Marginal zone lymphomas of the MALT type are a type of B-cell neoplasms that involve extranodal tissues and have an indolent clinical behavior. The stomach is the most common site and most patients ...are infected by Helicobacter pylori. An increase in the resistance of this bacterium to several antibiotics has been observed in the last years and this fact has determined the review of treatment guidelines. In areas with resistance to clarithromycin greater than 15%, classical triple therapy should be abandoned and quadruple regimens with or without bismuth are currently recommended. Thus, these new guidelines for eradication treatment should be applied to patients with gastric MALT lymphoma associated with H. pylori infection.
Los linfomas de la zona marginal de tipo MALT son un tipo de neoplasias de células B que afectan tejidos extraganglionares y tienen un curso clínico indolente. El estómago es la localización más frecuente y la mayor parte de los pacientes están infectados por Helicobacter pylori. En los últimos años se ha observado un aumento de la resistencia de esta bacteria a varios antibióticos y este hecho ha motivado la revisión de las pautas de tratamiento. Actualmente se propone que en zonas geográficas con resistencias a claritromicina superiores al 15% se abandone la triple terapia clásica y se utilicen pautas cuádruples con o sin bismuto. Así, estas nuevas recomendaciones sobre el tratamiento erradicador se deben aplicar a los pacientes con linfoma MALT gástrico asociado a infección por H. pylori.
Mucosa-associated lymphoid tissue (MALT) lymphomas are a diverse group of lymphoid neoplasms with B-cell origin, occurring in adult patients and usually having an indolent clinical behavior. These ...lymphomas may arise in different anatomic locations, sharing many clinicopathological characteristics, but also having substantial variances in the aetiology and genetic alterations. Chromosomal translocations are recurrent in MALT lymphomas with different prevalence among different sites, being the 4 most common: t(11;18)(q21;q21), t(1;14)(p22;q32), t(14;18)(q32;q21), and t(3;14)(p14.1;q32). Several chromosomal numerical abnormalities have also been described, but probably represent secondary genetic events. The mutational landscape of MALT lymphomas is wide, and the most frequent mutations are:
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, but many other genes may be involved. Similar to chromosomal translocations, certain mutations are enriched in specific lymphoma types. In the same line, variation in immunoglobulin gene usage is recognized among MALT lymphoma of different anatomic locations. In the last decade, several studies have analyzed the role of microRNA, transcriptomics and epigenetic alterations, further improving our knowledge about the pathogenic mechanisms in MALT lymphoma development. All these advances open the possibility of targeted directed treatment and push forward the concept of precision medicine in MALT lymphomas.
Treatment options for relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) are limited, with no standard of care; prognosis is poor, with 4- to 6-month median survival. Avadomide (CC-122) ...is a cereblon-modulating agent with immunomodulatory and direct antitumor activities. This phase 1 dose-expansion study assessed safety and clinical activity of avadomide monotherapy in patients with de novo R/R DLBCL and transformed lymphoma. Additionally, a novel gene expression classifier, which identifies tumors with a high immune cell infiltration, was shown to enrich for response to avadomide in R/R DLBCL. Ninety-seven patients with R/R DLBCL, including 12 patients with transformed lymphoma, received 3 to 5 mg avadomide administered on continuous or intermittent schedules until unacceptable toxicity, disease progression, or withdrawal. Eighty-two patients (85%) experienced ≥1 grade 3/4 treatment-emergent adverse events (AEs), most commonly neutropenia (51%), infections (24%), anemia (12%), and febrile neutropenia (10%). Discontinuations because of AEs occurred in 10% of patients. Introduction of an intermittent 5/7-day schedule improved tolerability and reduced frequency and severity of neutropenia, febrile neutropenia, and infections. Among 84 patients with de novo R/R DLBCL, overall response rate (ORR) was 29%, including 11% complete response (CR). Responses were cell-of-origin independent. Classifier-positive DLBCL patients (de novo) had an ORR of 44%, median progression-free survival (mPFS) of 6 months, and 16% CR vs an ORR of 19%, mPFS of 1.5 months, and 5% CR in classifier-negative patients (P = .0096). Avadomide is being evaluated in combination with other antilymphoma agents. This trial was registered at www.clinicaltrials.gov as #NCT01421524.
•Avadomide monotherapy is well tolerated and demonstrates preliminary clinical efficacy in the treatment of R/R DLBCL patients.•Avadomide monotherapy resulted in mPFS of 6 months in classifier-positive vs 1.5 months in classifier-negative R/R DLBCL patients.
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Summary
The study included 1848 diffuse large B‐cell lymphoma (DLBCL)patients treated with chemotherapy/rituximab. The aims were to validate the National Comprehensive Cancer Network International ...Prognostic Index (NCCN‐IPI) and explore the effect of adding high Beta‐2 microglobulin (β2M), primary extranodal presentation and intense treatment to the NCCN‐IPI variables in order to develop an improved index. Comparing survival curves, NCCN‐IPI discriminated better than IPI, separating four risk groups with 5‐year overall survival rates of 93%, 83%, 67% and 49%, but failing to identify a true high‐risk population. For the second aim the series was split into training and validation cohorts: in the former the multivariate model identified age, lactate dehydrogenase, Eastern Cooperative Oncology Group performance status, Stage III‐IV, and β2M as independently significant, whereas the NCCN‐IPI‐selected extranodal sites, primary extranodal presentation and intense treatments were not. These results were confirmed in the validation cohort. The Grupo Español de Linfomas/Trasplante de Médula ósea (GELTAMO)‐IPI developed here, with 7 points, significantly separated four risk groups (0, 1–3, 4 or ≥5 points) with 11%, 58%, 17% and 14% of patients, and 5‐year overall survival rates of 93%, 79%, 66% and 39%, respectively. In the comparison GELTAMO IPI discriminated better than the NCCN‐IPI. In conclusion, GELTAMO‐IPI is more accurate than the NCCN‐IPI and has statistical and practical advantages in that the better discrimination identifies an authentic high‐risk group and is not influenced by primary extranodal presentation or treatments of different intensity.
