Mining and analysis of acalabrutinib-induced ADE risk signals based on FDA adverse event reporting system / 中国药房

OBJECTIVE To provide reference for the clinically safe application of acalabrutinib by mining and analyzing the risk signals of adverse drug events （ADE）. METHODS The acalabrutinib-induced ADE reports were extracted from the U.S. FDA adverse event reporting system using the OpenVigil 2.1 platform from November 1， 2017 to March 31， 2023. The reporting odds ratio （ROR） method and composite criteria method from the Medicines and Healthcare Products Regulatory Agency （MHRA） were used for detection of ADE signals. RESULTS There were 7 869 ADE reports of acalabrutinib as the primary suspect drug and 142 ADE positive signals were detected from them， involving 20 system organ classes， which was generally consistent with the ADE recorded in the drug instruction of acalabrutinib， mainly involving general disorders and administration site conditions， various inspection， blood and lymphatic system disorders， various neurological disorders and cardiac disorders. In addition， this study identified several new potential ADE signals that were not mentioned in the drug instruction， including sudden cardiac death， pulmonary toxicity， tumor lysis syndrome， pleural effusion， dyspepsia， gastroesophageal reflux disease， bone pain， decreased blood pressure， and abnormal blood sodium， etc. CONCLUSIONS When using acalabrutinib， in addition to paying attention to the ADE recorded in its instructions， the risk of serious ADE that may lead to death， such as sudden cardiac death and pulmonary toxicity， should also be evaluated to avoid or reduce the occurrence of ADE as much as possible.

Clinical features and prognostic factors of elderly patients with mantle cell lymphoma / 中华血液学杂志

Objective: To examine the clinical characteristics and prognostic factors of elderly patients with mantle cell lymphoma (MCL) and the impact of nutrition and underlying diseases on the prognosis of elderly patients with MCL. Methods: retrospectively analyzed 255 elderly patients with MCL from 11 medical centers, including Peking University Third Hospital between January 2000 and February 2021. We analyzed clinical data, such as age, gender, Mantle Cell Lymphoma International Prognostic Index score, and treatment options, and performed univariate and multivariate prognostic analysis. We performed a comprehensive geriatric assessment on elderly MCL patients with medical records that included retraceable underlying disease and albumin levels, and we investigated the impact of basic nutrition and underlying disorders on MCL prognosis in the elderly. Results: There were 255 senior individuals among the 795 MCL patients. Elderly MCL was more common in males (78.4%), with a median age of 69 yr (ages 65-88), and the majority (88.6%) were identified at a late stage. The 3-yr overall survival (OS) rate was 42.0%, with a 21.2% progression-free survival (PFS) rate. The overall response rate (ORR) was 77.3%, with a 33.3% total remission rate. Elderly patients were more likely than younger patients to have persistent underlying illnesses, such as hypertension. Multivariate analysis revealed that variables related with poor PFS included age of ≥80 (P=0.021), Ann Arbor stage Ⅲ-Ⅳ (P=0.003), high LDH level (P=0.003), involvement of bone marrow (P=0.014). Age of ≥80 (P=0.001) and a high LDH level (P=0.003) were risk factors for OS. The complete geriatric assessment revealed that renal deficiency was associated with poorer OS (P=0.047) . Conclusions: Elderly MCL patients had greater comorbidities. Age, LDH, renal function, bone marrow involvement, and Ann Arbor stage are all independent risk factors for MCL in the elderly.

