Mantle cell lymphoma (MCL) is considered a distinct type of B-cell lymphoma genetically characterized by the t(11;14) translocation and cyclin D1 overexpression. There is also a small subset of ...tumors negative for cyclin D1 expression that are morphologically and immunophenotypically indistinguishable from conventional MCL. Although in the last decades, the median overall survival of patients with MCL has improved significantly, it is still considered as one of the poorest prognoses diseases among B-cell lymphomas. Election of treatment for patients with MCL is complex due to the scarcity of solid evidence. Current available data shows that conventional chemotherapy does not yield satisfactory results as in other types of B-cell lymphomas. However, the role of other approaches such as autologous or allogenic stem cell transplantation, immunotherapy, the administration of consolidation or maintenance schedules, or the use of targeted therapies still lack clear indications. In view of this situation, the Spanish Group of Lymphomas/Autologous Bone Marrow Transplantation has conducted a series of reviews on different aspects of MCL, namely its diagnosis, prognosis, first-line and salvage treatment (both in young and elderly patients), new targeted therapies, and detection of minimal residual disease. On the basis of the available evidence, a series of recommendations have been issued with the intention of providing guidance to clinicians on the diagnosis, treatment, and monitoring of patients with MCL.
1 Complejo Hospitalario de Zamora
2 Hospital Marqués de Valdecilla, Santander
3 Hospital Duran i Reynals, LHospitalet de Llobregat
4 Hospital La Paz, Madrid
5 Hospital Juan Canalejo, La Coruña
6 ...Hospital Germans Trias i Pujol, Badalona
7 Hospital Dr. Peset, Valencia
8 Hospital del Mar, Barcelona
9 Hospital Clínico de Madrid
10 Hospital Universitario de Salamanca
11 Hospital Universitario de Getafe
12 Hospital Severo Ochoa, Leganés
13 Hospital General de Castellón
14 Hospital Virgen del Puerto, Plasencia
15 Hospital General de Jerez, Jerez de la Frontera
16 Hospital Carlos Haya, Málaga
17 Hospital Doce de Octubre, Madrid, Spain
Correspondence: Alejandro Martín, MD, PhD, Department of Hematology, Complejo Hospitalario de Zamora, Avenida de Requejo 35, Zamora 49022, Spain. E-mail: amartingar{at}aehh.org
Background: The role of re-treatment with rituximab in aggressive B-cell lymphomas still needs to be defined. This study evaluated the influence of prior exposure to rituximab on response rates and survival in patients with diffuse large B-cell lymphoma treated with rituximab plus etoposide, cytarabine, cisplatinum and methylprednisolone (R-ESHAP).
Design and Methods: We retrospectively analyzed 163 patients with relapsed or refractory diffuse large B-cell lymphoma who received R-ESHAP as salvage therapy with a curative purpose. Patients were divided into two groups according to whether rituximab had been administered (n=94, "R+" group) or not (n=69, "R-" group) prior to R-ESHAP.
Results: Response rates were significantly higher in the R- group in the univariate but not in the multivariate analysis. In the analysis restricted to the R+ group, we observed very low complete remission and overall response rates in patients with primary refractory disease (8% and 33%, respectively), as compared to those in patients who were in first partial remission (41% and 86%) or who had relapsed disease (50% and 75%) ( p <0.01 in both cases). Overall, 60% and 65% of patients in the R+ and R- groups, respectively, underwent stem-cell transplantation after the salvage therapy. With a median follow-up of 29 months (range, 6–84), patients in the R+ group had significantly worse progression-free survival (17% vs. 57% at 3 years, p <0.0001) and overall survival (38% v 67% at 3 years, p =0.0005) than patients in the R- group. Prior exposure to rituximab was also an independent adverse prognostic factor for both progression-free survival (RR: 2.0; 95% CI: 1.2–3.3, p =0.008) and overall survival (RR: 2.2; 95% CI: 1.3–3.9, p =0.004).
Conclusions: R-ESHAP was associated with a high response rate in patients who were not refractory to upfront rituximab-based chemotherapy. However, the survival outcome was poor for patients previously exposed to rituximab, as compared to in those who had not previously been treated with rituximab.
Key words: R-ESHAP, salvage therapy, diffuse large B-cell lymphoma, rituximab.
