG cuando estas se usan para tomar decisiones sobre el riesgo de EV. 2) Los servicios de salud públicos y privados españoles deberían disponer de los medios y recursos necesarios para implementar de forma óptima las Guías ESC 2021 de prevención de la EV en España, incluyendo la determinación del ACRo.

Peripheral T-cell lymphoma (PTCL) is a clinically aggressive disease, with a poor response to therapy and a low overall survival rate of around 30% after 5 years. We have analyzed a series of 105 cases with a diagnosis of PTCL using a customized NanoString platform that includes 208 genes associated with T-cell differentiation, oncogenes and tumor suppressor genes, deregulated pathways and stromal cell subpopulations. A comparative analysis of the various histological types of PTCL (angioimmunoblastic T-cell lymphoma, AITL; PTCL-with T follicular helper phenotype, PTCL-TFH; PTCL-not otherwise signified, PTCL-NOS) showed that specific sets of genes were associated with each of the diagnoses. These included TFH markers, cytotoxic markers and genes whose expression was a surrogate for specific cellular subpopulations, including follicular dendritic cells, mast cells and genes belonging to precise survival (NF-κB) and other pathways. Furthermore, the mutational profile was analyzed using a custom panel that targeted 62 genes in 76 cases distributed in AITL, PTCL-TFH and PTCL-NOS. The main differences between the three nodal PTCL classes involved the RHOAG17Vmutations (p<0.0001), which were approximately twice as frequent in AITL (34.09%) as in PTCL-TFH (16.66%) cases, but were not detected in PTCL-NOS. A multivariate analysis identified gene sets that allowed the series of cases to be stratified into different risk groups. This study supports and validates the current division of PTCL into these three categories, identifies sets of markers that can be used for a more precise diagnosis, and recognizes the expression of B-cell genes as an IPI-independent prognostic factor for AITL.

ABSTRACTIbrutinib has emerged as a promising therapy for patients with chronic lymphocytic leukemia (CLL) who are nonresponsive to standard therapies. The refractory state of monocytes and T-cell exhaustion in patients with CLL could explain the morbidity and mortality reported in these patients. We studied the effect of ibrutinib on the immune response of four relapsed patients with CLL during the first treatment cycle. We observed the ability to recover the standard response against bacterial stimulus in CD14+cells, improving levels of phospho-Erk1/2 and antigen presentation. Meanwhile, ibrutinib drove Th1-selective pressure in T lymphocytes, thus, reducing the PD-1 and PDL-1 expression. Our data suggest the impact of BTK inhibition along with immunomodulation on the innate immune response and a switch to the specific adaptive immune response, which might help to decrease infectious complications. The potential effect of ibrutinib on CLL patient outcomes is worthy of further study, because infections could be reduced with the use of ibrutinib.

NK/T-cell lymphomas are a group of clonal proliferations of NK- or, rarely, T-cell types and have peculiar clinicopathologic features. Most common site of involvement is the upper aerodigestive tract (nasal cavity, nasopharynx, paranasal sinuses, and palate). Association of autoimmune paraneoplastic disorders with NK/T-cell lymphomas is not well studied. Our patient was diagnosed with NK/T-cell lymphoma stage IV with skin involvement and treated frontline with CHOEP regimen. While he was under treatment, two immune complications presented: anterior uveitis of autoimmune origin refractory to steroids and myositis in lower limbs muscles. Autologous transplantation was rejected due to confirmed early relapse after first-line treatment, and the patient received second-line treatment according to the SMILE scheme, reaching complete response after four cycles. The patient underwent allogeneic transplantation and at the time of manuscript preparation is alive despite multiple complications. The disease should be suspected in patients with rhinitis or recurrent sinusitis, and early biopsy is recommended for all patients to avoid a delay in diagnosis. Our patient also presented symptoms of disease progression after first-line treatment, representing a paraneoplastic process, a very rare phenomenon in T-type lymphomas. This case is novel for the appearance of an inflammatory myositis, a histologically verified paraneoplastic phenomenon that responded to treatment for lymphoma.

López-Guillermo: Roche, Celgene, Mundipharma, Gilead, Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding. Dlouhi:Gilead: Equity Ownership. Martín García:Servier, Gilead: Consultancy. Sancho:CELLTRION, Inc.: Research Funding.

The development of the NCCN International Prognostic Index (NCCN-IPI) for patients with DLBCL treated in the rituximab era improves discrimination when compared to the original IPI model. The aim of the present study is to validate the results of the NCCN-IPI in a large independent series of patients in a different geographical area.