The Clinical-Biological Features and Prognosis of Patients with Mantle Cell Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To analyze the clinical-biological features and outcomes of patients with mantle cell lymphoma (MCL).@*METHODS@#The clinical and laboratory data of 104 patients with newly diagnosed MCL who were admitted to the Department of Hematology, Fujian Medical University Union Hospital from January 2011 to December 2019 were retrospectively analyzed, and the efficacy was observed through survival analysis.@*RESULTS@#Among 104 MCL patients, 88 were male and 16 were female. The median age was 54 (25-79) years old, 93.0% (93/100) of the patients with advanced stage (III and IV stages) and 48.08% (50/104) of the patients with bone marrow infiltration. Patients with Ki-67≥50% had higher WBC counts and LDH levels. Univariate analysis showed that the patients with WBC≥15×109/L, bone marrow involvement, high LDH, high β2-MG levels, Ki-67≥50%, SOX11-, had lower OS and EFS rates (P =0.005, 0.049, 0.033, 0.025, 0.042, 0.018 and 0.001, 0.021, 0.024, 0.035, 0.014, 0.026). The OS rate and EFS rate of patients in R-CHOP and R-Hyper-CVAD treatment groups were significantly higher than those in other treatment groups (P =0.02, 0.002 and P =0.001, 0.001). Patients with autologous stem cell transplantation (ASCT) had higher OS rate and EFS rate (P =0.037, 0.013). Multivariate COX analysis showed that only WBC count, SOX11 expression and whether achieved CR after 4 courses treatment were the independent factors affecting the prognosis.@*CONCLUSION@#MCL mainly occur in elderly men. There are many factors affecting patients' survival, while WBC≥15×109/L, negative expression of SOX11 and failure to achieve CR after 4 courses of treatment are adverse factors for MCL patients.

Comprehensive Diagnosis of Mantle Cell Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To explore the value of multiple detection methods based on histopathology and supplemented by bone marrow or peripheral blood sample detections in the comprehensive diagnosis of mantle cell lymphoma (MCL).@*METHODS@#The clinical, immunophenotypic, pathologic, cytogenetic and molecular features of 153 newly diagnosed MCL patients admitted to the hematology department of our hospital from May 2009 to September 2022 were analyzed.@*RESULTS@#144 (96.6%) of the 149 MCL patients who underwent marrow or peripheral blood IGH/CCND1 FISH detection at initial diagnosis were positive, of which 36 cases (24.2%) had a low proportion positive. The immunophenotypes in 115 patients were analyzed by flow cytometry (FCM), 89 cases (77.4%) conformed to MCL while 23 cases (20.0%) were initially diagnosed as B-cell lymphoproliferative disorders (B-LPD). Of the 75 cases who performed bone marrow biopsy, 50 cases (66.7%) had morphological and immunophenotypic characteristics consistent with MCL, 15 cases (20.0%) were classified as B-LPD, and 10 cases with no obvious abnormality. 77 patients underwent histopathology examination, of which 73 cases (94.8%) had typical clinicopathological features of MCL, including 2 CCND1 negative MCL, 2 pleomorphic variants, 5 pleomorphic variants and 4 cases diagnosed as other leukemia or lymphoma. Among 153 cases of MCL, 128 cases were classic MCL(cMCL), and another 25 cases (16.3%) were diagnosed as leukemic non-lymph node MCL (lnnMCL). The incidence of IGHV mutation, TP53 mutation and CD23 expression positive were significantly different between cMCL and lnnMCL.@*CONCLUSION@#Histopathology is still the main standard for the diagnosis of cMCL, and detection based on bone marrow or peripheral blood samples is an important means for the diagnosis of lnnMCL. Single marker or examination can cause a certain proportion of misdiagnosis. The accurate diagnosis of MCL depends on a combination of multiple detection methods.

Mantle Cell Lymphona Masquerading as Obstructive Sleep Apnoea

@#Tonsillar malignancy typically presents with asymmetrical tonsillar enlargement, lesion on the tonsils, sore throat or a neck mass. We report a case of unsuspected tonsillar malignancy in a 56-year-old gentleman who presented with symptoms of obstructive sleep apnoea. His tonsils were grade III bilaterally with normal mucosa. Tonsillectomy was performed to improve patient’s compliance with Continuous Positive Airway Pressure (CPAP) therapy. These tonsillar specimens were reported to be Mantle Cell Lymphoma (MCL) based on the histology and ancillary studies. This case highlights that benign-looking symmetrical tonsillar enlargement can harbour occult malignancy. It is important to note that OSA symptoms may be the presentation for haematological malignancies. Tonsillar specimens should be sent for histopathological examination regardless of the indication to avoid misdiagnosis and delay in treatment.

Inhibidores de bruton tirosina quinasa. ¿Qué necesita saber el oncohematólogo y el cardiólogo? / Bruton tyrosine kinase inhibitors. What does the oncohematologist and the cardiologist need to know?