Objectives
To describe imaging and laboratory findings of confirmed PE diagnosed in COVID-19 patients and to evaluate the characteristics of COVID-19 patients with clinical PE suspicion. ...Characteristics of patients with COVID-19 and PE suspicion who required admission to the intensive care unit (ICU) were also analysed.
Methods
A retrospective study from March 18, 2020, until April 11, 2020. Inclusion criteria were patients with suspected PE and positive real-time reverse-transcription polymerase chain reaction (RT-PCR) for SARS-CoV-2. Exclusion criteria were negative or inconclusive RT-PCR and other chest CT indications. CTPA features were evaluated and severity scores, presence, and localisation of PE were reported.
d
-dimer and IL-6 determinations, ICU admission, and previous antithrombotic treatment were registered.
Results
Forty-seven PE suspicions with confirmed COVID-19 underwent CTPA. Sixteen patients were diagnosed with PE with a predominant segmental distribution. Statistically significant differences were found in the highest
d
-dimer determination in patients with PE and ICU admission regarding elevated IL-6 values.
Conclusion
PE in COVID-19 patients in our series might predominantly affect segmental arteries and the right lung. Results suggest that the higher the
d
-dimer concentration, the greater the likelihood of PE. Both assumptions should be assessed in future studies with a larger sample size.
Key Points
• On CT pulmonary angiography, pulmonary embolism in COVID-19 patients seems to be predominantly distributed in segmental arteries of the right lung, an assumption that needs to be approached in future research.
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Only the highest intraindividual determination of
d
-dimer from admission to CT scan seems to differentiate patients with pulmonary embolism from patients with a negative CTPA. However, interindividual variability calls for future studies to establish cut-off values in COVID-19 patients.
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Further studies with larger sample sizes are needed to determine whether the presence of PE could increase the risk of intensive care unit (ICU) admission in COVID-19 patients.
Marginal zone lymphomas of the MALT type are a type of B-cell neoplasms that involve extranodal tissues and have an indolent clinical behaviour. The stomach is the most common site and most patients ...are infected by Helicobacter pylori. An increase in the resistance of this bacterium to several antibiotics has been observed in the last years and this fact has determined the review of treatment guidelines. In areas with resistance to clarithromycin greater than 15%, classical triple therapy should be abandoned and quadruple regimens with or without bismuth are currently recommended. Thus, these new guidelines for eradication treatment should be applied to patients with gastric MALT lymphoma associated with H. pylori infection.
Here, we evaluate the sensitivity and specificity of a new 11-parameter flow cytometry (FCM) approach versus conventional cytology (CC) for detecting neoplastic cells in stabilized CSF samples from ...newly diagnosed aggressive B-cell non-Hodgkin's lymphoma (B-NHL) at high risk of CNS relapse, using a prospective, multicentric study design.
Moreover, we compared the distribution of different subpopulations of CSF leukocytes and the clinico-biologic characteristics of CSF+ versus CSF-, patients, in an attempt to define new algorithms useful for predicting CNS disease.
Overall, 27 (22%) of 123 patients showed infiltration by FCM, while CC was positive in only seven patients (6%), with three other cases being suspicious (2%). CC+/FCM+ samples typically had more than 20% neoplastic B cells and/or >or= one neoplastic B cell/microL, while FCM+/CC- samples showed lower levels (P < .0001) of infiltration. Interestingly, in Burkitt lymphoma, presence of CNS disease by FCM could be predicted with a high specificity when increased serum beta2-microglobulin and neurological symptoms coexisted, while peripheral blood involvement was the only independent parameter associated with CNS disease in diffuse large B-cell lymphoma, with low predictive value.
FCM significantly improves the sensitivity of CC for the identification of leptomeningeal disease in aggressive B-NHL at higher risk of CNS disease, particularly in paucicellular samples.
Real-world evidence comparing the efficacy of chimeric antigen receptor (CAR) T-cell therapy against that of the previous standard of care (SOC) for refractory large B-cell lymphoma (LBCL) is scarce. ...We retrospectively collected data from patients with LBCL according to SCHOLAR-1 criteria treated with commercial CAR T-cell therapy in Spain (204 patients included and 192 treated, 101 with axicabtagene ciloleucel axi-cel, and 91 with tisagenlecleucel tisa-cel) and compared the results with a historical refractory population of patients (n = 81) obtained from the GELTAMO-IPI study. We observed superior efficacy for CAR-T therapy (for both axi-cel and tisa-cel) over pSOC, with longer progression-free survival (PFS) (median of 5.6 vs. 4–6 months, p ≤ 0.001) and overall survival (OS) (median of 15 vs. 8 months, p < 0.001), independently of other prognostic factors (HR: 0.59 (95% CI: 0.44–0.80); p < 0.001 for PFS, and 0.45 (95% CI: 0.31–0.64) for OS). Within the CAR-T cohort, axi-cel showed longer PFS (median of 7.3 versus 2.8 months, respectively, p = 0.027) and OS (58% versus 42% at 12 months, respectively, p = 0.048) than tisa-cel. These differences were maintained in the multivariable analysis. On the other hand, axi-cel was independently associated with a higher risk of severe cytokine release syndrome and neurotoxicity. Our results suggest that the efficacy of CAR-T cell therapy is superior to pSOC in the real-world setting. Furthermore, axi-cel could be superior in efficacy to tisa-cel, although more toxic, in this group of refractory patients according to SCHOLAR-1 criteria.
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