We have analyzed the results in terms of response rate and peripheral blood progenitor cell (PBPC) mobilization ability of two cisplatin-based chemotherapy salvage regimens [DHAP (cisplatin 100 mg/m2 iv day 1, ara-c 4 g/m2 iv day 2 and dexamethasone 40 mg po days 1-4) and ESHAP (etoposide 40 mg/m2 iv days 1–4, cisplatin 25 mg/m2 iv days 1–4, ara-c 2 g/m2 iv day 5 and methilprednisolone 500 mg iv days 1–5)] in a group of 110 patients with Hodgkin’s lymphoma (HL) in first or subsequent relapses. There were 70 males and 40 females with a median age at diagnosis of 29 years (range, 10 – 79). Sixty seven patients (64%) presented with advanced stage, 54% of them had B symptoms, 32% bulky mediastinal mass and 38%, extranodal disease. Disease status at the time of administration of the salvage protocol was primary refractory disease (PRD) (n = 16, 17%), first relapse (n = 65, 69%), second or subsequent relapse (n = 10, 11%) and relapse after a prior autologous stem cell transplantation (ASCT) (n = 3, 3%). Twenty-seven patients (26%) received the DHAP protocol and the remaining 78 (74%), the ESHAP protocol. Median time from diagnosis to the salvage therapy was 15 (range, 1 – 249) mo. In patients treated after a first relapse, the median duration of the first complete remission (CR) was 7 (range, 1 – 77) mo, with 18% of the patients relapsing after a long first CR (> 12 mo). Median number of cycles administered per patient was 2 (range, 1 – 3) with a median time interval between cycles of 28 (range, 21 – 76) days. PBPCs were collected after the second and the third cycle of chemotherapy in 35% and 49% of the patients respectively and was successful (> 2.0 x 106 CD34+ cells/kg) in 97% of them. Grade 3–4 hematological toxicity was seen in 20% of the cycles with severe neutropenia (< 0.5 x 109/l granulocytes) and thrombocytopenia (< 20 x 109/l platelets) developing in 26% and 7% of the cycles, respectively. The most frequent grade 3–4 extra-hematological toxicity was nausea/vomiting (30%). Procedure related mortality was 2%. Response rate (RR) was 78% [CR: 39%, partial remission (PR): 39%] with significant differences between patients treated for PRD [RR of 41% (CR: 12%, PR: 29%)] and those treated for disease relapse [RR of 86% (CR: 44%, PR: 42%)] (p = 0.005). Cisplatin-based regimens are a useful therapeutical strategy in the treatment of refractory or relapsed HL due to a high overall RR and an adequate PBPC mobilization ability. Results in terms of disease response are significantly worse in patients treated for PRD.

We have analyzed the results in terms of response rate and peripheral blood progenitor cell (PBPC) mobilization ability of two cisplatin-based chemotherapy salvage regimens [DHAP (cisplatin 100 mg/m2iv day 1, ara-c 4 g/m2iv day 2 and dexamethasone 40 mg po days 1-4) and ESHAP (etoposide 40 mg/m2iv days 1–4, cisplatin 25 mg/m2iv days 1–4, ara-c 2 g/m2iv day 5 and methilprednisolone 500 mg iv days 1–5)] in a group of 110 patients with Hodgkin's lymphoma (HL) in first or subsequent relapses. There were 70 males and 40 females with a median age at diagnosis of 29 years (range, 10 – 79). Sixty seven patients (64%) presented with advanced stage, 54% of them had B symptoms, 32% bulky mediastinal mass and 38%, extranodal disease. Disease status at the time of administration of the salvage protocol was primary refractory disease (PRD) (n = 16, 17%), first relapse (n = 65, 69%), second or subsequent relapse (n = 10, 11%) and relapse after a prior autologous stem cell transplantation (ASCT) (n = 3, 3%). Twenty-seven patients (26%) received the DHAP protocol and the remaining 78 (74%), the ESHAP protocol. Median time from diagnosis to the salvage therapy was 15 (range, 1 – 249) mo. In patients treated after a first relapse, the median duration of the first complete remission (CR) was 7 (range, 1 – 77) mo, with 18% of the patients relapsing after a long first CR (> 12 mo). Median number of cycles administered per patient was 2 (range, 1 – 3) with a median time interval between cycles of 28 (range, 21 – 76) days. PBPCs were collected after the second and the third cycle of chemotherapy in 35% and 49% of the patients respectively and was successful (> 2.0 x 106CD34+ cells/kg) in 97% of them. Grade 3–4 hematological toxicity was seen in 20% of the cycles with severe neutropenia (< 0.5 x 109/l granulocytes) and thrombocytopenia (< 20 x 109/l platelets) developing in 26% and 7% of the cycles, respectively. The most frequent grade 3–4 extra-hematological toxicity was nausea/vomiting (30%). Procedure related mortality was 2%. Response rate (RR) was 78% [CR: 39%, partial remission (PR): 39%] with significant differences between patients treated for PRD [RR of 41% (CR: 12%, PR: 29%)] and those treated for disease relapse [RR of 86% (CR: 44%, PR: 42%)] (p = 0.005). Cisplatin-based regimens are a useful therapeutical strategy in the treatment of refractory or relapsed HL due to a high overall RR and an adequate PBPC mobilization ability. Results in terms of disease response are significantly worse in patients treated for PRD.