Resumen Los avances en el conocimiento incorporados en la última década han modificado en gran parte el paradigma del tratamiento de las enfermedades hematológicas malignas. Particularmente la intro ducción de los inhibidores de la Bruton tirosina quinasa (iBTK) y otras drogas blanco junto a nuevos anticuerpos monoclonales se han transformado en los agentes de elección, tanto para la leucemia linfática crónica (LLC) como para otros linfomas "B" periféricos como el linfoma de células del manto (LCM). Los resultados de eficacia frente a la terapia genotóxica son tan exitosos que el fin de la quimio inmunoterapia, sobre todo para la LLC, es ya un postulado reconocido por los principales grupos de investigación. Por otra parte, los nuevos fármacos modificaron el perfil de eventos adversos lo que obligó al desarrollo de nuevas subespecialidades como la cardio-oncología, la cual constituye actualmente un baluarte para el manejo racional de estos pacientes. La presente revisión tiene como objetivo destacar el estado actual del conocimiento sobre estas enfermedades, los principios farmacológicos junto a los nuevos eventos adversos de los iBTK y el invalorable aporte de la cardiología para un correcto tratamiento y control de estos pacientes.

Abstract Advances in knowledge incorporated in the last decade have modified the treatment paradigm in most of the malignant hematological diseases. In particular, the introduction of Bruton tyrosine kinase inhibitors (BTKi) and other target drugs together with new monoclonal antibodies have become agents of choice for both chronic lym phocytic leukemia (CLL) and other peripheral "B" lymphomas such as mantle cell lymphoma (MCL). The results of efficacy against genotoxic therapy are so successful that the end of chemoimmunotherapy, especially for CLL, is already a postulate recognized by the main research groups. On the other hand, the new drugs modified the profile of adverse events, which forced the development of new subspecialties such as cardio-oncology, which currently constitutes a bastion for the rational management of these patients. This review aims to highlight the current state of knowledge on these pathologies, pharmacological principles together with new adverse events of iBTK and the invaluable contribution of cardiology for correct management of these patients.

Lymphomatous Polyposis: Case Report and Literature Review / Poliposis linfomatosa: reporte de caso y revisión de la literatura

Abstract Lymphomatous polyposis (LP) is the endoscopic feature of primary gastrointestinal mantle cell lymphoma (MCL), a rare type of B-cell non-Hodgkin's lymphoma (NHL) and a typical but rare endoscopic pattern of gastrointestinal tract involvement (GIT) by nodal MCL. We present the case of a 62-year-old man with nodal MCL, with LP as a manifestation of GIT, and review the literature.

Resumen La poliposis linfomatosa (PL) es la característica endoscópica del linfoma de células del manto (LCM) gastrointestinal primario, un tipo infrecuente de linfoma no Hodgkin (LNH) de células B, así como un patrón endoscópico típico, pero infrecuente, del compromiso del tracto gastrointestinal (TGI) por LCM nodal. Presentamos el caso de un hombre de 62 años con LCM nodal, con PL como manifestación del compromiso gastrointestinal, y realizamos una revisión de la literatura.

Clinical and laboratory diagnosis of indolent leukemic mantle cell lymphoma: report of one case and review of literature / 白血病·淋巴瘤

Objective:To improve the understanding of indolent mantle cell lymphoma (MCL).Methods:The data of a patient with indolent leukemic MCL in the Second Affiliated Hospital of Nanjing Medical University in May 2013 were collected. The cell morphology was analyzed by using cell smear, the flow cytometry was used to make immunophenotype analysis, the karyotype analysis was performed by usig cytogenetic technique, and polymerase chain reaction (PCR) was used to make the immunoglobulin gene analysis. At the same time, lymph node pathology and immunohistochemistry were also analyzed. The related articles published were reviewed to sum up the characteristics and the treatment of indolent MCL.Results:The male patient aged 60 years was obviously asymptomatic accompanied with slow disease progression, leukemic manifestation and without lymphadenopathy. He received pathological biopsy because of located lymphadenopathy in 2008. Small cell morphology, Kappa light chain immunophenotype, t(11;14) translocation showed after the cytogenetic examination, clonal immune globulin gene rearrangement and low Ki-67 positive index were identified. In situ MCL was diagnosed by retrospective pathology.Conclusions:Indolent MCL is extremely rare. It is typically asymptomatic with none or minimal nodal involvement, indolent disease course, leukemic phase with mild lymphocytosis, Kappa light chain expression, simple karyotype, classical or small cell morphology of tumor cells and the positive index of Ki-67 <10%. In situ MCL can be seen in pathology examination. IgVH gene mutation positive and SOX11 negative expression are notable in indolent MCL. International prognostic index of MCL is probably not appropriate in the prognostic analysis of leukemic indolent MCL. It is emphasized that initial observation and having therapies only after the disease progression can be suited for indolent MCL.