Los mastocitos cutáneos y subcutáneos son neoplasias compuestas por mastocitos que forman parte de la piel en los caninos. Es un tumor muy común y el tratamiento va enfocado a la agresividad que ...pudiera presentar. Ocasionalmente se puede administrar un tratamiento local, sin embargo, este no debe considerarse en pacientes con metástasis. La estadificac ión del tumor es de gran importancia para dar un diagnóstico, tratamiento y pronóstico para aquellos pacientes afectados por esta patología. En este trabajo se presenta el caso clínico de un canino Pastor Alemán de 11 años con la presencia de una estructura ulcerada en el pabellón auricular derecho. Se realizó diagnóstico por citología e histopatológico de mastocitoma canino grado II y baja malignidad de acuerdo con la clasificación de Pakiel. Al paciente se le realizó una resección parcial del pabellón auricular con presencia de bordes limpios en los resultados del estudio histopatológico. El objetivo de este trabajo es reportar un caso clínico con la presencia de mastocitoma en el pabellón auricular en un perro doméstico.
Background
Consensus is lacking regarding the optimal salvage therapy for patients with follicular lymphoma who relapse after or are refractory to immunochemotherapy.
Methods
This phase II trial ...evaluated the efficacy and safety of response‐adapted therapy with rituximab, bendamustine, mitoxantrone, and dexamethasone (RBMD) in follicular lymphoma patients who relapsed after or were refractory to first‐line immunochemotherapy. Sixty patients received three treatment cycles, and depending on their response received an additional one (complete/unconfirmed complete response) or three (partial response) cycles. Patients who responded to induction received rituximab maintenance therapy for 2 years.
Results
Thirty‐three (55%) and 42 (70%) patients achieved complete/unconfirmed complete response after three cycles and on completing induction therapy (4‐6 cycles), respectively (final overall response rate, 88.3%). Median progression‐free survival was 56.4 months (median follow‐up, 28.3 months; 95% CI, 15.6‐51.2). Overall survival was not reached. Progression‐free survival did not differ between patients who received four vs six cycles (P = .6665), nor between patients who did/did not receive rituximab maintenance after first‐line therapy (P = .5790). Median progression‐free survival in the 10 refractory patients was 25.5 months (95% CI, 0.6‐N/A) and was longer in patients who had shown progression of disease after 24 months of first‐line therapy (median, 56.4 months; 95% CI, 19.8‐56.4) than in those who showed early progression (median, 42.31 months; 95% CI, 24.41–NA) (P = .4258). Thirty‐six (60%) patients had grade 3/4 neutropenia. Grade 3/4 febrile neutropenia and infection were recorded during induction (4/60 6.7% and 5/60 8.3% patients, respectively) and maintenance (2/43 4.5% and 4/43 9.1% patients, respectively).
Conclusions
This response‐adapted treatment with RBMD followed by rituximab maintenance is an effective and well‐tolerated salvage treatment for relapsed/refractory follicular lymphoma following first‐line immunochemotherapy.
Clinical trial registration
ClinicalTrials.gov # NCT01133158.
RBMD using a response‐adapted strategy followed by rituximab maintenance is an effective and safe salvage treatment for relapsed/refractory follicular lymphoma following first‐line immunochemotherapy, thereby improving tolerability without compromising efficacy.
Este artículo parte de la hipótesis de que la investigación social que utiliza como herramienta las series de televisión se realiza sin un componente epistemológico robusto, sin variedad metodológica ...y sin amplitud temática. Para comprobar esta hipótesis, se analizan 36 artículos científicos que utilizan como herramienta de investigación social las siguientes series: Breaking Bad, The X Files (Expediente X), Game of Thrones (Juego de Tronos), I Love Lucy, Los Soprano, Mad Men, Orange is The New Black, Sex and the City (Sexo en Nueva York), Star Trek y The West Wing (El Ala Oeste de la Casa Blanca). Finalmente, tras trabajar con una base de 648 registros, se llega a la conclusión de que los artículos analizados sí cuentan con referentes epistemológicos claros, una amplia gama metodológica y abordan gran variedad de temas.
Rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) every 14 days seems to achieve better outcomes than R-CHOP every 21 days in diffuse large B-cell lymphoma (DLBCL) ...patients. Currently, the standard regimen is R-CHOP every 21 days.
This is a phase II clinical trial of treatment with 6 cycles of R-CHOP-14 with pegfilgrastim support in 2 populations of previously untreated DLBCL patients aged ≥65 years (n = 73) or <65 years (n = 51) with low-risk International Prognostic Index scores (0-2).