Linfomas en la era COVID-19 / Lymphoma and COVID-19

Resumen El coronavirus 2 del síndrome respiratorio agudo grave (SARS-CoV-2) y su traducción clínica, la enfermedad por coronavirus 2019 (COVID-19), representan una enfermedad con manifestaciones respiratorias potencialmente fatales. Actualmente existen aproximadamente 12,700,000 personas afectadas por esta virus, el cual ha ocasionado 561,517 muertes en el mundo. Los pacientes con diagnóstico de linfoma, al igual que otros pacientes con cáncer activo, presentan compromiso inmunitario, ya sea por su propia patología o debido al tratamiento que reciben, por lo que son especialmente susceptibles a desarrollar cuadros graves de COVID-19. La transmisión comunitaria del SARS-CoV-2 dificulta el acceso al sistema de salud y, por ende, el seguimiento estricto que requieren lo pacientes bajo tratamiento oncológico. En la etapa en la que nos encontramos actualmente, la transmisión global de la infección por SARS-CoV-2 continúa en ascenso, por lo que un control epidemiológico cercano es poco probable. Ante este contexto, surge la necesidad de establecer guías de tratamiento de pacientes con neoplasias hematológicas.

Abstract The SARS-CoV-2 virus and its clinical translation COVID-19 represent a disease with potentially fatal respiratory manifestations. Currently, there are approximately 12,700,000 people affected by this virus, which has caused 561,517 deaths worldwide. Patients with a diagnosis of lymphoma, like other patients with active cancer, have immune compromise either due to their own pathology or due to the treatment they receive, making them especially susceptible to developing severe cases of COVID-19. The community transmission of SARS-CoV-2 hinders access to the health system and, therefore, the strict monitoring required by patients undergoing cancer treatment. At the stage we are currently in, global transmission of SARS-CoV-2 infection continues to rise, making close epidemiological control unlikely. In this context, the need arises to establish guidelines for the treatment of patients with hematological malignancies.

Bruton tyrosine kinase inhibitors and refractory mantle cell lymphoma / 中国临床药理学与治疗学

Bruton tyrosine kinase (BTK) is a key mediator of B-cell receptor signalling cascade and an effective target for treating mantle cell lymphoma (MCL). BTK inhibitors play a critical role in the treatment of MCL. Here we introduced the mechanism of action of BTKI in the treatment of MCL. Though generally well prescribed, Ibrutinib, as the first BTKI, still has limitations of toxicity and resistance. New BTK inhibitors, such as zanubrutinib, acalabrutinib and orelabrutinib, are designed to improve on the safety and efficacy as first-generation BTK inhibitors. Comparing the similarities and differences of the two generations of BTKI in structure and function provides a basis for better clinical application of BTKI. On November 15, 2019, FDA approved zanubrutinib for marketing for patients with adult mantle cell lymphoma. Compared with Ibrutinib, zanubrutinib was found with higher target selectivity, longer-lasting inhibition, fewer adverse reactions, and better patient benefit. Zanubrutinib provides a viable treatment option for patients with r/r MCL. At the same time, it is also actively carrying out clinical researches on the treatment of other B-cell lymphomas. It is a very promising targeted drug.

Mantle cell lymphoma relapsed after autologous stem cell transplantation: a single-center experience

BACKGROUND: Autologous stem cell transplantation (autoSCT) can extend remission of mantle cell lymphoma (MCL), but the management of subsequent relapse is challenging.METHODS: We examined consecutive patients with MCL who underwent autoSCT at Veterans Affairs Puget Sound Health Care System between 2009 and 2017 (N=37).RESULTS: Ten patients experienced disease progression after autoSCT and were included in this analysis. Median progression free survival after autoSCT was 1.8 years (range, 0.3–7.1) and median overall survival after progression was only 0.7 years (range, 0.1 to not reached). The 3 patients who survived more than 1 year after progression were treated with ibrutinib.CONCLUSION: Our findings suggest that ibrutinib can achieve relatively prolonged control of MCL progressing after autoSCT.

Chimeric antigen receptor T-cell therapy: a promising treatment modality for relapsed/refractory mantle cell lymphoma / 医学前沿

Mantle cell lymphoma (MCL) is a distinct histological type of B-cell lymphoma with a poor prognosis. Several agents, such as proteasome inhibitors, immunomodulatory drugs, and inhibitors of B cell lymphoma-2 and Bruton's tyrosine kinase have shown efficacy for relapsed or refractory (r/r) MCL but often have short-term responses. Chimeric antigen receptor (CAR) T-cell therapy has emerged as a novel treatment modality for r/r non-Hodgkin's lymphoma. However, long-term safety and tolerability associated with CAR T-cell therapy are not defined well, especially in MCL. In this report, we described a 70-year-old patient with r/r MCL with 48-month duration of follow-up who achieved long-term remission after CAR T-cell therapy. CAR T-cell-related toxicities were also mild and tolerated well even in this elderly patient. This report suggested that CAR T-cell therapy is a promising treatment modality for patients with MCL, who are generally elderly and have comorbid conditions.

Demencia Rápidamente Progresiva Como Manifestación De Recaída En Linfoma De Células Del Manto: Experiencia En Diagnóstico Y Tratamiento / Rapidly Progressive Dementia As A Manifestation Of Relapse In Mantle Cell Lymphoma: Experience In Diagnosis And Treatment

Resumen Introducción: La demencia rápidamente progresiva es una entidad que tiene una etiología múltiple y heterogénea. Se caracteriza por la alteración de dos o más dominios cognitivos en un periodo menor de 1 a 2 años. El compromiso del sistema nervioso central por el linfoma de células del manto es poco frecuente, de mal pronóstico y debuta principalmente en las fases tardías de la enfermedad como una recaída. Caso Clínico: Varón de 61 años con antecedente de linfoma de células del manto quien presenta una recaída asociada al sistema nervioso central que debuta como demencia rápidamente progresiva y se confirma por estudios de citometría de flujo en líquido cefalorraquídeo. Presenta una adecuada respuesta al manejo con un inhibidor de la tirosina quinasa (Ibrutinib), resolviendo la sintomatología clínica y los hallazgos imagenológicos. Discusión: El compromiso del sistema nervioso central secundario al linfoma de células del manto es una complicación poco frecuente y debuta como una recaída con manifestaciones clínicas variables que requieren de una intervención oportuna con el objetivo de mejorar la supervivencia del paciente. La terapia con un agente único como el Ibrutinib parece ser una buena opción en casos de refractariedad y compromiso neurológico.

Abstract Introduction: Rapidly progressive dementia is an entity that has a multiple and heterogeneous etiology. It is characterized by the alteration of two or more cognitive domains in a period of less than 1 to 2 years. The involvement of the central nervous system attributed to mantle cell lymphoma is rare with a poor prognosis and mainly debuts in the late stages of the disease as a relapse. Case Report: A 61-year-old male with a history of mantle cell lymphoma who presents a relapse of the central nervous system, given by a clinical course compatible with a rapidly progressive dementia and which is confirmed by flow cytometry studies in cerebrospinal fluid. It presents an adequate response to management with a tyrosine kinase inhibitor (Ibrutinib), resolving clinical symptoms and imaging findings. Discussion: The involvement of the central nervous system secondary to mantle cell lymphoma is a rare complication and debuts as a relapse with variable clinical manifestations that requires a timely intervention with the aim of improving patient survival. Therapy with a single agent such as Ibrutinib seems to be a good alternative in cases of refractoriness and neurological involvement.