With a median follow-up of 63.7 months, the 5-year event-free survival rate was 53.8% in patients aged ≥65 years and 71.0% in patients aged <65 years. The 5-year overall survival rate was 71.4 and 89.8%, respectively. The complete remission rate was 69.9% for older and 80.4% for younger patients. The median relative dose intensity of cytotoxic drugs was 143.2% in the elderly and 149.1% in the young patients. Febrile neutropenia was the most common grade 3-4 adverse event, being higher in elderly patients (21.3 vs. 9.3%). Eight deaths (7 in elderly patients) were considered treatment related.
In conclusion, the R-CHOP-14 regimen is feasible and very active, though it is more toxic in elderly patients mainly due to an increased incidence of infections. New strategies, such as new monoclonal antibodies or new targeted therapies, are needed to improve the outcomes of DLBCL patients.
Mosunetuzumab is a CD20 × CD3 T-cell-engaging bispecific monoclonal antibody that redirects T cells to eliminate malignant B cells. In a phase 1 study, mosunetuzumab was well tolerated and active in ...patients with relapsed or refractory B-cell lymphoma. We, therefore, aimed to evaluate the safety and anti-tumour activity of fixed-duration mosunetuzumab in patients with relapsed or refractory follicular lymphoma who had received two or more previous therapies.
We conducted a single-arm, multicentre, phase 2 study at 49 centres in seven countries (Australia, Canada, Germany, South Korea, Spain, UK, and USA). All patients were aged 18 years or older with histologically confirmed follicular lymphoma (grade 1–3a) and an Eastern Cooperative Oncology Group performance status of 0–1. Patients had disease that was relapsed or refractory to two or more previous lines of treatment, including an anti-CD20 therapy and an alkylating agent. Intravenous mosunetuzumab was administered in 21-day cycles with cycle 1 step-up dosing: 1 mg on cycle 1 day 1, 2 mg on cycle 1 day 8, 60 mg on cycle 1 day 15 and cycle 2 day 1, and 30 mg on day 1 of cycle 3 and onwards. Patients with a complete response by investigator assessment using the International Harmonisation Project criteria completed treatment after cycle 8, whereas patients with a partial response or stable disease continued treatment for up to 17 cycles. The primary endpoint was independent review committee-assessed complete response rate (as best response) in all enrolled patients; the primary efficacy analysis compared the observed IRC-assessed complete response rate with a 14% historical control complete response rate in a similar patient population receiving the pan class I PI3K inhibitor copanlisib. Safety was assessed in all enrolled patients. This study is registered with ClinicalTrials.gov, number NCT02500407, and is ongoing.
Between May 2, 2019, and Sept 25, 2020, we enrolled 90 patients. As of the data cutoff date (Aug 27, 2021), the median follow-up was 18·3 months (IQR 13·8–23·3). According to independent review committee assessment, a complete response was recorded in 54 patients (60·0% 95% CI 49·1–70·2). The observed complete response rate was significantly higher than the historical control complete response rate with copanlisib of 14% (p<0·0001), thereby meeting the primary study endpoint. Cytokine release syndrome was the most common adverse event (40 44% of 90 patients) and was predominantly grade 1 (23 26% of 90) and grade 2 (15 17%), and primarily confined to cycle 1. The most common grade 3–4 adverse events were neutropenia or neutrophil count decreased (24 27% of 90 patients), hypophosphataemia (15 17%), hyperglycaemia (seven 8%), and anaemia (seven 8%). Serious adverse events occurred in 42 (47%) of 90 patients. No treatment-related grade 5 (ie, fatal) adverse event occurred.
Fixed-duration mosunetuzumab has a favourable safety profile and induces high rates of complete remissions, allowing potential administration as an outpatient regimen, in patients with relapsed or refractory follicular lymphoma and two or more previous therapies.
F Hoffmann-La Roche and Genentech.
We investigate the binary phase diagram of helium and iron using first-principles calculations. We find that helium, which is a noble gas and inert at ambient conditions, forms stable crystalline ...compounds with iron at terapascal pressures. A FeHe compound becomes stable above 4 TPa, and a FeHe_{2} compound above 12 TPa. Melting is investigated using molecular dynamics simulations, and a superionic phase with sublattice melting of the helium atoms is predicted. We discuss the implications of our predicted helium-iron phase diagram for interiors of giant (exo)planets and white dwarf stars.
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