Characteristics of follicular and mantle cell lymphoma in Brazil: prognostic impact of clinical parameters and treatment conditions in two hospitals

ABSTRACT Objective: Follicular and mantle cell lymphoma are low-grade B-cell malignancies that lack good responses to chemoimmunotherapy. This study aimed to assess retrospectively clinicopathological features and to determine independent prognostic factors for follicular and mantle cell lymphoma patients treated at two Brazilian medical centers: the Hematology and Hemotherapy Center of the Universidade Estadual de Campinas (Unicamp), a public university hospital, and AC. Camargo Cancer Center, a specialized cancer center. Methods: Two hundred and twenty-seven follicular and 112 mantle cell lymphoma cases were diagnosed between 1999 and 2016. Archived paraffin blocks were retrieved and reviewed. Corresponding demographics and clinical data were recovered from medical charts. Outcome analyses considered both overall and event-free survival. Results: For follicular lymphoma treated with the R-CHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, prednisone) and R-CVP (rituximab, cyclophosphamide, vincristine sulfate, prednisone) regimens, both B-symptoms (p-value < 0.01 for overall and event-free survival) and high-risk Follicular Lymphoma International Prognostic Index (p-value < 0.01 for overall survival) were independently associated to worse prognosis. Maintenance with rituximab improved the prognosis (p-value < 0.01 for overall survival). For mantle cell lymphoma, B-symptoms (p-value = 0.03 for overall survival and event-free survival) and bone marrow infiltration (p-value = 0.01 for overall survival) independently predicted reduced survival, and rituximab at induction increased both event-free and overall survival (p-value < 0.01 in both analyses). Combinations of these deleterious features could identify extremely poor prognostic subgroups. The administration of rituximab was more frequent in the AC. Camargo Cancer Center, which was the institution associated with better overall survival for both neoplasias. Conclusion: This study represents the largest cohort of follicular and mantle cell lymphoma in South America thus far. Some easily assessable clinical variables were able to predict prognosis and should be considered in low-income centers. In addition, the underuse of rituximab in the Brazilian public health system should be reconsidered in future health policies.

Metástasis mamaria de linfoma de células del manto / Mammary metastasis of mantle cell lymphoma

Resumen ANTECEDENTES: Los linfomas mamarios primarios constituyen menos de 1% de todos los linfomas no-Hodgkin, 1.7-2.2% de todos los linfomas no-Hodgkin nodales adicionales y 0.04-0.5% de todas las neoplasias malignas de la mama. El linfoma de células del manto representa 4% de los linfomas en Estados Unidos, y entre 7-9% en Europa y se diagnostica en pacientes con una mediana de edad de 60 años. Aparece en mujeres posmenopáusicas en forma de masa mamaria indolora, unilateral. El linfoma de mama secundario es sistémico, con afectación simultánea o posterior en otro sitio. CASO CLÍNICO: Paciente con una tumoración mamaria, inicialmente postraumática, que en el contexto de plaquetopenia se catalogó clínica y radiológicamente como hematoma y que, más tarde, el diagnóstico fue: linfoma de células del manto secundario a linfoma previo nodal inguinal en segunda línea de tratamiento con quimioterapia. CONCLUSIONES: La persistencia o el rápido crecimiento de un hematoma mamario o de una lesión con apariencia radiológica benigna, sobre todo con antecedente de linfoma previo, puede resultar maligna. La biopsia mediante aguja gruesa es decisiva en el diagnóstico porque permite el estudio histológico e inmunohistoquímico para la confirmación molecular. El tratamiento se basa, sobre todo, en quimio y radioterapia, opciones que mejoran la supervivencia y disminuyen la recurrencia.

Abstract BACKGROUND: Primary mammary lymphomas represent less than 1% of all Non Hodgking Lymphomas (NHL). Mantle cell lymphoma (MCL) represents 4% of lymphomas in the United States, and 7-9% in Europe and is diagnosed in patients with a median age of 60 years. Unilateral painless mammary mass in postmenopausal women use to be the clinical presentation. Secondary breast lymphoma is defined as the presence of systemic lymphoma with breast involvement, as the patient below. CLINICAL CASE: 57-year-old female patient with post-traumatic mammary tumor, with history of thrombocytopenia, first-time diagnosed of hematoma, with breast enlargement and later diagnosed as lymphoma of mantle cells with pathology test and classified as secondary to previous inguinal nodal lymphoma. CONCLUSIONS: It is important to keep in mind this diagnosis in view of the persistence or rapid growth of a mammary hematoma or other lesion with benign radiological appearance. The biopsy is the gold standard for diagnosis, since it allows the histological and immunohistochemical study, for molecular confirmation. The treatment is mainly based on chemo / radiotherapy, which improves survival and decreases recurrence.

Prognostic significance of miRNA-223 targeting SOX11 in mantle cell lymphoma / 中华血液学杂志

Objective@#To explore the expression and prognostic significance of miR-223 in patients with mantle cell lymphoma (MCL) and to investigate the possible mechanism.@*Methods@#Twenty-one newly diagnosed MCL patients with bone marrow involvement were enrolled in the present study, 20 healthy donors as normal control. The expression level of miR-223 and SOX11 mRNA was determined by RQ-PCR. CCK-8 and flow cytometer assays were used to analyze cell proliferation, cell cycle and apoptosis of the constructed miR-223 overexpressing MCL cell line, Granta519 cells. SOX11 protein expression level was determined by Western blot. The target gene of miR-223 was confirmed by dual luciferase reporter assay.@*Results@#①Of the 21 newly diagnosed MCL patients, 15 were male and 6 female, the median age was 58 (37-72) years. The expression level of miR-223 was significantly down regulated in MCL patients compared with that of healthy donors (14.7±10.5 vs 1 244.1±1 935.2, P<0.001). The lower expression of miR-223 was inversely correlated with high-risk mantle international prognostic index (P=0.001), elevated LDH (P=0.001), ECOG score ≥2 (P=0.035). ②Using the median relative expression level of miR-223 as the cutoff value, 21 MCL patients were divided into high-expression group (n=10) and low-expression group (n=11) and found that the high-expression group had a significantly superior OS (median OS: 36 vs 12 months, P=0.021). ③In vitro results showed that compared with the control group, the proliferation of miR-223 overexpressed Granta519 cells was inhibited (the most significant reduction on 96h, P<0.001), manifested by lower proportion of cells in G2/M phase (P<0.001) and increased apoptosis (P<0.001), and the expression level of SOX11 protein in Granta519 cells was significantly lower than that of the control group. ④miR-223 could inhibited the 3′ untranslated region of SOX11, and the expression level of miR-223 was significantly negatively correlated with mRNA level of SOX11 in MCL patients (r=-0.81, P<0.001).@*Conclusions@#The expression of miR-223 was repressed in MCL and was associated with poor clinical outcomes, which may be probably attributed to its direct targeting SOX11.

Prognostic significance of miRNA-223 targeting SOX11 in mantle cell lymphoma / 中华血液学杂志

Objective: To explore the expression and prognostic significance of miR-223 in patients with mantle cell lymphoma (MCL) and to investigate the possible mechanism. Methods: Twenty-one newly diagnosed MCL patients with bone marrow involvement were enrolled in the present study, 20 healthy donors as normal control. The expression level of miR-223 and SOX11 mRNA was determined by RQ-PCR. CCK-8 and flow cytometer assays were used to analyze cell proliferation, cell cycle and apoptosis of the constructed miR-223 overexpressing MCL cell line, Granta519 cells. SOX11 protein expression level was determined by Western blot. The target gene of miR-223 was confirmed by dual luciferase reporter assay. Results: ①Of the 21 newly diagnosed MCL patients, 15 were male and 6 female, the median age was 58 (37-72) years. The expression level of miR-223 was significantly down regulated in MCL patients compared with that of healthy donors (14.7±10.5 vs 1 244.1±1 935.2, P<0.001). The lower expression of miR-223 was inversely correlated with high-risk mantle international prognostic index (P=0.001), elevated LDH (P=0.001), ECOG score ≥2 (P=0.035). ②Using the median relative expression level of miR-223 as the cutoff value, 21 MCL patients were divided into high-expression group (n=10) and low-expression group (n=11) and found that the high-expression group had a significantly superior OS (median OS: 36 vs 12 months, P=0.021). ③In vitro results showed that compared with the control group, the proliferation of miR-223 overexpressed Granta519 cells was inhibited (the most significant reduction on 96h, P<0.001), manifested by lower proportion of cells in G2/M phase (P<0.001) and increased apoptosis (P<0.001), and the expression level of SOX11 protein in Granta519 cells was significantly lower than that of the control group. ④miR-223 could inhibited the 3' untranslated region of SOX11, and the expression level of miR-223 was significantly negatively correlated with mRNA level of SOX11 in MCL patients (r=-0.81, P<0.001). Conclusions: The expression of miR-223 was repressed in MCL and was associated with poor clinical outcomes, which may be probably attributed to its direct targeting SOX11.

CAR-NK-92MI and CAR-CD19-T cells targeting CD19 antigen exhibit significant in vitro killing activity on mantle cell lymphoma / 中国肿瘤生物治疗杂志

@#[Abstract] Objective: To investigate the in vitro cytotoxicity of the chimeric antigen receptor-modified T cells and NK-92MI cells (CAR-NK-92MI cells) and CAR-CD19-T cells against mantle cell lymphoma (MCL). Methods: CAR-T cell technology, successfully obtained in clinical trial of B-lineage acute lymphoblastic leukemia (B-ALL) treatment, was used in this study. In the case of high expression of CD19 antigen in MCL, CAR- CD19-T cells and CAR- CD19-NK-92MI cells targeting CD19 antigen were generated, respectively. Then, their cytotoxicity against MCL cell lines was detected by LDH release assay and the results were verified by flow cytometry. Results: Compared with control group, both CAR-NK-92MI and CAR-CD19-T cells exhibited prominent killing effect against MCLcells（all P<0.01）; in addition, the two CAR cells exhibited high cytotoxicity against K562-CD19 cells but not on K562 cells（all P <0.01）. The death rate of MCL cells from CAR-NK-92MI group was 30%-40% more than that of control group, and the death rate of MCL from CAR-CD19-T group was 40%-50% more than that of control group. Conclusion: Both CAR-NK-92MI and CAR-CD19-T cells exhibited potent cytotoxicity against MCLcells in vitro.

Mantle Cell Lymphoma-A Retrospective 2-Year Study

Materials and methods Retrospective study for period of 2 years was conducted. For this study, we reviewed bone marrow material along with nodal and extranodal tissues. There were 16 cases of mantle cell lymphoma (MCL). Each patient had an absolute lymphocyte count of more than 10 × 109/l at the time of initial evaluation at our institution. Giemsa stained peripheral blood and bone marrow aspirate smears were reviewed, along with haematoxylin-eosin-stained histologic sections of bone marrow aspiration and core biopsy specimens. The immuno-phenotype of the neoplastic cells supported the diagnosis of MCL. The clinical and pathological spectrum will be discussed. Immuno-histochemistry Immuno-histochemical staining for CD3, CD20, CD23, CD1O, KI67 CYCLIN D1 were performed on formalin-fixed, paraffin-embedded tissue sections of either bone marrow aspirate or core biopsy tissue sections in all 16 cases. Results There were 11 men and 5 women with a median age of 68 years (range, 40–74 years). Physical examination revealed splenomegaly in 15 out of 16 patients. Lymphadenopathy involving multiple sites was present in 10 patients. Conclusion MCL can exhibit a wide spectrum of morphologic findings. We suggest that cell size and chromatin characteristics are useful for dividing these cases into two groups: small cell and large/blastoid. The large/blastoid group predicts poorer prognosis and includes cases with large cells, many of which are nucleolated and resemble prolymphocytes, as well as blastoid cells that resemble lymphoblasts. In this study, a cut-off of at least 20% large/blastoid cells best predicted poorer survival.

Progress in treatment of mantle cell lymphoma / 白血病·淋巴瘤

Mantle cell lymphoma (MCL), being a kind of aggressive non-Hodgkin ' s lymphoma (NHL), accounts for 6 % - 8 % of NHL in adults which is characterized by malignant B cell infiltration of lymph node, gastrointestinal tract and bone marrow. MCL commonly responds to initial therapy but inevitably occurs relapse and drug resistance. The study on MCL in the 58th American Society of Hematology Annual Meeting has covered many aspects such as basic research, clinical treatment and new drug research. The development of novel mouse model and the exploration of signaling pathways provide a basis for the improvement of MCL pathogenesis and new drug research. VcR-CVAD, VCR and some other chemotherapy regimens designed for different patients have showed satisfactory results. New drugs such as inhibitors of CDK, PI3K and bcl-2 in initial clinical trials are also promising. IACS-010759 and other small molecules provide new directions for the treatment of MCL.